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Showing 422 matching result(s) | Selected target(s): 0
| SELECT | TARGET ID | TARGET NAME | UNIPROT AC | UNIPROT ID | SYNONYMS | FUNCTION | CLASS | SUBCLASS | MAX PHASE | ICD CHAPTERS LIST SUCCESSFUL | ICD CHAPTERS NUM SUCCESSFUL | ICD CHAPTERS LIST CLINICAL | ICD CHAPTERS NUM CLINICAL | STRUCTURE INFO | SOURCE | STRUCTURE | LIGANDS | BS COORDINATES |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D0001 | Arachidonate 5-lipoxygenase | P09917 | LOX5_HUMAN | LOG5, 5-lipoxygenase, 5-LO | Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes. | Enzyme | Oxidoreductase | Successful | ['01 Certain infectious or parasitic diseases', '12 Diseases of the respiratory system'] | 2 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '03 Diseases of the blood or blood-forming organs', '05 Endocrine, nutritional or metabolic diseases', '12 Diseases of the respiratory system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 8 | Downloaded from PDB (6N2W) | 6N2W |
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Go to ligands | 36.3700 66.3600 38.9600 | |
| D0002 | Diacylglycerol acyltransferase 1 | O75907 | DGAT1_HUMAN | Retinol O-fatty-acyltransferase, Diglyceride acyltransferase, Diacylglycerol O-acyltransferase 1, DGAT, Acyl-CoA retinol O-fatty-acyltransferase, ARAT, AGRP1, ACAT-related gene product 1 | Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. In contrast to DGAT2 it is not essential for survival. May be involved in VLDL (very low density lipoprotein) assembly. In liver, plays a role in esterifying exogenous fatty acids to glycerol. Functions as the major acyl-CoA retinol acyltransferase (ARAT) in the skin, where it acts to maintain retinoid homeostasis and prevent retinoid toxicity leading to skin and hair disorders. | Enzyme | Transferase | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['01 Certain infectious or parasitic diseases', '05 Endocrine, nutritional or metabolic diseases'] | 2 | Downloaded from PDB (6VP0) | 6VP0 |
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Go to ligands | 113.8100 88.9400 117.5800 | |
| D0003 | Caspase-1 | P29466 | CASP1_HUMAN | P45, Interleukin-1 beta-converting enzyme, Interleukin-1 beta converting enzyme, Interleukin-1 beta convertase, IL1BCE, IL1BC, IL-1BC, IL-1 beta-converting enzyme, IL-1 beta converting enzyme, ICE, CASP-1 | Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis. Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive. Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system'] | 4 | Downloaded from PDB (6F6R) | 6F6R |
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Go to ligands | 4.0200 30.2800 1.7600 | |
| D0004 | PAK-4 protein kinase | O96013 | PAK4_HUMAN | p21-activated kinase 4, Serine/threonine-protein kinase PAK 4, PAK-4, KIAA1142 | Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN. Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5ZJW) | 5ZJW |
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Go to ligands | -5.7200 -5.5500 18.8600 | |
| D0005 | Thymidylate synthase | P04818 | TYSY_HUMAN | TSase, TS | Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (1HVY) | 1HVY |
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Go to ligands | 0.5000 11.4900 15.4500 | |
| D0006 | Aggrecanase | Q9UNA0 | ATS5_HUMAN | Aggrecanase-2, ADMP-2, ADAMTS5, ADAMTS-5, ADAM-TS5, ADAM-TS 5, ADAM-TS 11, A disintegrin and metalloproteinase with thrombospondinmotifs 5 | Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. May play a role in proteolytic processing mostly during the peri-implantation period. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['15 Diseases of the musculoskeletal system or connective tissue'] | 1 | Downloaded from PDB (3HYG) | 3HYG |
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Go to ligands | 13.6900 1.9100 -2.5700 | |
| D0007 | Presenilin 2 | P49810 | PSN2_HUMAN | STM2, STM-2, Presenilin-2, PSNL2, PS-2, E5-1, AD5, AD4, AD3LP | Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. May function in the cytoplasmic partitioning of proteins. The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is involved in calcium homeostasis. Is a regulator of mitochondrion-endoplasmic reticulum membrane tethering and modulates calcium ions shuttling between ER and mitochondria. Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['15 Diseases of the musculoskeletal system or connective tissue'] | 1 | Downloaded from PDB (7Y5X) | 7Y5X |
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Go to ligands | 99.9400 119.2700 99.8300 | |
| D0008 | MAP kinase signal-integrating kinase 2 | Q9HBH9 | MKNK2_HUMAN | Mnk2, MAPK signal-integrating kinase 2 | Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6CJ5) | 6CJ5 |
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Go to ligands | 7.4900 55.5600 11.8700 | |
| D0009 | Metabotropic glutamate receptor 5 | P41594 | GRM5_HUMAN | MGLUR5, GPRC1E | G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '20 Developmental anomalies', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 4 | Downloaded from PDB (6FFI) | 6FFI |
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Go to ligands | -23.9900 -5.9600 42.8200 | |
| D0010 | Gamma-secretase | Q96BI3+Q9NZ42+P49768+Q92542 | APH1A_HUMAN+APH1B_HUMAN+PEN2_HUMAN+NICA_HUMAN+PSN1_HUMAN | Presenilin-stabilization factor-like, PSFL, Aph-1beta | Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex. Probably present in a minority of gamma-secretase complexes compared to APH1A. | Enzyme | Hydrolase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '15 Diseases of the musculoskeletal system or connective tissue'] | 5 | Downloaded from PDB (7D8X) | 7D8X |
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Go to ligands | 164.3600 172.7000 148.7800 | |
| D0011 | Carbonic anhydrase XII | O43570 | CAH12_HUMAN | Tumor antigen HOM-RCC-3.1.3, Carbonic anhydrase 12, Carbonate dehydratase XII | Reversible hydration of carbon dioxide. | Enzyme | Lyase | Successful | ['01 Certain infectious or parasitic diseases', '14 Diseases of the skin'] | 2 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6G5L) | 6G5L |
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Go to ligands | 24.8100 3.8100 10.8800 | |
| D0012 | Dihydrofolate reductase | P00374 | DYR_HUMAN | DYR, DHFRP1 | Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2. Key enzyme in folate metabolism. | Enzyme | Oxidoreductase | Successful | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '13 Diseases of the digestive system', '16 Diseases of the genitourinary system'] | 4 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '12 Diseases of the respiratory system', '15 Diseases of the musculoskeletal system or connective tissue'] | 4 | Downloaded from PDB (1KMV) | 1KMV |
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Go to ligands | 13.6900 24.4400 32.6200 | |
| D0013 | Matrix metalloproteinase-8 | P22894 | MMP8_HUMAN | PMNL-CL, PMNL collagenase, Neutrophil collagenase, CLG1 | Can degrade fibrillar type I, II, and III collagens. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['15 Diseases of the musculoskeletal system or connective tissue'] | 1 | Downloaded from PDB (4QKZ) | 4QKZ |
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Go to ligands | 7.4700 12.0700 22.2600 | |
| D0014 | Voltage-gated potassium channel Kv1.5 | P22460 | KCNA5_HUMAN | Voltage-gatedpotassium channel subunit Kv1.5, Voltage-gated potassium channel subunit Kv1.5, Voltage-gated potassium channel HK2, Potassium voltage-gated channel subfamily A member 5, Potassium channel Kv1.5, HPCN1, HK2, 02-Sensitive Potassium Channel Kv1.5 | Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well, channel properties depend on the type of alpha subunits that are part of the channel. Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. Homotetrameric channels display rapid activation and slow inactivation. May play a role in regulating the secretion of insulin in normal pancreatic islets. Isoform 2 exhibits a voltage-dependent recovery from inactivation and an excessive cumulative inactivation. Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. | Ion Channel | Channels/pores | Successful | ['11 Diseases of the circulatory system'] | 1 | ['11 Diseases of the circulatory system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 2 | Modelled with AlphaFold (AF-P22460-F1-model_v4) | Ab initio |
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Go to ligands | 10.9700 7.1100 1.8700 | |
| D0015 | Urokinase-type plasminogen activator | P00749 | UROK_HUMAN | UPA, U-plasminogen activator | Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. | Enzyme | Hydrolase | Successful | ['03 Diseases of the blood or blood-forming organs', '11 Diseases of the circulatory system'] | 2 | ['02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '13 Diseases of the digestive system', '22 Injury, poisoning or certain other consequences of external causes'] | 5 | Downloaded from PDB (1C5Y) | 1C5Y |
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Go to ligands | 8.4500 -1.4300 24.3800 | |
| D0016 | MEK kinase kinase 1 | Q92918 | M4K1_HUMAN | Mitogen-activated protein kinase kinase kinase kinase 1, MEKKK 1, MAPK/ERK kinase kinase kinase 1, Hematopoietic progenitor kinase, HPK1 | Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate. Serine/threonine-protein kinase, which may play a role in the response to environmental stress. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (7R9N) | 7R9N |
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Go to ligands | -42.2100 -73.2600 262.1800 | |
| D0017 | Fyn tyrosine protein kinase | P06241 | FYN_HUMAN | Tyrosine-protein kinase Fyn, Src-like kinase, SLK, Proto-oncogene tyrosine-protein kinase Fyn, Proto-oncogene c-Fyn, Proto-oncogene Syn, Fyn p59-Fyn, Fyn Protooncogene Syn | Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Phosphorylates PTK2B/PYK2 in response to T-cell receptor activation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1. Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms'] | 1 | Downloaded from PDB (2DQ7) | 2DQ7 |
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Go to ligands | -18.5600 19.0100 -11.4200 | |
| D0018 | Heat shock protein 90 alpha | P07900 | HS90A_HUMAN | Renal carcinoma antigen NY-REN-38, Lipopolysaccharide-associated protein 2, LPS-associated protein 2, LAP-2, Heat shock protein HSP 90-alpha, Heat shock 86 kDa, HSPCA, HSPC1, HSP90A, HSP86, HSP 86 | Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle. Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues(). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes. Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation. Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. | Other | - | Successful | ['12 Diseases of the respiratory system'] | 1 | ['02 Neoplasms', '08 Diseases of the nervous system'] | 2 | Downloaded from PDB (5J2X) | 5J2X |
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Go to ligands | 2.1300 11.8600 25.8600 | |
| D0019 | Melanin-concentrating hormone receptor 1 | Q99705 | MCHR1_HUMAN | Somatostatinreceptor-like protein, Somatostatin receptor-like protein, SLC1, SLC-1, Melanin-concentrating hormone receptor subtype 1, MCHR-1, MCHR, MCH1R, MCH-R1, MCH-1R, MCH(1) receptor, MCH receptor1, MCH receptor 1, GPR24, G-protein coupled receptor 24, G protein coupled receptor 24 | Receptor for melanin-concentrating hormone, coupled to both G proteins that inhibit adenylyl cyclase and G proteins that activate phosphoinositide hydrolysis. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases'] | 1 | Modelled with SWISS-MODEL (7E32.1.E) | Homology |
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Go to ligands | 101.0300 122.7900 114.8000 | |
| D0020 | S-mephenytoin 4-hydroxylase | P11712 | CP2C9_HUMAN | Cytochrome P450 PB-1, Cytochrome P450 MP-8, Cytochrome P450 MP-4, Cytochrome P450 2C9, Cytochrome P-450MP, Cholesterol 25-hydroxylase, CYPIIC9, CYP2C10, (S)-limonene 7-monooxygenase, (S)-limonene 6-monooxygenase, (R)-limonene 6-monooxygenase | In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan. Cytochromes P450 are a group of heme-thiolate monooxygenases. | Enzyme | Oxidoreductase | Successful | ['01 Certain infectious or parasitic diseases'] | 1 | ['No clinical molecule'] | 0 | Downloaded from PDB (1R9O) | 1R9O |
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Go to ligands | 8.9600 33.4000 -1.7500 | |
| D0021 | Phosphodiesterase 4B | Q07343 | PDE4B_HUMAN | cAMP-specific 3',5'-cyclic phosphodiesterase 4B, Type 4B cAMP phosphodiesterase, Type 4 cyclic adenosine monophosphate phosphodiesterase (type 4 PDE), PDE32, DPDE4 | May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents. Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 6 | Downloaded from PDB (5OHJ) | 5OHJ |
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Go to ligands | -25.4400 -15.3800 28.6200 | |
| D0022 | Tumor necrosis factor | P01375 | TNFA_HUMAN | Tumour necrosis factor alpha, Tumour necrosis factor, Tumor necrosis factor ligand superfamily member 2, TNFalpha, TNFSF2, TNFA, TNF-alpha, TNF-a, TNF alpha, Cachectin | It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective. Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line. Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance. Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. | Factors and Regulators | - | Successful | ['02 Neoplasms', '11 Diseases of the circulatory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 5 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '04 Diseases of the immune system', '05 Endocrine, nutritional or metabolic diseases', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 9 | Downloaded from PDB (7JRA) | 7JRA |
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Go to ligands | -9.8900 -5.3000 -21.3800 | |
| D0023 | Dopamine D3 receptor | P35462 | DRD3_HUMAN | D(3) dopamine receptor | Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation. | Receptor | - | Successful | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system'] | 2 | ['02 Neoplasms', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '17 Conditions related to sexual health'] | 6 | Downloaded from PDB (7CMV) | 7CMV |
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Go to ligands | 95.3300 122.3400 115.4000 | |
| D0024 | Neuropeptide Y receptor type 2 | P49146 | NPY2R_HUMAN | Y2 receptor, NPY2R, NPY2-R, NPY-Y2 receptor | Receptor for neuropeptide Y andpeptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is PYY > NPY > PYY (3-36) > NPY (2-36) > [Ile-31, Gln-34] PP > [Leu- 31, Pro-34] NPY > PP, [Pro-34] PYY and NPY free acid. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases'] | 1 | Downloaded from PDB (7DDZ) | 7DDZ |
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Go to ligands | -23.1700 7.5800 50.0400 | |
| D0025 | Voltage-gated potassium channel Kv11.1 | Q12809 | KCNH2_HUMAN | hERG1, hERG-1, Voltage-gated potassium channel subunit Kv11.1, Potassium voltage-gated channel subfamily H member 2, HERG K+ channel, HERG, H-ERG, Ether-a-go-go-related protein 1, Ether-a-go-go-related gene potassium channel 1, Ether-a-go-go related protein 1, Ether-a-go-go related gene potassium channel 1, Eag related protein 1, Eag homolog, ERG-1, ERG | Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. | Ion Channel | Channels/pores | Successful | ['11 Diseases of the circulatory system'] | 1 | ['01 Certain infectious or parasitic diseases', '07 Sleep-wake disorders', '08 Diseases of the nervous system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 4 | Downloaded from PDB (5VA1) | 5VA1 |
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Go to ligands | 80.5000 71.8000 81.6800 | |
| D0026 | Carbonic anhydrase II | P00918 | CAH2_HUMAN | Carbonic anhydrase C, Carbonic anhydrase 2, Carbonate dehydratase II, CAC | Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6. Essential for bone resorption and osteoclast differentiation. | Enzyme | Lyase | Successful | ['01 Certain infectious or parasitic diseases', '07 Sleep-wake disorders', '09 Diseases of the visual system', '11 Diseases of the circulatory system', '14 Diseases of the skin'] | 5 | ['02 Neoplasms', '15 Diseases of the musculoskeletal system or connective tissue'] | 2 | Downloaded from PDB (3K34) | 3K34 |
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Go to ligands | -7.2400 -1.5900 16.1200 | |
| D0027 | Cyclin-dependent kinase 8 | P49336 | CDK8_HUMAN | Protein kinase K35, Mediator of RNA polymerase II transcription subunit CDK8, Mediator complex subunit CDK8, Cell division protein kinase 8 | Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation. Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5XS2) | 5XS2 |
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Go to ligands | 7.6100 25.5100 -10.9600 | |
| D0028 | Muscarinic acetylcholine receptor M4 | P08173 | ACM4_HUMAN | M4 receptor, CHRM4 | The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase. | Receptor | - | Successful | ['09 Diseases of the visual system', '12 Diseases of the respiratory system', '20 Developmental anomalies', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 4 | ['No clinical molecule'] | 0 | Downloaded from PDB (5DSG) | 5DSG |
|
Go to ligands | 61.6000 0.5600 94.8800 | |
| D0029 | Alpha-galactosidase A | P06280 | AGAL_HUMAN | Melibiase, INN=Agalsidase, Alpha-D-galactoside galactohydrolase, Alpha-D-galactosidase A | A homodimeric glycoprotein that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. Predominantly hydrolyzes ceramide trihexoside, and can catalyze the hydrolysis of melibiose into galactose and glucose. | Enzyme | Hydrolase | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['No clinical molecule'] | 0 | Downloaded from PDB (6IBK) | 6IBK |
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Go to ligands | -24.8400 20.0500 -6.0700 | |
| D0030 | Norepinephrine transporter | P23975 | SC6A2_HUMAN | Solute carrier family 6 member 2, Sodium-dependent noradrenaline transporter, SLC6A2, NET1, NET, NAT1 | Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals. | Transporter | Electrochemical Potential-driven Transporters | Successful | ['02 Neoplasms', '05 Endocrine. Nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '09 Diseases of the visual system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 6 | ['02 Neoplasms', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '13 Diseases of the digestive system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 6 | Modelled with SWISS-MODEL (6VRH.1.A) | Homology |
|
Go to ligands | 134.7000 123.3600 121.9100 | |
| D0031 | Cathepsin K | P43235 | CATK_HUMAN | Cathepsin X, Cathepsin O2, Cathepsin O, CTSO2, CTSO | Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation. Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['15 Diseases of the musculoskeletal system or connective tissue', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 2 | Downloaded from PDB (4X6H) | 4X6H |
|
Go to ligands | 14.4400 4.9300 -16.5900 | |
| D0032 | Toll-like receptor 9 | Q9NR96 | TLR9_HUMAN | UNQ5798/PRO19605, TLR-9, CD289 | Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Controls lymphocyte response to Helicobacter infection. Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '04 Diseases of the immune system', '05 Endocrine, nutritional or metabolic diseases', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '14 Diseases of the skin'] | 7 | Modelled with AlphaFold (AF-Q9NR96-F1-model_v4) | Ab initio |
|
Go to ligands | 10.8700 -4.6400 -32.8400 | |
| D0033 | Dopamine D1 receptor | P21728 | DRD1_HUMAN | D(1A) dopamine receptor | Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase. | Receptor | - | Successful | ['04 Diseases of the immune system', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '18 Pregnancy, childbirth or the puerperium'] | 4 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system'] | 2 | Downloaded from PDB (7JVP) | 7JVP |
|
Go to ligands | 101.0700 84.4700 117.8800 | |
| D0034 | Glutamate receptor ionotropic NMDA 2A | Q12879 | NMDE1_HUMAN | NR2A, NMDA receptor NR2A, N-methyl D-aspartate receptor subtype 2A, HNR2A, Glutamate receptor ionotropic, NMDA 2A, Glutamate [NMDA] receptor subunit epsilon-1, GluN2A | Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition, channels containing GRIN1 and GRIN2A have higher sensitivity to glutamate and faster kinetics than channels formed by GRIN1 and GRIN2B. Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning. Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. | Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['06 Mental, behavioural or neurodevelopmental disorders'] | 1 | Downloaded from PDB (5H8Q) | 5H8Q |
|
Go to ligands | 18.5600 -11.6700 -21.7100 | |
| D0035 | Bacterial DNA gyrase | P20831+P0A0K8 | GYRA_STAAU+GYRB_STAAU | DNA gyrase | DNA gyrase negatively supercoils closed circular double- stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings. | Enzyme | Isomerase | Successful | ['01 Certain infectious or parasitic diseases', '09 Diseases of the visual system', '12 Diseases of the respiratory system', '16 Diseases of the genitourinary system'] | 4 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '09 Diseases of the visual system', '10 Diseases of the ear or mastoid process', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 8 | Downloaded from PDB (6Z1A) | 6Z1A |
|
Go to ligands | 9.3800 40.9500 37.8900 | |
| D0036 | Progesterone receptor | P06401 | PRGR_HUMAN | PR, Nuclear receptor subfamily 3 group C member 3, NR3C3 | Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. | Nuclear Hormone Receptor | - | Successful | ['02 Neoplasms', '16 Diseases of the genitourinary system', '18 Pregnancy, childbirth or the puerperium', '24 Factors influencing health status or contact with health services'] | 4 | ['02 Neoplasms', '16 Diseases of the genitourinary system'] | 2 | Downloaded from PDB (1SQN) | 1SQN |
|
Go to ligands | 11.7500 24.9000 8.0300 | |
| D0037 | Janus kinase 3 | P52333 | JAK3_HUMAN | Tyrosine-protein kinase JAK3, Leukocyte janus kinase, L-JAK | Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion. Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. | Enzyme | Transferase | Successful | ['02 Neoplasms', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 3 | ['02 Neoplasms', '04 Diseases of the immune system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '14 Diseases of the skin'] | 5 | Downloaded from PDB (5LWM) | 5LWM |
|
Go to ligands | 36.1700 22.8000 52.9900 | |
| D0038 | Voltage-gated sodium channel alpha Nav1.7 | Q15858 | SCN9A_HUMAN | hNE-Na, Voltage-gated sodium channel subunit alpha Nav1.7, Sodium channel proteintype IX subunit alpha, Sodium channel proteintype 9 subunit alpha, Sodium channel protein type IX subunit alpha, Sodium channel protein type 9 subunit alpha, Peripheral sodium channel 1, PN1, Neuroendocrine sodium channel, NENA | Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain. Mediates the voltage-dependent sodium ion permeability of excitable membranes. | Ion Channel | Channels/pores | Clinical trial | ['No approved drug'] | 0 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 5 | Downloaded from PDB (7W9K) | 7W9K |
|
Go to ligands | 210.8000 212.4300 194.3700 | |
| D0039 | G1/S-specific cyclin-D1 | P24385 | CCND1_HUMAN | PRAD1 oncogene, PRAD1, Cyclin D1, BCL1, BCL-1 oncogene, BCL-1, B-cell lymphoma 1 protein | Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner. Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. | Factors and Regulators | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6P8E) | 6P8E |
|
Go to ligands | 40.9000 31.5500 50.4200 | |
| D0040 | Valosin-containing protein p97 | P55072 | TERA_HUMAN | Valosin-containing protein, Transitional endoplasmic reticulum ATPase, TER ATPase, 15S Mg(2+)-ATPase p97 subunit | Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A. Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation. Plays a role in the regulation of stress granules (SGs) clearance process upon arsenite-induced response. Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites. Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage. Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation. Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy. Acts as a negative regulator of type I interferon production by interacting with DDX58/RIG-I: interaction takes place when DDX58/RIG-I is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of DDX58/RIG-I. May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation. May more particularly play a role in caveolins sorting in cells. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway. Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (7PUX) | 7PUX |
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Go to ligands | -64.8500 -23.5200 37.4100 | |
| D0041 | Endothelin A receptor | P25101 | EDNRA_HUMAN | HET-AR, Endothelin-1 receptor, Endothelin receptor type A, Endothelin receptor A, ETRA, ETA-R, ETA receptor, ETA, ET-A | Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3. Receptor for endothelin-1. | Receptor | - | Successful | ['11 Diseases of the circulatory system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 2 | ['02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '16 Diseases of the genitourinary system'] | 4 | Downloaded from PDB (8HCQ) | 8HCQ |
|
Go to ligands | 112.1600 111.7300 126.2300 | |
| D0042 | Aryl hydrocarbon receptor | P35869 | AHR_HUMAN | bHLHe76, Class E basic helixloophelix protein 76, Class E basic helix-loop-helix protein 76, AhR, Ah receptor | Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1. The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription. Ligand-activated transcriptional activator. | Receptor | - | Successful | ['03 Diseases of the blood or blood-forming organs', '14 Diseases of the skin'] | 2 | ['02 Neoplasms', '13 Diseases of the digestive system', '14 Diseases of the skin'] | 3 | Downloaded from PDB (7ZUB) | 7ZUB |
|
Go to ligands | 161.1100 164.1500 160.7400 | |
| D0043 | Protein-tyrosine phosphatase SHP-2 | Q06124 | PTN11_HUMAN | Tyrosine-protein phosphatase non-receptor type 11, SHPTP2, SHP2, SHP-2, SH-PTP3, SH-PTP2, Protein-tyrosine phosphatase SHP2, Protein-tyrosine phosphatase 2C, Protein-tyrosine phosphatase 1D, PTP2C, PTP-2C, PTP-1D | Positively regulates MAPK signal transduction pathway. Dephosphorylates GAB1, ARHGAP35 and EGFR. Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulatation of its RhoA binding activity. Dephosphorylates CDC73. Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (7PPM) | 7PPM |
|
Go to ligands | 12.2500 17.1300 -17.1800 | |
| D0044 | B2 bradykinin receptor | P30411 | BKRB2_HUMAN | Bradykinin B2 receptor, BKR2, BK-2 receptor, BK B(2) receptor, B2R | It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. Receptor for bradykinin. | Receptor | - | Successful | ['04 Diseases of the immune system'] | 1 | ['01 Certain infectious or parasitic diseases', '05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system', '22 Injury, poisoning or certain other consequences of external causes'] | 6 | Downloaded from PDB (7F6I) | 7F6I |
|
Go to ligands | 121.0700 130.4100 102.1500 | |
| D0045 | Casein kinase I alpha | P48729 | KC1A_HUMAN | Casein kinase I isoform alpha, CKI-alpha, CK1 | It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'. May phosphorylate PER1 and PER2. May play a role in segregating chromosomes during mitosis. May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6GZD) | 6GZD |
|
Go to ligands | -2.2600 -18.3300 -7.7500 | |
| D0046 | AP endonuclease 1 | P27695 | APEX1_HUMAN | Redox factor-1, REF1, REF-1, HAP1, DNA-(apurinic or apyrimidinic site) lyase, Apurinic-apyrimidinic endonuclease 1, APX, APEX nuclease, APEX, APEN, APE1, APE-1, APE | Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 are DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA. | Enzyme | Lyase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '09 Diseases of the visual system'] | 2 | Downloaded from PDB (7TC2) | 7TC2 |
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Go to ligands | -7.7700 -23.5500 65.8700 | |
| D0047 | Endoplasmic reticulum to nucleus signaling 1 | O75460 | ERN1_HUMAN | Serine/threonine-protein kinase/endoribonuclease IRE1, Ire1-alpha, IRE1a, IRE1, Inositol-requiring protein 1, hIRE1p, Endoplasmic reticulum-to-nucleus signaling 1 | In unstressed cells, the endoplasmic reticulum luminal domain is maintained in its inactive monomeric state by binding to the endoplasmic reticulum chaperone HSPA5/BiP. Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP, allowing the luminal domain to homodimerize, promoting autophosphorylation of the kinase domain and subsequent activation of the endoribonuclease activity. The endoribonuclease activity is specific for XBP1 mRNA and excises 26 nucleotides from XBP1 mRNA. The resulting spliced transcript of XBP1 encodes a transcriptional activator protein that up-regulates expression of UPR target genes. Acts as an upstream signal for ER stress-induced GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane by modulating the expression and localization of SEC16A. Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR). | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6W39) | 6W39 |
|
Go to ligands | 107.0800 42.2000 30.3100 | |
| D0048 | Oxysterols receptor LXR-beta | P55055 | NR1H2_HUMAN | Ubiquitously-expressed nuclear receptor, Nuclear receptor subfamily 1 group H member 2, Nuclear receptor NER, Nuclear orphan receptor LXR-beta, NER, Liver X receptor beta, LXRbeta, LXRB | Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8, DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism. Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex. Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity. | Nuclear Hormone Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['14 Diseases of the skin'] | 1 | Downloaded from PDB (6S5K) | 6S5K |
|
Go to ligands | -8.4900 -12.5900 -15.2100 | |
| D0049 | Dopamine D4 receptor | P21917 | DRD4_HUMAN | DRD4, D(2C)D(4) dopamine receptor dopamine receptor | Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells. | Receptor | - | Successful | ['04 Diseases of the immune system', '06 Mental, behavioural or neurodevelopmental disorders'] | 2 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system'] | 2 | Downloaded from PDB (5WIU) | 5WIU |
|
Go to ligands | -17.2100 14.3100 -16.2800 | |
| D0050 | Tyrosine-protein kinase BTK | Q06187 | BTK_HUMAN | Bruton's tyrosine kinase, Bruton tyrosine kinase, BPK, B-cell progenitor kinase, B cell progenitor kinase, Agammaglobulinemia tyrosine kinase, Agammaglobulinaemia tyrosine kinase, AGMX1 | Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK. BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways. Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway. The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells. Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation. BTK plays also a critical role in transcription regulation. Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes. BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B. Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR. GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression. ARID3A and NFAT are other transcriptional target of BTK. BTK is required for the formation of functional ARID3A DNA-binding complexes. There is however no evidence that BTK itself binds directly to DNA. BTK has a dual role in the regulation of apoptosis. Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '04 Diseases of the immune system', '08 Diseases of the nervous system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 5 | Downloaded from PDB (5P9J) | 5P9J |
|
Go to ligands | 17.4300 7.9500 6.1800 | |
| D0051 | Multidrug resistance protein 1 | P08183 | MDR1_HUMAN | PGY1, P-glycoprotein 1, P-gp, Pgp, MDR1, CD243 antigen, CD243, ATP-binding cassette sub-family B member 1 | Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells. | Transporter | Primary Active Transporters | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms'] | 2 | Downloaded from PDB (7A69) | 7A69 |
|
Go to ligands | 172.1900 92.7100 165.7900 | |
| D0052 | Sterol O-acyltransferase | P35610+O75908 | SOAT1_HUMAN+SOAT2_HUMAN | Cholesterol acyltransferase, Acyl-coenzyme A:cholesterol acyltransferase, ACAT, ACACT | Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol. Plays a role in lipoprotein assembly and dietary cholesterol absorption. In addition to its acyltransferase activity, it may act as a ligase. May provide cholesteryl esters for lipoprotein secretion from hepatocytes and intestinal mucosa. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6L47) | 6L47 |
|
Go to ligands | 122.5100 110.0500 105.6400 | |
| D0053 | NAD-dependent deacetylase sirtuin-1 | Q96EB6 | SIR1_HUMAN | hSIRT1, hSIR2, SIR2L1, SIR2-like protein 1, Regulatory protein SIR2 homolog 1, NAD-dependent protein deacetylase sirtuin-1 | Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively. Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction. Is essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Deacetylates 'Lys-266' of SUV39H1, leading to its activation. Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1. Deacetylates H2A and 'Lys-26' of HIST1H1E. Deacetylates 'Lys-16' of histone H4 (in vitro). Involved in NR0B2/SHP corepression function through chromatin remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression. Proposed to contribute to genomic integrity via positive regulation of telomere length, however, reports on localization to pericentromeric heterochromatin are conflicting. Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1. Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2. This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to accelerate renewal of the heterochromatin which correlates with greater genomic integrity during stress response. Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence. Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I. Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability. Deacetylates FOXO3 in response to oxidative stress thereby increasing its ability to induce cell cycle arrest and resistance to oxidative stress but inhibiting FOXO3-mediated induction of apoptosis transcriptional activity, also leading to FOXO3 ubiquitination and protesomal degradation. Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis. Deacetylates DNMT1, thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing. Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha. Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1. Deacetylates FOXO1 resulting in its nuclear retention and enhancement of its transcriptional activity leading to increased gluconeogenesis in liver. Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation. Involved in HES1- and HEY2-mediated transcriptional repression. In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62'. Deacetylates MEF2D. Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3. Represses HNF1A-mediated transcription. Required for the repression of ESRRG by CREBZF. Deacetylates NR1H3 and NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteosomal degradation and results in cholesterol efflux, a promoter clearing mechanism after reach round of transcription is proposed. Involved in lipid metabolism. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2. Deacetylates p300/EP300 and PRMT1. Deacetylates ACSS2 leading to its activation, and HMGCS1 deacetylation. Involved in liver and muscle metabolism. Through deacteylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletel muscle under low-glucose conditions and is involved in glucose homeostasis. Involved in regulation of PPARA and fatty acid beta-oxidation in liver. Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose, the function seems to imply transcriptional repression of UCP2. Proposed to deacetylate IRS2 thereby facilitating its insulin-induced tyrosine phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression. Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and faciliting recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2. Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN. Transcriptional suppression of XPC probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage. Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1. Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at 'Lys-539' and 'Lys-542' causing it to sequester BAX away from mitochondria thereby inhibiting stress-induced apoptosis. Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8. Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation. Proposed to play role in regulation of STK11/LBK1-dependent AMPK signaling pathways implicated in cellular senescence which seems to involve the regulation of the acetylation status of STK11/LBK1. Can deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic localization and association with STRAD, however, the relevance of such activity in normal cells is unclear. In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation. Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its degradation. Deacetylates CIITA and augments its MHC class II transactivation and contributes to its stability. Deacteylates MECOM/EVI1. Deacetylates PML at 'Lys-487' and this deacetylation promotes PML control of PER2 nuclear localization. During the neurogenic transition, repress selective NOTCH1-target genes through histone deacetylation in a BCL6-dependent manner and leading to neuronal differentiation. Regulates the circadian expression of several core clock genes, including ARNTL/BMAL1, RORC, PER2 and CRY1 and plays a critical role in maintaining a controlled rhythmicity in histone acetylation, thereby contributing to circadian chromatin remodeling. Deacetylates ARNTL/BMAL1 and histones at the circadian gene promoters in order to facilitate repression by inhibitory components of the circadian oscillator. Deacetylates PER2, facilitating its ubiquitination and degradation by the proteosome. Protects cardiomyocytes against palmitate-induced apoptosis. Deacetylates XBP1 isoform 2, deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity. Deacetylates PCK1 and directs its activity toward phosphoenolpyruvate production promoting gluconeogenesis. Involved in the CCAR2-mediated regulation of PCK1 and NR1D1. Deacetylates CTNB1 at 'Lys-49'. In POMC (pro-opiomelanocortin) neurons, required for leptin-induced activation of PI3K signaling. NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metobolism, apoptosis and autophagy. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['04 Diseases of the immune system', '05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '12 Diseases of the respiratory system', '15 Diseases of the musculoskeletal system or connective tissue'] | 5 | Downloaded from PDB (4I5I) | 4I5I |
|
Go to ligands | 42.6000 -20.9200 18.3900 | |
| D0054 | Aldose reductase | P15121 | ALDR_HUMAN | Aldehyde reductase, AKR1B1 | Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies. | Enzyme | Oxidoreductase | Successful | ['08 Diseases of the nervous system', '15 Diseases of the musculoskeletal system or connective tissue'] | 2 | ['05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '09 Diseases of the visual system', '13 Diseases of the digestive system'] | 4 | Downloaded from PDB (4GCA) | 4GCA |
|
Go to ligands | -9.0100 3.1600 2.9700 | |
| D0055 | Induced myeloid leukemia cell differentiation protein Mcl-1 | Q07820 | MCL1_HUMAN | mcl1/EAT, Bcl2-L-3, Bcl-2-related protein EAT/mcl1, Bcl-2-like protein 3, BCL2L3 | Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis. Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. | Factors and Regulators | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6UDV) | 6UDV |
|
Go to ligands | 9.6000 6.5200 96.7400 | |
| D0056 | Focal adhesion kinase 1 | Q05397 | FAK1_HUMAN | pp125FAK, p125FAK, Protein-tyrosine kinase 2, Protein phosphatase 1 regulatory subunit 71, PPP1R71, Focal adhesion kinase-related nonkinase, FRNK, FAK1, FADK 1, FADK | Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation, required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation, this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC, this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1, most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1, GIT2 and SHC1, this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '11 Diseases of the circulatory system'] | 2 | Downloaded from PDB (6YOJ) | 6YOJ |
|
Go to ligands | -13.7300 -3.9600 19.6100 | |
| D0057 | Cationic trypsinogen | P07477 | TRY1_HUMAN | Trypsin-1, Trypsin I, TRYP1, TRY1, TRP1, Serine protease 1, Beta-trypsin | Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec. The single-chain form is more active than the two-chain form against all of these substrates. | Enzyme | Hydrolase | Successful | ['02 Neoplasms'] | 1 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '03 Diseases of the blood or blood-forming organs', '18 Pregnancy, childbirth or the puerperium'] | 4 | Downloaded from PDB (2RA3) | 2RA3 |
|
Go to ligands | 30.6200 -32.7800 20.9300 | |
| D0058 | Cholesteryl ester transfer protein | P11597 | CETP_HUMAN | Lipid transfer protein I, Cholesterol ester transfer protein | Allows the net movement of cholesteryl ester from high density lipoproteins/HDL to triglyceride-rich very low density lipoproteins/VLDL, and the equimolar transport of triglyceride from VLDL to HDL. Regulates the reverse cholesterol transport, by which excess cholesterol is removed from peripheral tissues and returned to the liver for elimination. Involved in the transfer of neutral lipids, including cholesteryl ester and triglyceride, among lipoprotein particles. | Transporter | Channels/pores | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases', '11 Diseases of the circulatory system'] | 2 | Downloaded from PDB (4EWS) | 4EWS |
|
Go to ligands | 9.4300 0.3100 37.3400 | |
| D0059 | Serotonin transporter | P31645 | SC6A4_HUMAN | Solute carrier family 6 member 4, HTT, 5HTT, 5HT transporter | Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner. Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. | Transporter | Electrochemical Potential-driven Transporters | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '09 Diseases of the visual system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 5 | ['06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system', '17 Conditions related to sexual health', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 8 | Downloaded from PDB (5I6X) | 5I6X |
|
Go to ligands | -32.0000 -21.7900 2.3200 | |
| D0060 | Beta-site APP-cleaving enzyme 2 | Q9Y5Z0 | BACE2_HUMAN | Theta-secretase, Membrane-associated aspartic protease 1, Memapsin-1, Down region aspartic protease, DRAP, Beta-site amyloid precursor protein cleaving enzyme 2, Beta-site APP cleaving enzyme 2, Beta-secretase 2, Aspartyl protease 1, Aspartic-like protease 56 kDa, Asp 1, ASP21, ASP1, ALP56, AEPLC | Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. It has also been shown that it can cleave APP between residues 671 and 672. Responsible also for the proteolytic processing of CLTRN in pancreatic beta cells. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['21 Symptoms, signs or clinical findings, not elsewhere classified'] | 1 | Downloaded from PDB (7D5B) | 7D5B |
|
Go to ligands | 22.8600 -7.7000 -15.5200 | |
| D0061 | Tubulin beta-2 chain | Q13885 | TBB2A_HUMAN | Tubulin beta-2A chain, Tubulin beta class IIa, TUBB4B, BetaII-Tubulin, Beta(II)-Tubulin, Beta(II) isotype of Tubulin | It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. Tubulin is the major constituent of microtubules. | Other | - | Successful | ['02 Neoplasms'] | 1 | ['No clinical molecule'] | 0 | Modelled with SWISS-MODEL (6WVL.1.B) | Homology |
|
Go to ligands | -7.0400 98.2800 36.7400 | |
| D0062 | GABA A receptor gamma-3 | Q99928 | GBRG3_HUMAN | GABRG3 | Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functionsas receptor for diazepines and various anesthetics, such as pentobarbital, these are bound at a separate allosteric effector binding site. Functions as ligand- gated chloride channel. | Receptor | - | Successful | ['06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '08 Diseases of the nervous system', '09 Diseases of the visual system', '18 Pregnancy, childbirth or the puerperium', '21 Symptoms, signs or clinical findings, not elsewhere classified', '23 External causes of morbidity or mortality'] | 7 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '20 Developmental anomalies'] | 3 | Modelled with SWISS-MODEL (6HUG.1.C) | Homology |
|
Go to ligands | 136.2000 125.8200 105.4500 | |
| D0063 | Muscarinic acetylcholine receptor M1 | P11229 | ACM1_HUMAN | M1 receptor | Primary transducing effect is Pi turnover. The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. | Receptor | - | Successful | ['08 Diseases of the nervous system', '09 Diseases of the visual system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '16 Diseases of the genitourinary system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 7 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '20 Developmental anomalies', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 6 | Downloaded from PDB (6ZFZ) | 6ZFZ |
|
Go to ligands | 23.2000 19.9000 -5.4100 | |
| D0064 | Signal transducer and activator of transcription 3 | P40763 | STAT3_HUMAN | Acute-phase response factor, APRF | Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): deacetylation and oxidation of lysine residues by LOXL3, leads to disrupt STAT3 dimerization and inhibit its transcription activity. Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1. Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity. Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity). | Factors and Regulators | - | Successful | ['14 Diseases of the skin'] | 1 | ['02 Neoplasms', '04 Diseases of the immune system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system'] | 4 | Downloaded from PDB (6NJS) | 6NJS |
|
Go to ligands | 7.4500 53.6700 1.1300 | |
| D0065 | Pyruvate dehydrogenase kinase 1 | Q15118 | PDK1_HUMAN | Pyruvate dehydrogenase kinase isoform 1, Pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial, PDHK1, PDH kinase 1 | Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases', '12 Diseases of the respiratory system'] | 2 | Downloaded from PDB (2Q8G) | 2Q8G |
|
Go to ligands | -4.2900 39.5900 1.8600 | |
| D0066 | Adrenergic receptor alpha-1B | P35368 | ADA1B_HUMAN | Alpha-1B adrenoreceptor, Alpha-1B adrenoceptor, Alpha-1B adrenergic receptor, Alpha 1B-adrenoreceptor, Alpha 1B-adrenoceptor | Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes. This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. | Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '11 Diseases of the circulatory system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 4 | ['No clinical molecule'] | 0 | Modelled with AlphaFold (AF-P35368-F1-model_v4) | Ab initio |
|
Go to ligands | -8.4600 -0.9300 10.0200 | |
| D0067 | Dipeptidyl peptidase 8 | Q6V1X1 | DPP8_HUMAN | Prolyl dipeptidase DPP8, MSTP141, MSTP135, MSTP097, Dipeptidyl peptidase VIII, Dipeptidyl peptidase IV-related protein 1, DPRP1, DPRP-1, DPP VIII, DP8 | Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '04 Diseases of the immune system'] | 2 | Downloaded from PDB (7OR4) | 7OR4 |
|
Go to ligands | -14.3300 51.2200 37.4300 | |
| D0068 | Acetylcholinesterase | P22303 | ACES_HUMAN | YT, N-ACHE, ARACHE | Role in neuronal apoptosis. Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. | Enzyme | Hydrolase | Successful | ['01 Certain infectious or parasitic diseases', '08 Diseases of the nervous system', '09 Diseases of the visual system', '13 Diseases of the digestive system', '22 Injury, poisoning or certain other consequences of external causes'] | 5 | ['01 Certain infectious or parasitic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 4 | Downloaded from PDB (4M0E) | 4M0E |
|
Go to ligands | 10.3400 -55.1800 -22.6200 | |
| D0069 | Sodium/glucose cotransporter 2 | P31639 | SC5A2_HUMAN | Solute carrier family 5 member 2, Na(+)/glucose cotransporter 2, Low affinity sodium-glucose cotransporter | Has a Na(+) to glucose coupling ratio of 1:1. Sodium-dependent glucose transporter. | Transporter | Electrochemical Potential-driven Transporters | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '11 Diseases of the circulatory system'] | 2 | ['05 Endocrine, nutritional or metabolic diseases', '11 Diseases of the circulatory system', '13 Diseases of the digestive system', '16 Diseases of the genitourinary system'] | 4 | Downloaded from PDB (7VSI) | 7VSI |
|
Go to ligands | 38.1200 50.8900 46.4400 | |
| D0070 | C-C chemokine receptor type 1 | P32246 | CCR1_HUMAN | SCYAR1, RANTES-R, Macrophage inflammatory protein-1 alpha receptor, Macrophage inflammatory protein 1-alpha receptor, MIP-1alpha-R, LD78 receptor, HM145, Chemokine receptor CCR1, CMKR1, CMKBR1, CD191, CCR-1, CC-CKR-1, C-C CKR-1 | Binds to MIP-1-alpha, MIP-1-delta, RANTES, and MCP-3 and, less efficiently, to MIP-1-beta or MCP-1 and subsequently transduces a signal by increasing the intracellular calcium ions level. Responsible for affecting stem cell proliferation. Receptor for a C-C type chemokine. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases', '15 Diseases of the musculoskeletal system or connective tissue'] | 2 | Downloaded from PDB (7VL8) | 7VL8 |
|
Go to ligands | 108.8400 141.0400 128.8100 | |
| D0071 | Trypanosoma Cruzipain | P25779 | CYSP_TRYCR | Cruzaine, Major cysteine proteinase | The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle. | Enzyme | Hydrolase | Successful | ['01 Certain infectious or parasitic diseases'] | 1 | ['No clinical molecule'] | 0 | Downloaded from PDB (1ME3) | 1ME3 |
|
Go to ligands | 3.4600 6.3700 10.4100 | |
| D0072 | Nitric-oxide synthase brain | P29475 | NOS1_HUMAN | Peptidyl-cysteine S-nitrosylase NOS1, Nitric oxide synthase, brain, Neuronal NOS, NOS, type I, NOS type I, NNOS, NC-NOS, N-NOS, BNOS | In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. | Enzyme | Oxidoreductase | Clinical trial | ['No approved drug'] | 0 | ['08 Diseases of the nervous system'] | 1 | Downloaded from PDB (5VV0) | 5VV0 |
|
Go to ligands | 118.9900 246.0000 359.2600 | |
| D0073 | Leukotriene A-4 hydrolase | P09960 | LKHA4_HUMAN | Leukotriene A4 hydrolase, Leukotriene A(4)Leukotriene A-4 hydrolase hydrolase, Leukotriene A(4) hydrolase, LTA4, LTA-H, LTA-4hydrolase, LTA-4 hydrolase | Has also aminopeptidase activity. Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. | Enzyme | Hydrolase | Successful | ['02 Neoplasms'] | 1 | ['13 Diseases of the digestive system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 2 | Downloaded from PDB (3U9W) | 3U9W |
|
Go to ligands | 29.1300 1.7900 2.2700 | |
| D0074 | Histamine H2 receptor | P25021 | HRH2_HUMAN | Histamine receptor 2, HH2R, Gastric receptor I | Appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway. The H2 subclass of histamine receptors mediates gastric acid secretion. | Receptor | - | Successful | ['13 Diseases of the digestive system'] | 1 | ['No clinical molecule'] | 0 | Downloaded from PDB (7UL3) | 7UL3 |
|
Go to ligands | 159.4600 163.9500 199.3400 | |
| D0075 | Rotamase Pin1 | Q13526 | PIN1_HUMAN | Prolyl isomerase Pin1, Peptidyl-prolyl cis-trans isomerase Pin1, Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, Peptidyl prolyl cis/trans isomerase Pin1, PPIase Pin1 | By inducing conformational changes in a subset of phosphorylated proteins, acts as a molecular switch in multiple cellular processes (, Ref. 21). Displays a preference for acidic residues located N-terminally to the proline bond to be isomerized. Regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Down-regulates kinase activity of BTK. Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation. Binds and targets PML and BCL6 for degradation in a phosphorylation-dependent manner. Acts as a regulator of JNK cascade by binding to phosphorylated FBXW7, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation: degradation of FBXW7 leads to subsequent stabilization of JUN. May facilitate the ubiquitination and proteasomal degradation of RBBP8/CtIP through CUL3/KLHL15 E3 ubiquitin-protein ligase complex, hence favors DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR). Peptidyl-prolyl cis/trans isomerase (PPIase) that binds to and isomerizes specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs. | Enzyme | Isomerase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (3I6C) | 3I6C |
|
Go to ligands | -2.4700 19.8200 48.9300 | |
| D0076 | 5-HT 2B receptor | P41595 | 5HT2B_HUMAN | Serotonin receptor 2B, 5-hydroxytryptamine receptor 2B, 5-HT2B, 5-HT-2B, 5-HT 2B | Functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain. Plays a role in the regulation of behavior, including impulsive behavior. Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine. G-protein coupled receptor for 5-hydroxytryptamine (serotonin). | Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders'] | 2 | ['06 Mental, behavioural or neurodevelopmental disorders', '11 Diseases of the circulatory system'] | 2 | Downloaded from PDB (7SRQ) | 7SRQ |
|
Go to ligands | 152.5500 158.1300 155.4200 | |
| D0077 | Protein-tyrosine phosphatase 1B | P18031 | PTN1_HUMAN | Tyrosine-protein phosphatase non-receptor type 1, PTP-1B | Mediates dephosphorylation of EIF2AK3/PERK, inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET. Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases'] | 2 | Downloaded from PDB (7MNA) | 7MNA |
|
Go to ligands | 28.5400 13.9800 1.0700 | |
| D0078 | Apoptosis regulator Bcl-2 | P10415 | BCL2_HUMAN | Bcl-2 | Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release. Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. | Factors and Regulators | - | Successful | ['02 Neoplasms', '08 Diseases of the nervous system'] | 2 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '14 Diseases of the skin'] | 3 | Downloaded from PDB (6GL8) | 6GL8 |
|
Go to ligands | 10.6300 0.8900 13.8200 | |
| D0079 | Dipeptidyl peptidase 4 | P27487 | DPP4_HUMAN | Tcell activation antigen CD26, TP103, T-cell activation antigen CD26, Dipeptidyl peptidase IV, Dipeptidyl peptidase 4 soluble form, DPP-IV, DPP IV, DPP 4, CD26, Adenosine deaminase complexing protein-2, Adenosine deaminase complexing protein 2, ADCP2, ADCP-2, ADABP | Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline. Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. | Enzyme | Hydrolase | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '11 Diseases of the circulatory system', '14 Diseases of the skin'] | 5 | Downloaded from PDB (4A5S) | 4A5S |
|
Go to ligands | 24.8700 64.5200 83.2900 | |
| D0080 | Phospholipase A2 | P04054 | PA21B_HUMAN | Secreted phospholipase A(2), Phosphatidylcholine 2-acylhydrolase 1B, PLA2G1B, Group IB phospholipase A2 | PA2 catalyzes the calcium-dependent hydrolysis of the 2- acyl groups in 3-sn-phosphoglycerides, this releases glycerophospholipids and arachidonic acid that serve as the precursors of signal molecules. | Enzyme | Hydrolase | Successful | ['01 Certain infectious or parasitic diseases', '05 Endocrine. Nutritional or metabolic diseases', '14 Diseases of the skin'] | 3 | ['04 Diseases of the immune system', '05 Endocrine, nutritional or metabolic diseases', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 6 | Downloaded from PDB (3ELO) | 3ELO |
|
Go to ligands | -12.9500 -26.3400 -3.7500 | |
| D0081 | 5-HT 6 receptor | P50406 | 5HT6R_HUMAN | Serotonin receptor 6, 5-hydroxytryptamine receptor 6, 5-HT6 receptor, 5-HT6, 5-HT-6 | The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs. Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity. Is an activator of TOR signaling. This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system'] | 3 | Downloaded from PDB (7YS6) | 7YS6 |
|
Go to ligands | 115.8000 176.4100 138.8100 | |
| D0082 | Lysine-specific histone demethylase 1 | O60341 | KDM1A_HUMAN | Lysine-specific histone demethylase 1A, LSD1, KIAA0601, KDM1, Flavin-containing amine oxidase domain-containing protein 2, BRAF35-HDAC complex protein BHC110, AOF2 | Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. Also acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in ANDR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Effector of SNAI1-mediated transcription repression of E-cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7. | Enzyme | Oxidoreductase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '08 Diseases of the nervous system'] | 2 | Downloaded from PDB (2Z3Y) | 2Z3Y |
|
Go to ligands | 26.7000 43.5000 36.0400 | |
| D0083 | X-linked inhibitor of apoptosis protein | P98170 | XIAP_HUMAN | hILP, hIAP3, hIAP-3, Xlinked IAP, X-linked IAP, RING-type E3 ubiquitin transferase XIAP, Inhibitor of apoptosis protein 3, ILP, IAPlike protein, IAP3, IAP-like protein, IAP-3, E3 ubiquitinprotein ligase XIAP, E3 ubiquitin-protein ligase XIAP, Baculoviral IAP repeatcontaining protein 4, Baculoviral IAP repeat-containing protein 4, BIRC4, API3 | Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors (NLRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program. Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases'] | 2 | Downloaded from PDB (4KJU) | 4KJU |
|
Go to ligands | 22.8700 36.4500 12.2600 | |
| D0084 | Protein arginine methyltransferase 1 | Q99873 | ANM1_HUMAN | Protein arginine N-methyltransferase 1, Interferon receptor 1-bound protein 4, IR1B4, Histone-arginine N-methyltransferase PRMT1, HRMT1L2, HMT2 | Constitutes the main enzyme that mediates monomethylation and asymmetric dimethylation of histone H4 'Arg-4' (H4R3me1 and H4R3me2a, respectively), a specific tag for epigenetic transcriptional activation. May be involved in the regulation of TAF15 transcriptional activity, act as an activator of estrogen receptor (ER)-mediated transactivation, play a key role in neurite outgrowth and act as a negative regulator of megakaryocytic differentiation, by modulating p38 MAPK pathway. Methylates RBM15, promoting ubiquitination and degradation of RBM15. Methylates FOXO1 and retains it in the nucleus increasing its transcriptional activity. Methylates CHTOP and this methylation is critical for its 5-hydroxymethylcytosine (5hmC)-binding activity. Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner. Arginine methyltransferase that methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues present in proteins such as ESR1, histone H2, H3 and H4, ILF3, HNRNPA1, HNRNPD, NFATC2IP, SUPT5H, TAF15, EWS, HABP4 and SERBP1. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6NT2) | 6NT2 |
|
Go to ligands | -7.4900 51.3200 -28.9400 | |
| D0085 | Carbonic anhydrase XIV | Q9ULX7 | CAH14_HUMAN | UNQ690/PRO1335, Carbonic anhydrase 14, Carbonate dehydratase XIV | Reversible hydration of carbon dioxide. | Enzyme | Lyase | Successful | ['01 Certain infectious or parasitic diseases', '05 Endocrine. Nutritional or metabolic diseases'] | 2 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5CJF) | 5CJF |
|
Go to ligands | 67.8500 37.2400 3.0000 | |
| D0086 | 5-HT 2A receptor | P28223 | 5HT2A_HUMAN | Serotonin receptor 2A, HTR2, 5-hydroxytryptamine receptor 2A, 5-HT-2A, 5-HT-2 | G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction. | Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system'] | 3 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '08 Diseases of the nervous system', '09 Diseases of the visual system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '16 Diseases of the genitourinary system', '17 Conditions related to sexual health', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 11 | Downloaded from PDB (7WC8) | 7WC8 |
|
Go to ligands | -28.8100 -12.2800 143.2100 | |
| D0087 | DNA topoisomerase II alpha | P11388 | TOP2A_HUMAN | DNA topoisomerase II, alpha isozyme, DNA topoisomerase 2alpha, DNA topoisomerase 2-alpha | Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation. Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. | Enzyme | Isomerase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5GWK) | 5GWK |
|
Go to ligands | 32.2500 -21.9800 -55.3100 | |
| D0088 | Menin-MLL1 interaction | O00255+Q03164 | MEN1_HUMAN-KMT2A_HUMAN | Unavailable | Unavailable | Factors and Regulators | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4GQ4) | 4GQ4 |
|
Go to ligands | -11.7600 9.8000 13.9400 | |
| D0089 | Steryl-sulfatase | P08842 | STS_HUMAN | Steryl-sulfate sulfohydrolase, Steroid sulfatase, STS, Estrone sulfatase, Arylsulfatase C, ASC | Conversion of sulfated steroid precursors to estrogens during pregnancy. | Enzyme | Hydrolase | Successful | ['04 Diseases of the immune system'] | 1 | ['02 Neoplasms', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system'] | 3 | Downloaded from PDB (8EG3) | 8EG3 |
|
Go to ligands | 73.6000 -1.2200 24.2100 | |
| D0090 | Vitamin D3 receptor | P11473 | VDR_HUMAN | Vitamin D(3) receptor, Nuclear vitamin D receptor, Nuclear receptor subfamily 1 group I member 1, NR1I1, 1,25-dihydroxyvitamin D3 receptor | Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR. The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes. Plays a central role in calcium homeostasis. Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells. | Nuclear Hormone Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '14 Diseases of the skin', '16 Diseases of the genitourinary system', '20 Developmental anomalies'] | 4 | ['02 Neoplasms', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system'] | 3 | Downloaded from PDB (3B0T) | 3B0T |
|
Go to ligands | -10.7100 -3.2900 31.9400 | |
| D0091 | Neuronal acetylcholine receptor alpha-7 | P36544 | ACHA7_HUMAN | Nicotinic acetylcholine receptor subunit alpha 7, Nicotinic acetylcholine receptor alpha7, CHRNA7, Alpha7 nicotinic receptor, Alpha7 nAChR, Alpha-7 nAChR, Alpha(7) nicotinic receptor | After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is blocked by alpha-bungarotoxin. | Receptor | - | Successful | ['06 Mental, behavioural or neurodevelopmental disorders', '09 Diseases of the visual system'] | 2 | ['02 Neoplasms', '04 Diseases of the immune system', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '12 Diseases of the respiratory system', '20 Developmental anomalies'] | 6 | Downloaded from PDB (5AFN) | 5AFN |
|
Go to ligands | 26.4600 7.2600 41.8600 | |
| D0092 | Monoglyceride lipase | Q99685 | MGLL_HUMAN | Monoacylglycerol lipase, MGL, Lysophospholipaselike, Lysophospholipase-like, Lysophospholipase homolog, HUK5, HU-K5 | Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain. Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth. Converts monoacylglycerides to free fatty acids and glycerol. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['08 Diseases of the nervous system'] | 1 | Downloaded from PDB (3PE6) | 3PE6 |
|
Go to ligands | -12.1400 19.9600 -7.6000 | |
| D0093 | Prostaglandin E2 receptor EP4 | P35408 | PE2R4_HUMAN | Prostanoid EP4 receptor, Prostaglandin E2 receptor EP4 subtype, PTGER2, PGE2 receptor EP4 subtype, PGE receptor EP4 subtype | Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '21 Symptoms, signs or clinical findings, not elsewhere classified', '24 Factors influencing health status or contact with health services'] | 6 | Downloaded from PDB (5YWY) | 5YWY |
|
Go to ligands | -45.9600 -42.0500 2.1400 | |
| D0094 | Group IIA phospholipase A2 | P14555 | PA2GA_HUMAN | RASF-A, Phospholipase A2, membrane associated, Phosphatidylcholine 2-acylhydrolase 2A, PLA2L, PLA2B, Non-pancreatic secretory phospholipase A2, NPS-PLA2, GIIC sPLA2 | Catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Thought to participate in the regulation of phospholipid metabolism in biomembranes including eicosanoid biosynthesis. Independent of its catalytic activity, acts as a ligand for integrins. Binds to and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1. Binds to a site (site 2) which is distinct from the classical ligand-binding site (site 1) and induces integrin conformational changes and enhanced ligand binding to site 1. Induces cell proliferation in an integrin-dependent manner. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5G3N) | 5G3N |
|
Go to ligands | -5.1100 38.4000 -2.7500 | |
| D0095 | Integrin alpha-L | P20701 | ITAL_HUMAN | Lymphocyte Function-associated Antigen-1, Leukocyte function-associated molecule 1 alpha chain, Leukocyte function associated molecule 1, alpha chain, Leukocyte adhesion glycoprotein LFA-1 alpha chain, LFA-1A, LFA-1, CD11a, CD11 antigen-like family member A | Integrin ITGAL/ITGB2 is a receptor for F11R. Integin ITGAL/ITGB2 is a receptor for the secreted form of ubiquitin-like protein ISG15, the interaction is mediated by ITGAL. Involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes. Contributes to natural killer cell cytotoxicity. Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils. Required for generation of common lymphoid progenitor cells in bone marrow, indicating a role in lymphopoiesis. Integrin ITGAL/ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages. Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. | Receptor | - | Successful | ['09 Diseases of the visual system', '14 Diseases of the skin'] | 2 | ['09 Diseases of the visual system', '22 Injury, poisoning or certain other consequences of external causes'] | 2 | Downloaded from PDB (2ICA) | 2ICA |
|
Go to ligands | -6.3900 0.5300 26.5500 | |
| D0096 | Melanocortin receptor 1 | Q01726 | MSHR_HUMAN | Melanotropin receptor, Melanocyte-stimulating hormone receptor, Melanocortin-1 receptor, MSHR, MSH-R, MC1-R | The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Receptor for MSH (alpha, beta and gamma) and ACTH. | Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '17 Conditions related to sexual health'] | 2 | ['05 Endocrine, nutritional or metabolic diseases', '13 Diseases of the digestive system', '14 Diseases of the skin', '17 Conditions related to sexual health'] | 4 | Downloaded from PDB (7F4H) | 7F4H |
|
Go to ligands | 136.9600 106.1200 99.7400 | |
| D0097 | Proteinase activated receptor 1 | P25116 | PAR1_HUMAN | Thrombin receptor, Proteinase-activated receptor 1, Protease-activated receptor-1, Protease activated receptor 1, PAR1, PAR-1, Coagulation factor II receptor, CF2R | May play a role in platelets activation and in vascular development. High affinity receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis. | Receptor | - | Successful | ['11 Diseases of the circulatory system'] | 1 | ['11 Diseases of the circulatory system'] | 1 | Downloaded from PDB (3VW7) | 3VW7 |
|
Go to ligands | -4.0600 -9.7900 57.6900 | |
| D0098 | Cannabinoid receptor 2 | P34972 | CNR2_HUMAN | hCB2, Cannabinoid CB2 receptor, CX5, CB2B, CB2A, CB-2 | May function in inflammatory response, nociceptive transmission and bone homeostasis. Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. | Receptor | - | Successful | ['06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders'] | 2 | ['05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '09 Diseases of the visual system', '13 Diseases of the digestive system', '14 Diseases of the skin', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 6 | Downloaded from PDB (6KPC) | 6KPC |
|
Go to ligands | 10.4800 0.9900 -45.5500 | |
| D0099 | Phosphoinositide dependent protein kinase-1 | O15530 | PDPK1_HUMAN | PDK1, HPDK1, 3-phosphoinositide-dependent protein kinase 1, 3-Phosphoinositide-dependent kinase-1, 3'-phosphoinositide dependent kinase 1 | Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive. Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5LVO) | 5LVO |
|
Go to ligands | -13.0500 33.9900 -12.0500 | |
| D0100 | Hypoxia-inducible factor 2 alpha | Q99814 | EPAS1_HUMAN | bHLHe73, PASD2, PAS domain-containing protein 2, Member of PAS protein 2, MOP2, Hypoxia-inducible factor 2-alpha, HLF, HIF2A, HIF2-alpha, HIF-2-alpha, HIF-1-alpha-like factor, Endothelial PAS domain-containing protein 1, EPAS-1, Class E basic helix-loop-helix protein 73, Basic-helix-loop-helix-PAS protein MOP2 | Heterodimerizes with ARNT, heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation requires recruitment of transcriptional coactivators such as CREBBP and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD. Transcription factor involved in the induction of oxygen regulated genes. | Factors and Regulators | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4GHI) | 4GHI |
|
Go to ligands | 14.5200 -42.5200 10.1300 | |
| D0101 | MAPK-activated protein kinase 2 | P49137 | MAPK2_HUMAN | MK2, MK-2, MAPKactivated protein kinase 2, MAPKAPK-2, MAPKAP-K2, MAPKAP kinase 2, MAP kinaseactivated protein kinase 2, MAP kinase-activated protein kinase 2 | Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1, leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '12 Diseases of the respiratory system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 4 | Downloaded from PDB (3M2W) | 3M2W |
|
Go to ligands | 40.1000 7.4700 17.1900 | |
| D0102 | Voltage-gated calcium channel alpha Cav2.2 | Q00975 | CAC1B_HUMAN | Voltage-gated calcium channel alpha subunit Cav2.2, Voltage-dependent N-type calcium channel alpha-1B subunit, N-type Ca2+ channel, Calcium channel, L type, alpha-1 polypeptide isoform 5, CACNA1B, Brain calcium channel III, BIII | Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin- IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons. | Ion Channel | Channels/pores | Successful | ['03 Diseases of the blood or blood-forming organs', '08 Diseases of the nervous system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 3 | ['08 Diseases of the nervous system', '11 Diseases of the circulatory system', '22 Injury, poisoning or certain other consequences of external causes'] | 3 | Downloaded from PDB (7VFU) | 7VFU |
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Go to ligands | 173.3300 180.5400 189.0900 | |
| D0103 | Prostaglandin E2 receptor EP2 | P43116 | PE2R2_HUMAN | Prostanoid EP2 receptor, Prostaglandin E2 receptor EP2 subtype, PGE2 receptor EP2 subtype, PGE receptor, EP2 subtype, PGE receptor EP2 subtype, EP2 receptor | The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the relaxing effect of this receptor on smooth muscle. Receptor for prostaglandin E2 (PGE2). | Receptor | - | Successful | ['09 Diseases of the visual system', '11 Diseases of the circulatory system', '17 Conditions related to sexual health', '18 Pregnancy, childbirth or the puerperium', '22 Injury, poisoning or certain other consequences of external causes'] | 5 | ['02 Neoplasms', '11 Diseases of the circulatory system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system', '24 Factors influencing health status or contact with health services'] | 6 | Downloaded from PDB (7CX2) | 7CX2 |
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Go to ligands | 86.0400 114.3100 118.2900 | |
| D0104 | Voltage-gated sodium channel alpha Nav1.5 | Q14524 | SCN5A_HUMAN | Voltage-gated sodium channel subunit alpha Nav1.5, Sodium channel protein type V subunit alpha, Sodium channel protein type 5 subunit alpha, Sodium channel protein cardiac muscle subunit alpha, HH1 | Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels. This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. | Ion Channel | Channels/pores | Successful | ['01 Certain infectious or parasitic diseases', '08 Diseases of the nervous system', '09 Diseases of the visual system', '11 Diseases of the circulatory system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 5 | ['11 Diseases of the circulatory system'] | 1 | Downloaded from PDB (6LQA) | 6LQA |
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Go to ligands | 128.5600 125.2300 137.6600 | |
| D0105 | Glucocorticoid receptor | P04150 | GCR_HUMAN | Nuclear receptor subfamily 3 group C member 1, GRL, GR | Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling. Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity). | Nuclear Hormone Receptor | - | Successful | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '04 Diseases of the immune system', '05 Endocrine. Nutritional or metabolic diseases', '08 Diseases of the nervous system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '15 Diseases of the musculoskeletal system or connective tissue'] | 8 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '09 Diseases of the visual system', '10 Diseases of the ear or mastoid process', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 9 | Downloaded from PDB (4UDD) | 4UDD |
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Go to ligands | 36.3600 20.9100 11.4000 | |
| D0106 | Proto-oncogene c-Met | P08581 | MET_HUMAN | Tyrosine-protein kinase Met, Scatter factor receptor, SF receptor, Met proto-oncogene tyrosine kinase, Hepatocyte growth factor receptor, HGF/SF receptor, HGF-SF receptor, HGF receptor, C-met, C-Met receptor tyrosine kinase | Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis. Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '13 Diseases of the digestive system', '16 Diseases of the genitourinary system', '22 Injury, poisoning or certain other consequences of external causes'] | 6 | Downloaded from PDB (3DKC) | 3DKC |
|
Go to ligands | 17.9100 29.0200 21.0500 | |
| D0107 | Histone deacetylase 6 | Q9UBN7 | HDAC6_HUMAN | KIAA0901, JM21, HD6 | Gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Plays a central role in microtubule-dependent cell motility via deacetylation of tubulin. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5WPB) | 5WPB |
|
Go to ligands | 4.0500 0.5900 9.5600 | |
| D0108 | Gastrin/cholecystokinin type B receptor | P32239 | GASR_HUMAN | Cholecystokinin-2 receptor, CCKRB, CCK2-R, CCK-BR, CCK-B receptor | The CCK-B receptors occur throughout the central nervous system where they modulate anxiety, analgesia, arousal, and neuroleptic activity. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Receptor for gastrin and cholecystokinin. | Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '13 Diseases of the digestive system'] | 4 | Downloaded from PDB (7F8W) | 7F8W |
|
Go to ligands | 115.8800 119.8300 141.2100 | |
| D0109 | Xanthine dehydrogenase/oxidase | P47989 | XDH_HUMAN | Xanthine oxidase, Xanthine dehydrogenase, XDHA | Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro). Key enzyme in purine degradation. | Enzyme | Oxidoreductase | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system'] | 6 | Downloaded from PDB (2CKJ) | 2CKJ |
|
Go to ligands | 75.0800 72.8500 147.6200 | |
| D0110 | Adrenergic receptor alpha-2B | P18089 | ADA2B_HUMAN | Subtype C2, Alpha-2BAR, Alpha-2B adrenoreceptor, Alpha-2B adrenoceptor, Alpha-2B adrenergic receptor, Alpha-2 adrenergic receptor subtype C2, ADRA2RL1, ADRA2L1 | The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol. Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. | Receptor | - | Successful | ['06 Mental, behavioural or neurodevelopmental disorders'] | 1 | ['08 Diseases of the nervous system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 2 | Downloaded from PDB (6K41) | 6K41 |
|
Go to ligands | 108.9400 105.5400 141.1300 | |
| D0111 | Glutamate receptor AMPA 2 | P42262 | GRIA2_HUMAN | Glutamate receptor ionotropic, AMPA 2, Glutamate receptor 2, GluRK2, GluRB, GluR2, GluR-K2, GluR-B, GluR-2, GluA2, AMPAselective glutamate receptor 2, AMPA-selective glutamate receptor 2 | L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate. Through complex formation with NSG1, GRIP1 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting. Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. | Receptor | - | Successful | ['08 Diseases of the nervous system'] | 1 | ['08 Diseases of the nervous system'] | 1 | Downloaded from PDB (5ZG2) | 5ZG2 |
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Go to ligands | -8.7400 -28.8100 -21.4900 | |
| D0112 | Coagulation factor VII | P08709 | FA7_HUMAN | Serum prothrombin conversion accelerator, SPCA, Proconvertin, Eptacog alfa | Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calcium. | Enzyme | Hydrolase | Successful | ['03 Diseases of the blood or blood-forming organs'] | 1 | ['03 Diseases of the blood or blood-forming organs', '16 Diseases of the genitourinary system'] | 2 | Downloaded from PDB (5PAG) | 5PAG |
|
Go to ligands | 9.2500 35.1300 23.8500 | |
| D0113 | Voltage-gated sodium channel alpha Nav1.8 | Q9Y5Y9 | SCNAA_HUMAN | hPN3, Voltage-gated sodium channel subunit alpha Nav1.8, Sodium channel protein type X subunit alpha, Sodium channel protein type 10 subunit alpha, Peripheral nerve sodium channel 3, PN3 | Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms. | Ion Channel | Channels/pores | Successful | ['01 Certain infectious or parasitic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '09 Diseases of the visual system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 4 | ['02 Neoplasms', '08 Diseases of the nervous system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 3 | Downloaded from PDB (7WE4) | 7WE4 |
|
Go to ligands | 138.0300 137.0500 129.3900 | |
| D0114 | Adrenergic receptor beta-1 | P08588 | ADRB1_HUMAN | Beta-1 adrenoreceptor, Beta-1 adrenoceptor, Beta-1 adrenergic receptor, B1AR, ADRB1R | Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling. | Receptor | - | Successful | ['01 Certain infectious or parasitic diseases', '04 Diseases of the immune system', '08 Diseases of the nervous system', '09 Diseases of the visual system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system'] | 6 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '11 Diseases of the circulatory system'] | 3 | Downloaded from PDB (7BVQ) | 7BVQ |
|
Go to ligands | 21.5800 -22.6200 2.9600 | |
| D0115 | Tissue-type plasminogen activator | P00750 | TPA_HUMAN | TPA, T-plasminogen activator, T-PA, Reteplase, Alteplase | By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. Plays a direct role in facilitating neuronal migration. Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. | Enzyme | Hydrolase | Successful | ['16 Diseases of the genitourinary system', '22 Injury, poisoning or certain other consequences of external causes'] | 2 | ['No clinical molecule'] | 0 | Downloaded from PDB (1BDA) | 1BDA |
|
Go to ligands | 9.1300 51.3000 28.3500 | |
| D0116 | Proto-oncogene c-RAF | P04049 | RAF1_HUMAN | cRaf, Raf-1, RAF proto-oncogene serine/threonine-protein kinase, RAF | RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '13 Diseases of the digestive system'] | 3 | Downloaded from PDB (3OMV) | 3OMV |
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Go to ligands | 6.3600 20.7100 33.8200 | |
| D0117 | Muscarinic acetylcholine receptor M2 | P08172 | ACM2_HUMAN | M2 receptor, CHRM2 | The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3), this then triggers calcium ion release into the cytosol. | Receptor | - | Successful | ['09 Diseases of the visual system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 5 | ['21 Symptoms, signs or clinical findings, not elsewhere classified'] | 1 | Downloaded from PDB (3UON) | 3UON |
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Go to ligands | 7.8600 0.8800 -3.8600 | |
| D0118 | Opioid receptor sigma 1 | Q99720 | SGMR1_HUMAN | hSigmaR1, Sigma1R, Sigma1-receptor, Sigma non-opioid intracellular receptor 1, Sigma 1-type opioid receptor, SRBP, SR31747-binding protein, SR31747 binding protein 1, SR-BP, SIG-1R, Opioid receptor, sigma 1, isoform 1, OPRS1 protein, Aging-associated gene 8 protein, AAG8 | Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration. Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria. Plays a role in protecting cells against oxidative stress-induced cell death via its interaction with RNF112. Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. | Receptor | - | Successful | ['21 Symptoms, signs or clinical findings, not elsewhere classified'] | 1 | ['04 Diseases of the immune system', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '12 Diseases of the respiratory system', '17 Conditions related to sexual health', '20 Developmental anomalies', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 7 | Downloaded from PDB (5HK1) | 5HK1 |
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Go to ligands | -10.3800 20.2600 -24.3800 | |
| D0119 | Poly [ADP-ribose] polymerase 1 | P09874 | PARP1_HUMAN | Protein poly-ADP-ribosyltransferase PARP1, Poly[ADP-ribose] synthetase-1, Poly[ADP-ribose] synthase 1, Poly(ADP-ribose)polymerase-1, PPOL, PARP-1, NAD(+)Poly [ADP-ribose] polymerase-1 ADP-ribosyltransferase-1, NAD(+) ADP-ribosyltransferase-1, NAD(+) ADP-ribosyltransferase 1, DNA ADP-ribosyltransferase PARP1, ARTD1, ADPRT 1, ADPRT, ADP-ribosyltransferase diphtheria toxin-like 1 | Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of glutamate and aspartate residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units. Mediates the poly(ADP-ribosyl)ation of a number of proteins, including itself, APLF and CHFR. Also mediates serine ADP-ribosylation of target proteins following interaction with HPF1, HPF1 conferring serine specificity. Probably also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1. Catalyzes the poly-ADP-ribosylation of histones in a HPF1-dependent manner. Involved in the base excision repair (BER) pathway by catalyzing the poly-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation. In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. Acts as a regulator of transcription: positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming. Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair. | Enzyme | Transferase | Successful | ['02 Neoplasms', '14 Diseases of the skin'] | 2 | ['02 Neoplasms', '08 Diseases of the nervous system'] | 2 | Downloaded from PDB (7KK5) | 7KK5 |
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Go to ligands | -89.2400 -1.2100 3.2400 | |
| D0120 | Toll-like receptor 7 | Q9NYK1 | TLR7_HUMAN | Toll-like receptor 7 | Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR7 is a nucleotide-sensing TLR which is activated by single-stranded RNA. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (By similarity). | Receptor | - | Successful | ['01 Certain infectious or parasitic diseases', '02 Neoplasms'] | 2 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '04 Diseases of the immune system', '05 Endocrine, nutritional or metabolic diseases', '12 Diseases of the respiratory system', '14 Diseases of the skin'] | 6 | Downloaded from PDB (7CYN) | 7CYN |
|
Go to ligands | 130.8600 114.3800 57.3300 | |
| D0121 | Protein kinase C theta | Q04759 | KPCT_HUMAN | Protein kinase C theta type, PRKCT, NPKC-theta | In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1. Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['22 Injury, poisoning or certain other consequences of external causes'] | 1 | Downloaded from PDB (5F9E) | 5F9E |
|
Go to ligands | 24.9200 75.9500 -7.8600 | |
| D0122 | P2Y purinoceptor 12 | Q9H244 | P2Y12_HUMAN | SP1999, P2Y12 platelet ADP receptor, P2Y12, P2Y(cyc), P2Y(ADP)P2Y purinoceptor 12, P2Y(ADP), P2Y(AC), P2T(AC), P2RY12, Nucleotide P2Y(12) receptor, Adenosine P2Y12 receptor, ADPG-R, ADP-glucose receptor | Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation. | Receptor | - | Successful | ['11 Diseases of the circulatory system', '13 Diseases of the digestive system'] | 2 | ['11 Diseases of the circulatory system', '13 Diseases of the digestive system'] | 2 | Downloaded from PDB (4TNJ) | 4TNJ |
|
Go to ligands | 13.2700 -2.4500 52.4900 | |
| D0123 | Rotamase A | P62937 | PPIA_HUMAN | PPIA, Cyclophilin A, CyPA | Ppiases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. | Enzyme | Isomerase | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['No clinical molecule'] | 0 | Downloaded from PDB (4N1M) | 4N1M |
|
Go to ligands | -0.9600 10.6600 -6.7200 | |
| D0124 | Voltage-gated calcium channel alpha Cav1.3 | Q01668 | CAC1D_HUMAN | Voltage-gated calcium channel alpha subunit Cav1.3, Voltage-gated L-type Ca2+ channel alpha1D, Calcium channel, L type, alpha-1 polypeptide, isoform 2, CACNA1D | Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). | Ion Channel | Channels/pores | Clinical trial | ['No approved drug'] | 0 | ['08 Diseases of the nervous system'] | 1 | Downloaded from PDB (8E59) | 8E59 |
|
Go to ligands | 150.7900 165.0600 150.2000 | |
| D0125 | Fibroblast growth factor receptor 1 | P11362 | FGFR1_HUMAN | c-fgr, bFGF-R-1, bFGF-R, N-sam, HBGFR, Fms-like tyrosine kinase 2, FLT2, FLT-2, FLG, FGFR-1, FGFBR, CEK, CD331 antigen, CD331, Basic fibroblast growth factor receptor 1, BFGFR | Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation. Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. | Enzyme | Transferase | Successful | ['02 Neoplasms', '03 Diseases of the blood or blood-forming organs', '12 Diseases of the respiratory system'] | 3 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '13 Diseases of the digestive system', '14 Diseases of the skin'] | 6 | Downloaded from PDB (5EW8) | 5EW8 |
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Go to ligands | 87.9300 0.5600 14.7400 | |
| D0126 | Ileal sodium/bile acid cotransporter | Q12908 | NTCP2_HUMAN | Solute carrier family 10 member 2, Sodium/taurocholate cotransporting polypeptide, ileal, SLC10A2, Na(+)dependent ileal bile acid transporter, Ileal sodiumdependent bile acid transporter, Ileal Na(+)/bile acid cotransporter, ISBT, IBAT, Apical sodiumdependent bile acid transporter, ASBT | Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Plays a key role in cholesterol metabolism. | Transporter | Electrochemical Potential-driven Transporters | Successful | ['14 Diseases of the skin'] | 1 | ['05 Endocrine, nutritional or metabolic diseases', '13 Diseases of the digestive system', '20 Developmental anomalies'] | 3 | Modelled with SWISS-MODEL (7PQG.1.B) | Homology |
|
Go to ligands | 153.5100 160.7300 165.9000 | |
| D0127 | Nuclear receptor ROR-gamma | P51449 | RORG_HUMAN | Retinoid-related orphan receptor-gamma, RZRG, RORG, RAR-related orphan receptor C, Nuclear receptor subfamily 1 group F member 3, Nuclear receptor RZR-gamma, NR1F3 | Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates the circadian expression of clock genes such as CRY1, ARNTL/BMAL1 and NR1D1 in peripheral tissues and in a tissue-selective manner. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORC-mediated activation of the expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Involved in the regulation of the rhythmic expression of genes involved in glucose and lipid metabolism, including PLIN2 and AVPR1A. Negative regulator of adipocyte differentiation through the regulation of early phase genes expression, such as MMP3. Controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. In liver, has specific and redundant functions with RORA as positive or negative modulator of expression of genes encoding phase I and Phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as SULT1E1. Also plays also a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC and PCK1. Regulates the rhythmic expression of PROX1 and promotes its nuclear localization. Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity. | Nuclear Hormone Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '04 Diseases of the immune system', '08 Diseases of the nervous system', '13 Diseases of the digestive system', '14 Diseases of the skin'] | 5 | Downloaded from PDB (6W9I) | 6W9I |
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Go to ligands | -8.8400 24.5300 15.1200 | |
| D0128 | Free fatty acid receptor 1 | O14842 | FFAR1_HUMAN | Gprotein coupled receptor 40, FFAR1 | G-protein coupled receptor for medium and long chain saturated and unsaturated fatty acids that plays an important role in glucose homeostasis. Fatty acid binding increases glucose- stimulated insulin secretion, and may also enhance the secretion of glucagon-like peptide 1 (GLP-1). May also play a role in bone homeostasis, receptor signaling activates pathways that inhibit osteoclast differentiation. Ligand binding leads to a conformation change that triggers signaling via G-proteins that activate phospholipase C, leading to an increase of the intracellular calcium concentration. Seems to act through a G(q) and G(i)-mediated pathway. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases', '12 Diseases of the respiratory system'] | 2 | Downloaded from PDB (5TZR) | 5TZR |
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Go to ligands | -43.8500 -2.6000 60.0600 | |
| D0129 | Opioid receptor mu | P35372 | OPRM_HUMAN | hMOP, Mu-type opioid receptor, Mu opioid receptor, Mu opiate receptor, MOR1A, MOR1, MOR-1, M-OR-1 | Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity. Receptor for endogenous opioids such as beta-endorphin and endomorphin. | Receptor | - | Successful | ['06 Mental, behavioural or neurodevelopmental disorders', '09 Diseases of the visual system', '13 Diseases of the digestive system', '14 Diseases of the skin', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 5 | ['05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 5 | Downloaded from PDB (8EFO) | 8EFO |
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Go to ligands | 185.2600 171.4300 172.0500 | |
| D0130 | Insulin-like growth factor I receptor | P08069 | IGF1R_HUMAN | Type 1 insulin-like growth factor receptor, Insulin-like growth factor 1 receptor, IGF-IR, IGF-I receptor, IGF-1R, IGF-1 receptor, CD221 antigen, CD221 | Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R. Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). | Enzyme | Transferase | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '20 Developmental anomalies'] | 2 | ['02 Neoplasms', '08 Diseases of the nervous system', '09 Diseases of the visual system', '16 Diseases of the genitourinary system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 5 | Downloaded from PDB (3LW0) | 3LW0 |
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Go to ligands | -4.7200 -57.2100 -5.1700 | |
| D0131 | RAC-beta serine/threonine-protein kinase | P31751 | AKT2_HUMAN | RAC-PK-beta, Protein kinase B beta, Protein kinase Akt-2, PKB beta | AKT2 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (2X39) | 2X39 |
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Go to ligands | 43.5600 34.1500 110.6500 | |
| D0132 | Histone acetyltransferase p300 | Q09472 | EP300_HUMAN | p300 HAT, Protein propionyltransferase p300, P300, Histone crotonyltransferase p300, Histone butyryltransferase p300, E1Aassociated protein p300, E1A-associated protein p300 | Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. Mediates acetylation of histone H3 at 'Lys-122' (H3K122ac), a modification that localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability. Mediates acetylation of histone H3 at 'Lys-27' (H3K27ac). Also functions as acetyltransferase for non-histone targets, such as ALX1, HDAC1, PRMT1 or SIRT2. Acetylates 'Lys-131' of ALX1 and acts as its coactivator. Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function. Acetylates HDAC1 leading to its inactivation and modulation of transcription. Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2. Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium. Promotes cardiac myocyte enlargement. Can also mediate transcriptional repression. Acetylates FOXO1 and enhances its transcriptional activity. Acetylates BCL6 wich disrupts its ability to recruit histone deacetylases and hinders its transcriptional repressor activity. Participates in CLOCK or NPAS2-regulated rhythmic gene transcription, exhibits a circadian association with CLOCK or NPAS2, correlating with increase in PER1/2 mRNA and histone H3 acetylation on the PER1/2 promoter. Acetylates MTA1 at 'Lys-626' which is essential for its transcriptional coactivator activity. Acetylates XBP1 isoform 2, acetylation increases protein stability of XBP1 isoform 2 and enhances its transcriptional activity. Acetylates PCNA, acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER). Acetylates MEF2D. Acetylates and stabilizes ZBTB7B protein by antagonizing ubiquitin conjugation and degragation, this mechanism may be involved in CD4/CD8 lineage differentiation. In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA), butanoyl-CoA (butyryl-CoA) or propanoyl-CoA (propionyl-CoA), and is able to mediate protein crotonylation, butyrylation or propionylation, respectively. Acts as a histone crotonyltransferase, crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. Histone crotonyltransferase activity is dependent on the concentration of (2E)-butenoyl-CoA (crotonyl-CoA) substrate and such activity is weak when (E)-but-2-enoyl-CoA (crotonyl-CoA) concentration is low. Also acts as a histone butyryltransferase, butyrylation marks active promoters. Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway. Acetylates PCK1 and promotes PCK1 anaplerotic activity. Functions as histone acetyltransferase and regulates transcription via chromatin remodeling. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5LPM) | 5LPM |
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Go to ligands | 39.3300 7.7300 14.6500 | |
| D0133 | Cytochrome P450 2A6 | P11509 | CP2A6_HUMAN | Cytochrome P450(I), Cytochrome P450 IIA3, Coumarin 7-hydroxylase, CYPIIA6, CYP2A6, CYP2A3 | Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Possesses low phenacetin O-deethylation activity. | Enzyme | Oxidoreductase | Successful | ['02 Neoplasms', '14 Diseases of the skin'] | 2 | ['No clinical molecule'] | 0 | Downloaded from PDB (2FDV) | 2FDV |
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Go to ligands | 55.2600 78.3500 59.6100 | |
| D0134 | Glycoprotein IIb/IIIa receptor | P08514+P05106 | ITA2B_HUMAN+ITB3_HUMAN | Platelet membrane glycoprotein IIb, Platelet membrane glycoprotein IIIa, GP | Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha- IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface. | Receptor | - | Successful | ['11 Diseases of the circulatory system', '14 Diseases of the skin'] | 2 | ['11 Diseases of the circulatory system', '13 Diseases of the digestive system', '18 Pregnancy, childbirth or the puerperium'] | 3 | Downloaded from PDB (7UDH) | 7UDH |
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Go to ligands | 78.2400 95.2600 95.8100 | |
| D0135 | Histamine H4 receptor | Q9H3N8 | HRH4_HUMAN | SP9144, Pfi-013, HH4R, H4 receptor, GPRv53, GPCR105, G protein-coupled receptor 105, AXOR35 | Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist). The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['12 Diseases of the respiratory system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 3 | Modelled with SWISS-MODEL (7F61.1.A) | Homology |
|
Go to ligands | -20.1800 50.8500 -1.1000 | |
| D0136 | Voltage-gated calcium channel alpha Cav1.2 | Q13936 | CAC1C_HUMAN | Voltage-gated calcium channel subunit alpha Cav1.2, Voltage-dependent L-type calcium channel subunit alpha-1C, Calcium channel, L type, alpha-1 polypeptide, isoform 1, cardiac muscle, CCHL1A1, CACNL1A1, CACN2, CACH2 | Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm. Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm. Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. | Ion Channel | Channels/pores | Successful | ['11 Diseases of the circulatory system'] | 1 | ['08 Diseases of the nervous system'] | 1 | Modelled with SWISS-MODEL (7UHG.1.B) | Homology |
|
Go to ligands | 142.9500 157.1800 150.1800 | |
| D0137 | Rho-associated protein kinase 1 | Q13464 | ROCK1_HUMAN | Rok, Rho-associated, coiled-coil containing protein kinase 1, Rho-associated kinase 1, Rho kinase, ROCK1, ROCK, P160ROCK, P160(rock), P160 ROCK-1, Let-502 kinase | Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles. Promotes keratinocyte terminal differentiation. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization. | Enzyme | Transferase | Successful | ['09 Diseases of the visual system'] | 1 | ['01 Certain infectious or parasitic diseases', '11 Diseases of the circulatory system', '16 Diseases of the genitourinary system'] | 3 | Downloaded from PDB (3V8S) | 3V8S |
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Go to ligands | -43.3100 -56.7800 25.3800 | |
| D0138 | Adrenergic receptor beta-3 | P13945 | ADRB3_HUMAN | Beta3AR, Beta3-AR, Beta-3 adrenoreceptor, Beta-3 adrenoceptor, Beta-3 adrenergic receptor, B3AR, ADRB3R | Beta-3 is involved in the regulation of lipolysis and thermogenesis. Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. | Receptor | - | Successful | ['08 Diseases of the nervous system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '16 Diseases of the genitourinary system'] | 4 | ['05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '09 Diseases of the visual system', '16 Diseases of the genitourinary system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 5 | Modelled with SWISS-MODEL (7DH5.1.E) | Homology |
|
Go to ligands | 76.7600 74.1400 121.0800 | |
| D0139 | C-X-C chemokine receptor type 1 | P25024 | CXCR1_HUMAN | Interleukin-8 receptor A, IL8RA, IL-8R A, IL-8 receptor type 1, High affinity interleukin-8 receptor A, CXCR-1, CXC-R1, CMKAR1, CDw128a, CD181 | Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activate a phosphatidylinositol-calcium second messenger system. This receptor binds to IL-8 with a high affinity and to MGSA (GRO) with a low affinity. Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor. | Receptor | - | Successful | ['21 Symptoms, signs or clinical findings, not elsewhere classified'] | 1 | ['02 Neoplasms', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '22 Injury, poisoning or certain other consequences of external causes', '23 External causes of morbidity or mortality'] | 5 | Modelled with SWISS-MODEL (6LFO.1.E) | Homology |
|
Go to ligands | 126.8000 135.3400 170.8800 | |
| D0140 | Carbonic anhydrase VI | P23280 | CAH6_HUMAN | Secreted carbonic anhydrase, Salivary carbonic anhydrase, Carbonic anhydrase 6, Carbonate dehydratase VI | Its role in saliva is unknown. Reversible hydration of carbon dioxide. | Enzyme | Lyase | Successful | ['01 Certain infectious or parasitic diseases', '14 Diseases of the skin'] | 2 | ['02 Neoplasms'] | 1 | Downloaded from PDB (3FE4) | 3FE4 |
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Go to ligands | 28.4500 52.4300 81.4100 | |
| D0141 | Farnesoid X-activated receptor | Q96RI1 | NR1H4_HUMAN | Retinoid X receptor-interacting protein 14, RXR-interacting protein 14, RIP14, Nuclear receptor subfamily 1 group H member 4, HRR1, Farnesol receptor HRR-1, FXR, Bile acid receptor, BAR | Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response. The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in which the monomers are spaced by 1 nucleotide (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can be activated by either FXR or RXR-specific ligands. It is proposed that monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory nuclear responsive element (NRE) halfsites located in close proximity to FXREs modulate transcriptional activity (By similarity). In the liver activates transcription of the corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) implicating at least in part histone demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs). Activates transcription of the repressor MAFG (involved in regulation of BA synthesis) (By similarity). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine). In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression. The function also involves the coordinated induction of hepatic KLB/beta-klotho expression (By similarity). Regulates transcription of liver UGT2B4 and SULT2A1 involved in BA detoxification, binding to the UGT2B4 promoter seems to imply a monomeric transactivation independent of RXRA. Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, PPARA (involved in beta-oxidation of fatty acids), VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly. Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance). Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element. Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase). Involved in glucose homeostasis by modulating hepatic gluconeogenesis through activation of NR0B2/SHP-mediated repression of respective genes. Modulates glycogen synthesis (inducing phosphorylation of glycogen synthase kinase-3) (By similarity). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance. Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier (By similarity). Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells. Mediates trans-repression of TLR4-induced cytokine expression, the function seems to require its sumoylation and prevents N-CoR nuclear receptor corepressor clearance from target genes such as IL1B and NOS2. Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation, proposed to inhibit proinflammatory (but not antiapoptotic) NF-kappa-B signaling) (By similarity). | Nuclear Hormone Receptor | - | Successful | ['13 Diseases of the digestive system', '15 Diseases of the musculoskeletal system or connective tissue'] | 2 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '07 Sleep-wake disorders', '13 Diseases of the digestive system', '16 Diseases of the genitourinary system', '20 Developmental anomalies'] | 6 | Downloaded from PDB (6HL1) | 6HL1 |
|
Go to ligands | 11.0000 -13.6800 12.1400 | |
| D0142 | GABA A receptor alpha-2 | P47869 | GBRA2_HUMAN | GABRA2, GABA-A receptor alpha 2, GABA(A)Gamma-aminobutyric-acid receptor alpha-2 subunit precursor receptor | GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. | Receptor | - | Successful | ['23 External causes of morbidity or mortality'] | 1 | ['13 Diseases of the digestive system'] | 1 | Modelled with SWISS-MODEL (6HUO.1.A) | Homology |
|
Go to ligands | 131.0900 117.1600 166.2500 | |
| D0143 | GABA A receptor alpha-1 | P14867 | GBRA1_HUMAN | Gamma-aminobutyric acid receptor subunit alpha-1, GABA(A) receptor subunit alpha-1 | Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain. Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel. The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (By similarity). The alpha1/beta2/gamma2 receptor and the alpha1/beta3/gamma2 receptor exhibit synaptogenic activity. GABRA1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (By similarity). Functions also as histamine receptor and mediates cellular responses to histamine (By similarity). | Receptor | - | Successful | ['01 Certain infectious or parasitic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '08 Diseases of the nervous system', '09 Diseases of the visual system', '12 Diseases of the respiratory system', '16 Diseases of the genitourinary system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 8 | ['08 Diseases of the nervous system', '13 Diseases of the digestive system'] | 2 | Downloaded from PDB (6X3T) | 6X3T |
|
Go to ligands | 129.7700 116.8600 152.9800 | |
| D0144 | Gastric H+/K+ ATPase alpha | P20648 | ATP4A_HUMAN | Gastric H+/K+ ATPase alpha subunit, Gastric H(+)/K(+)-ATPase, ATP4A | Catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. Responsible for acid production in the stomach. | Enzyme | Hydrolase | Successful | ['01 Certain infectious or parasitic diseases', '13 Diseases of the digestive system'] | 2 | ['13 Diseases of the digestive system'] | 1 | Modelled with SWISS-MODEL (5YLV.1.A) | Homology |
|
Go to ligands | 49.9700 -14.9600 -6.5100 | |
| D0145 | Cholecystokinin receptor type A | P32238 | CCKAR_HUMAN | CCKAR, CCK-AR, CCK-A receptor | Receptor forcholecystokinin. Mediates pancreatic growth and enzyme secretion, smooth muscle contraction of the gall bladder and stomach. Has a 1000-fold higher affinity for CCK rather than for gastrin. It modulates feeding and dopamine-induced behavior in the central and peripheral nervous system. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '13 Diseases of the digestive system'] | 2 | Downloaded from PDB (7F8Y) | 7F8Y |
|
Go to ligands | 5.5400 21.8900 54.4000 | |
| D0146 | Matrix metalloproteinase-1 | P03956 | MMP1_HUMAN | Interstitial collagenase, Fibroblast collagenase, CLG | Cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity. Cleaves collagens of types I, II, and III at one site in the helical domain. | Enzyme | Hydrolase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '15 Diseases of the musculoskeletal system or connective tissue'] | 2 | Downloaded from PDB (966C) | 966C |
|
Go to ligands | 7.9300 -6.4200 37.4600 | |
| D0147 | Kinesin-like protein KIF11 | P52732 | KIF11_HUMAN | Thyroid receptor interacting protein 5, TRIP5, Kinesin-related motor protein Eg5, Kinesin-like spindle protein HKSP, Kinesin-like protein 1, KIF11, Eg5 | Required in non-mitotic cells for transport of secretory proteins from the Golgi complex to the cell surface. Motor protein required for establishing a bipolar spindle during mitosis. | Other | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6G6Y) | 6G6Y |
|
Go to ligands | 10.8300 19.7000 -0.8000 | |
| D0148 | Serine/threonine-protein kinase Chk2 | O96017 | CHK2_HUMAN | hCds1, Hucds1, Checkpoint kinase 2, Cds1 homolog, Cds1, CHK2 checkpoint homolog, CHK2 | May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition. Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (2YCF) | 2YCF |
|
Go to ligands | 48.0300 12.3500 -4.6900 | |
| D0149 | Adrenergic receptor beta-2 | P07550 | ADRB2_HUMAN | Beta-2 adrenoreceptor, Beta-2 adrenoceptor, Beta-2 adrenergic receptor, B2AR, ADRB2R | The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine. Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. | Receptor | - | Successful | ['07 Sleep-wake disorders', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '18 Pregnancy, childbirth or the puerperium'] | 4 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '11 Diseases of the circulatory system', '14 Diseases of the skin', '16 Diseases of the genitourinary system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 7 | Downloaded from PDB (6PS2) | 6PS2 |
|
Go to ligands | 1.5500 4.1800 50.8400 | |
| D0150 | Histone deacetylase 8 | Q9BY41 | HDAC8_HUMAN | Histone deacetylase-8, HDACL1, HD8, CDA07 | Gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility. Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5VI6) | 5VI6 |
|
Go to ligands | 6.7300 -4.9400 -23.2600 | |
| D0151 | Carbonic anhydrase IV | P22748 | CAH4_HUMAN | Carbonic anhydrase 4, Carbonate dehydratase IV, CAIV | May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid. Reversible hydration of carbon dioxide. | Enzyme | Lyase | Successful | ['01 Certain infectious or parasitic diseases', '09 Diseases of the visual system', '14 Diseases of the skin'] | 3 | ['02 Neoplasms', '12 Diseases of the respiratory system'] | 2 | Downloaded from PDB (3FW3) | 3FW3 |
|
Go to ligands | 17.6000 -1.5800 -17.8200 | |
| D0152 | Platelet-derived growth factor receptor alpha | P16234 | PGFRA_HUMAN | RHEPDGFRA, Platelet-derived growth factor receptor 2, Platelet-derived growth factor alpha receptor, PDGFR2, PDGFR-alpha, PDGFR-2, PDGF-R-alpha, CD140a antigen, CD140a, CD140 antigen-like family member A, Alpha-type platelet-derived growth factor receptor, Alpha platelet-derived growth factor receptor | Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades, the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. | Enzyme | Transferase | Successful | ['02 Neoplasms', '03 Diseases of the blood or blood-forming organs'] | 2 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5GRN) | 5GRN |
|
Go to ligands | -13.1400 2.9300 -10.2900 | |
| D0153 | Neuromedin-K receptor | P29371 | NK3R_HUMAN | Tachykinin receptor 3, TACR3, Neuromedin K receptor, Neurokinin-3 receptor, Neurokinin B receptor, NKR, NK-3R, NK-3 receptor | This is a receptor for the tachykinin neuropeptide neuromedin-K (neurokinin B). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: neuromedin-K > substance K > substance P. | Receptor | - | Successful | ['16 Diseases of the genitourinary system'] | 1 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system'] | 2 | Modelled with AlphaFold (AF-P29371-F1-model_v4) | Ab initio |
|
Go to ligands | -12.0400 1.2900 2.0200 | |
| D0154 | cAMP-dependent chloride channel F508 deletion | P13569 | CFTR_HUMAN | cAMP-dependent chloride channel (del F508), Cystic fibrosis transmembrane conductance regulator (del F508), Channel conductance-controlling ATPase, CFTR, ATP-binding cassette sub-family C member 7 (del F508), ABCC7 (del F508) | Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis. Mediates the transport of chloride ions across the cell membrane. Channel activity is coupled to ATP hydrolysis. The ion channel is also permeable to HCO(3-), selectivity depends on the extracellular chloride concentration. Exerts its function also by modulating the activity of other ion channels and transporters. Plays an important role in airway fluid homeostasis. Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens. Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex. Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G. Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7. Can inhibit the chloride channel activity of ANO1. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation. | Transporter | Primary Active Transporters | Successful | ['12 Diseases of the respiratory system', '22 Injury, poisoning or certain other consequences of external causes'] | 2 | ['No clinical molecule'] | 0 | Downloaded from PDB (5TFJ) | 5TFJ |
|
Go to ligands | -20.8000 -9.7400 -11.9200 | |
| D0155 | Dopamine transporter | Q01959 | SC6A3_HUMAN | Solute carrier family 6 member 3, Sodium-dependent dopamine transporter, DAT1, DAT, DA transporter | Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals. | Transporter | Electrochemical Potential-driven Transporters | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '08 Diseases of the nervous system', '09 Diseases of the visual system'] | 5 | ['06 Mental, behavioural or neurodevelopmental disorders', '13 Diseases of the digestive system', '22 Injury, poisoning or certain other consequences of external causes'] | 3 | Modelled with SWISS-MODEL (6VRH.1.A) | Homology |
|
Go to ligands | 134.5600 123.2500 122.0300 | |
| D0156 | Prostaglandin E synthase | O14684 | PTGES_HUMAN | p53-induced gene 12 protein, PIG12, PGES, PGE synthase, P53-induced apoptosis protein 12, Microsomal prostaglandin E synthase 1, Microsomal glutathione S-transferase 1-like 1, MPGES1, MPGES-1, MGST1L1, MGST1-L1 | Catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2). | Enzyme | Oxidoreductase | Clinical trial | ['No approved drug'] | 0 | ['08 Diseases of the nervous system'] | 1 | Downloaded from PDB (5TL9) | 5TL9 |
|
Go to ligands | 8.4500 -12.0900 32.3200 | |
| D0157 | C-C chemokine receptor type 4 | P51679 | CCR4_HUMAN | K5-5, CMKBR4, CD194, CCR-4, CC-CKR-4, CC chemokine receptor 4, C-CCKR-4, C-C CKR-4 | The activity of this receptor is mediated by G(i) proteins which activate a phosphatidylinositol-calcium second messenger system. Can function as a chemoattractant homing receptor on circulating memory lymphocytes and as a coreceptor for some primary HIV-2 isolates. In the CNS, could mediate hippocampal-neuron survival. High affinity receptor for the C-C type chemokines CCL17/TARC, CCL22/MDC and CKLF isoform 1/CKLF1. | Receptor | - | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '04 Diseases of the immune system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system'] | 4 | Modelled with SWISS-MODEL (7O7F.1.C) | Homology |
|
Go to ligands | 190.5800 182.3100 228.7500 | |
| D0158 | ALK tyrosine kinase receptor | Q9UM73 | ALK_HUMAN | CD246, Anaplastic lymphoma kinase | Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK. Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4Z55) | 4Z55 |
|
Go to ligands | -20.3900 12.4000 -10.3300 | |
| D0159 | ATP-binding cassette transporter G2 | Q9UNQ0 | ABCG2_HUMAN | Urate exporter, Placenta-specific ATP-binding cassette transporter, Mitoxantrone resistance-associated protein, MXR, CDw338, CD338, Breast cancer resistance protein, BCRP1, BCRP, ABCP | Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. Implicated in the efflux of numerous drugs and xenobiotics: mitoxantrone, the photosensitizer pheophorbide, camptothecin, methotrexate, azidothymidine (AZT), and the anthracyclines daunorubicin and doxorubicin. High-capacity urate exporter functioning in both renal and extrarenal urate excretion. | Transporter | Primary Active Transporters | Successful | ['13 Diseases of the digestive system', '15 Diseases of the musculoskeletal system or connective tissue'] | 2 | ['No clinical molecule'] | 0 | Downloaded from PDB (6ETI) | 6ETI |
|
Go to ligands | 151.1200 163.2400 163.3400 | |
| D0160 | C-X-C chemokine receptor type 2 | P25025 | CXCR2_HUMAN | Interleukin-8 receptor B, IL8RB, IL-8R B, IL-8 receptor type 2, High affinity interleukin-8 receptor B, GRO/MGSA receptor, CXCR-2, CXC-R2, CDw128b, CD182 | Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Binds to IL-8 with high affinity. Also binds with high affinity to CXCL3, GRO/MGSA and NAP-2. Receptor for interleukin-8 which is a powerful neutrophil chemotactic factor. | Receptor | - | Successful | ['01 Certain infectious or parasitic diseases', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 2 | ['02 Neoplasms', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '22 Injury, poisoning or certain other consequences of external causes', '23 External causes of morbidity or mortality'] | 6 | Downloaded from PDB (6LFO) | 6LFO |
|
Go to ligands | 132.7500 142.8000 143.8000 | |
| D0161 | Debrisoquine 4-hydroxylase | P10635 | CP2D6_HUMAN | P450-DB1, Cytochrome P450-DB1, Cytochrome P450 2D6, CYPIID6, CYP2DL1 | It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants. Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. | Enzyme | Oxidoreductase | Successful | ['07 Sleep-wake disorders'] | 1 | ['01 Certain infectious or parasitic diseases'] | 1 | Downloaded from PDB (3TBG) | 3TBG |
|
Go to ligands | 8.1400 24.1800 -7.2900 | |
| D0162 | Lysosomal alpha-glucosidase | P10253 | LYAG_HUMAN | GAA, Aglucosidase alfa, Acid maltase | Essential for the degradation of glygogen to glucose in lysosomes. | Enzyme | Hydrolase | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['No clinical molecule'] | 0 | Downloaded from PDB (5NN5) | 5NN5 |
|
Go to ligands | -13.0200 -30.2100 96.1500 | |
| D0163 | Tyrosine-protein kinase Kit | P10721 | KIT_HUMAN | v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog, p145 c-kit, Proto-oncogene tyrosine-protein kinase Kit, Proto-oncogene c-Kit, Piebald trait protein, PBT, Mast/stem cell growth factor receptor Kit, CD117 antigen, CD117, C-kit | In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1. Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. | Enzyme | Transferase | Successful | ['02 Neoplasms', '03 Diseases of the blood or blood-forming organs'] | 2 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '08 Diseases of the nervous system', '15 Diseases of the musculoskeletal system or connective tissue', '20 Developmental anomalies', '24 Factors influencing health status or contact with health services'] | 6 | Downloaded from PDB (3G0E) | 3G0E |
|
Go to ligands | 35.3600 -6.3400 -77.6400 | |
| D0164 | Peroxisome proliferator-activated receptor gamma | P37231 | PPARG_HUMAN | PPAR-gamma, Nuclear receptor subfamily 1 group C member 3, NR1C3 | Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity). | Nuclear Hormone Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '08 Diseases of the nervous system'] | 2 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '09 Diseases of the visual system', '13 Diseases of the digestive system', '15 Diseases of the musculoskeletal system or connective tissue'] | 7 | Downloaded from PDB (2Q59) | 2Q59 |
|
Go to ligands | -33.3400 -8.4900 -38.2100 | |
| D0165 | Opioid receptor delta | P41143 | OPRD_HUMAN | OPRD, Delta-type opioid receptor, Delta opioid receptor, DOR-1, D-OR-1 | Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine. G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. | Receptor | - | Successful | ['13 Diseases of the digestive system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 2 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 6 | Downloaded from PDB (6PT3) | 6PT3 |
|
Go to ligands | 3.9500 -40.8900 -44.5800 | |
| D0166 | Platelet-derived growth factor receptor beta | P09619 | PGFRB_HUMAN | Platelet-derived growth factor receptor 1, PDGFR1, PDGFR-beta, PDGFR-1, PDGFR, PDGF-R-beta, CD140b antigen, CD140b, CD140 antigen-like family member B, Beta-type platelet-derived growth factor receptor, Beta-PDGFR, Beta platelet-derived growth factor receptor | Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to the activation of several signaling cascades, the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. | Enzyme | Transferase | Successful | ['02 Neoplasms', '03 Diseases of the blood or blood-forming organs', '05 Endocrine. Nutritional or metabolic diseases'] | 3 | ['02 Neoplasms', '08 Diseases of the nervous system', '22 Injury, poisoning or certain other consequences of external causes'] | 3 | Downloaded from PDB (3MJG) | 3MJG |
|
Go to ligands | 17.8000 -26.4400 -39.0900 | |
| D0167 | Sphingosine kinase 2 | Q9NRA0 | SPHK2_HUMAN | SPK 2, SK 2 | Acts on D-erythro-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides. Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Modelled with AlphaFold (AF-Q9NRA0-F1-model_v4) | Ab initio |
|
Go to ligands | -19.2400 7.7400 5.2600 | |
| D0168 | Epidermal growth factor receptor | P00533 | EGFR_HUMAN | Receptor tyrosine-protein kinase erbB-1, Proto-oncogene c-ErbB-1, HER1, ERBB1, ERBB | Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. Plays a role in enhancing learning and memory performance (By similarity). | Enzyme | Transferase | Successful | ['02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '22 Injury, poisoning or certain other consequences of external causes'] | 4 | ['02 Neoplasms', '08 Diseases of the nervous system', '14 Diseases of the skin', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 4 | Downloaded from PDB (8A27) | 8A27 |
|
Go to ligands | 21.3800 -10.6700 -9.8300 | |
| D0169 | D-amino acid oxidase | P14920 | OXDA_HUMAN | Daminoacid oxidase, DAMOX, DAAO | Regulates the level of the neuromodulator D-serine in the brain. Has high activity towards D-DOPA and contributes to dopamine synthesis. Could act as a detoxifying agent which removes D-amino acids accumulated during aging. Acts on a variety of D-amino acids with a preference for those having small hydrophobic side chains followed by those bearing polar, aromatic, and basic groups. Does not act on acidic amino acids. | Enzyme | Oxidoreductase | Clinical trial | ['No approved drug'] | 0 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system'] | 2 | Downloaded from PDB (7U9U) | 7U9U |
|
Go to ligands | -17.2300 7.8800 -35.4800 | |
| D0170 | Glucagon receptor | P47871 | GLR_HUMAN | GLR, GL-R | Regulates the rate of hepatic glucose production by promoting glycogen hydrolysis and gluconeogenesis. Plays an important role in mediating the responses to fasting. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Promotes activation of adenylate cyclase. Besides, plays a role in signaling via a phosphatidylinositol-calcium second messenger system. G-protein coupled receptor for glucagon that plays a central role in the regulation of blood glucose levels and glucose homeostasis. | Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['05 Endocrine, nutritional or metabolic diseases', '13 Diseases of the digestive system'] | 2 | Downloaded from PDB (5EE7) | 5EE7 |
|
Go to ligands | -23.3100 3.3800 -32.7900 | |
| D0171 | Prostaglandin G/H synthase 1 | P23219 | PGH1_HUMAN | Prostaglandin-endoperoxide synthase 1, Prostaglandin H2 synthase 1, PHS 1, PGHS-1, PGH synthase 1, Cyclooxygenase-1, COX1, COX-1 | Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells. | Enzyme | Oxidoreductase | Successful | ['01 Certain infectious or parasitic diseases', '05 Endocrine. Nutritional or metabolic diseases', '13 Diseases of the digestive system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system', '20 Developmental anomalies', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 8 | ['02 Neoplasms', '04 Diseases of the immune system', '08 Diseases of the nervous system', '15 Diseases of the musculoskeletal system or connective tissue'] | 4 | Downloaded from PDB (6Y3C) | 6Y3C |
|
Go to ligands | -35.1700 -38.4600 9.9800 | |
| D0172 | Tropomyosin-related kinase A | P04629 | NTRK1_HUMAN | gp140trk, Tyrosine kinase receptor A, Tyrosine kinase receptor, Trk-A, TRKA, TRK1-transforming tyrosine kinase protein, TRK1 transforming tyrosinekinase protein, TRK, P140-TrkA, Neurotrophic tyrosine kinase receptor type 1, NGF-trk receptor type A, MTC, High affinity nerve growth factor receptor | High affinity receptor for NGF which is its primary ligand. Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival. Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors. Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '08 Diseases of the nervous system', '14 Diseases of the skin'] | 3 | Downloaded from PDB (5JFW) | 5JFW |
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Go to ligands | -18.2800 -40.5500 -3.6400 | |
| D0173 | Thyrotropin receptor | P16473 | TSHR_HUMAN | Thyroid stimulating hormone receptor, TSHR, TSH-R, TSH receptor | Receptor for thyrothropin. Plays a central role in controlling thyroid cell metabolism. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Also acts as a receptor for thyrostimulin (gpa2+gpb5). | Receptor | - | Successful | ['02 Neoplasms', '05 Endocrine. Nutritional or metabolic diseases'] | 2 | ['No clinical molecule'] | 0 | Downloaded from PDB (7T9M) | 7T9M |
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Go to ligands | 148.0700 137.4400 163.6900 | |
| D0174 | Proto-oncogene c-Ret | P07949 | RET_HUMAN | RET51, RET receptor tyrosine kinase, RET mutant Y791F, RET mutant V804M, RET mutant V804L, RET mutant S891A, RET mutant M918T, RET mutant G691S, Proto-oncogene tyrosine-protein kinase receptor Ret, PTC, Cadherin family member 12, CDHR16, CDHF12, C-ret | Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis, involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e. g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor, in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers, these diseases are characterized by aberrant integrins-regulated cell migration. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways. Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL. Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. | Enzyme | Transferase | Successful | ['02 Neoplasms', '03 Diseases of the blood or blood-forming organs'] | 2 | ['02 Neoplasms', '13 Diseases of the digestive system'] | 2 | Downloaded from PDB (7DUA) | 7DUA |
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Go to ligands | 8.5600 -1.9400 -2.0400 | |
| D0175 | Opioid receptor kappa | P41145 | OPRK_HUMAN | OPRK, Kappa-type opioid receptor, Kappa opioid receptor, KOR-1, KOR, K-OR-1 | Functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions. G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. | Receptor | - | Successful | ['14 Diseases of the skin', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 2 | ['06 Mental, behavioural or neurodevelopmental disorders', '11 Diseases of the circulatory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 5 | Downloaded from PDB (8DZR) | 8DZR |
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Go to ligands | 131.3700 134.3800 155.4000 | |
| D0176 | Matrix metalloproteinase-13 | P45452 | MMP13_HUMAN | Matrix metalloproteinase 13, Collagenase-3, Collagenase 3 | Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CTGF. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CTGF. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion. Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '15 Diseases of the musculoskeletal system or connective tissue', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 3 | Downloaded from PDB (3ZXH) | 3ZXH |
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Go to ligands | 22.0100 4.2200 61.9300 | |
| D0177 | Dihydrodiol dehydrogenase type I | P42330 | AK1C3_HUMAN | Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase, Testosterone 17-beta-dehydrogenase 5, Prostaglandin F synthase, PGFS, KIAA0119, Indanol dehydrogenase, HSD17B5, HA1753, Dihydrodiol dehydrogenase 3, DDH1, DD3, DD-3, Chlordecone reductase homolog HAKRb, Aldo-keto reductase family 1 member C3, 3-alpha-hydroxysteroid dehydrogenase type 2, 3-alpha-HSD type II, brain, 3-alpha-HSD type 2, 17-beta-hydroxysteroid dehydrogenase type 5, 17-beta-HSD 5 | Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone. | Enzyme | Oxidoreductase | Successful | ['16 Diseases of the genitourinary system'] | 1 | ['02 Neoplasms'] | 1 | Downloaded from PDB (1S1P) | 1S1P |
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Go to ligands | 25.4800 -26.1600 60.6100 | |
| D0178 | Dihydroorotate dehydrogenase | Q02127 | PYRD_HUMAN | Dihydroorotate oxidase, Dihydroorotate dehydrogenase (quinone), mitochondrial, DHOdehase, DHODH | Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. | Enzyme | Oxidoreductase | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '08 Diseases of the nervous system'] | 2 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '13 Diseases of the digestive system', '15 Diseases of the musculoskeletal system or connective tissue'] | 4 | Downloaded from PDB (4OQV) | 4OQV |
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Go to ligands | 4.5400 -35.8700 -2.3100 | |
| D0179 | Angiotensinogenase renin | P00797 | RENI_HUMAN | Renin, Angiotensinogenase | Renin is a highly specific endopeptidase, whose only knownfunction is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney. | Enzyme | Hydrolase | Successful | ['11 Diseases of the circulatory system'] | 1 | ['05 Endocrine, nutritional or metabolic diseases', '09 Diseases of the visual system', '11 Diseases of the circulatory system', '13 Diseases of the digestive system'] | 4 | Downloaded from PDB (3K1W) | 3K1W |
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Go to ligands | -8.2900 -14.8600 -10.1200 | |
| D0180 | Phosphodiesterase 4A | P27815 | PDE4A_HUMAN | cAMP-specific 3',5'-cyclic phosphodiesterase 4A, Type 4A cAMP phosphodiesterase, PDE46, DPDE2 | Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. | Enzyme | Hydrolase | Successful | ['12 Diseases of the respiratory system'] | 1 | ['05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 7 | Downloaded from PDB (2QYK) | 2QYK |
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Go to ligands | 88.3200 41.0700 17.8500 | |
| D0181 | Soluble epoxide hydrolase | P34913 | HYES_HUMAN | Bifunctional epoxide hydrolase 2 | Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides (By similarity). Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid and 12-phosphonooxy-octadec-9E-enoic acid. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['11 Diseases of the circulatory system', '12 Diseases of the respiratory system'] | 2 | Downloaded from PDB (4JNC) | 4JNC |
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Go to ligands | -13.0200 27.2700 -13.2200 | |
| D0182 | ERK activator kinase 1 | Q02750 | MP2K1_HUMAN | PRKMK1, Mitogen-activated protein kinase kinase 1, MKK1, MEK 1, MAPKK 1, MAPK/ERKkinase 1, MAPK/ERK kinase 1, MAP kinase kinase 1, Dual specificity mitogen-activated protein kinase kinase 1 | Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis. Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (7B7R) | 7B7R |
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Go to ligands | -32.2500 7.9600 -7.2500 | |
| D0183 | Adenosine A3 receptor | P0DMS8 | AA3R_HUMAN | Adenosine receptor A3A, Adenosine receptor A3, Adenosine 3 receptor, A3AR, A3 Adenosine receptor | The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. Isoform 2: Receptor for adenosine. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 6 | Modelled with SWISS-MODEL (7LD3.1.B) | Homology |
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Go to ligands | 86.5600 117.6200 122.4200 | |
| D0184 | Glutamate receptor ionotropic NMDA 1 | Q05586 | NMDZ1_HUMAN | NmethylDaspartate receptor subunit NR1, NMDR1, NMD-R1, N-methyl-D-aspartate receptor subunit NR1, Glutamate receptor ionotropic, NMDA 1, Glutamate [NMDA] receptor subunit zeta1, Glutamate [NMDA] receptor subunit zeta-1, GluN1 | Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition. Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. | Receptor | - | Successful | ['01 Certain infectious or parasitic diseases'] | 1 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system'] | 2 | Downloaded from PDB (5H8Q) | 5H8Q |
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Go to ligands | 9.8500 -15.5700 -27.4600 | |
| D0185 | GABA A receptor alpha-3 | P34903 | GBRA3_HUMAN | Gamma-aminobutyric acid receptor subunit alpha-3, GABA-A receptor alpha 3, GABA(A)Gamma-aminobutyric-acid receptor alpha-3 subunit precursor receptor, GABA(A) receptor subunit alpha-3 | GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. | Receptor | - | Successful | ['23 External causes of morbidity or mortality'] | 1 | ['06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '13 Diseases of the digestive system'] | 3 | Modelled with SWISS-MODEL (6HUG.1.A) | Homology |
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Go to ligands | 130.3600 137.4900 107.7300 | |
| D0186 | Peroxisome proliferator-activated receptor delta | Q03181 | PPARD_HUMAN | Peroxisomeproliferator-activated receptor beta, Peroxisomeproliferator activated receptor beta/delta, Peroxisome proliferator-activated receptor beta, PPARdelta, PPARB, PPAR-delta, PPAR-beta, Nuclear receptor subfamily 1 group C member 2, Nuclear hormone receptor 1, NUCI, NUC1, NR1C2 | Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand. Ligand-activated transcription factor. | Nuclear Hormone Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '13 Diseases of the digestive system'] | 3 | Downloaded from PDB (5Y7X) | 5Y7X |
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Go to ligands | -2.6100 19.2600 8.3200 | |
| D0187 | Tyrosine-protein kinase SYK | P43405 | KSYK_HUMAN | p72-Syk, Spleen tyrosine kinase | Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR plays also a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade. Required for the stimulation of neutrophil phagocytosis by IL15. Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils. Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response. Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). | Enzyme | Transferase | Successful | ['03 Diseases of the blood or blood-forming organs'] | 1 | ['02 Neoplasms', '12 Diseases of the respiratory system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 4 | Downloaded from PDB (4YJR) | 4YJR |
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Go to ligands | 31.0800 37.0300 31.7100 | |
| D0188 | Bacterial Dihydrofolate reductase | P0ABQ4 | DYR_ECOLI | Bact Dihydrofolate reductase | Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. | Enzyme | Oxidoreductase | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '12 Diseases of the respiratory system'] | 2 | Downloaded from PDB (6MT8) | 6MT8 |
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Go to ligands | -20.0400 -1.9900 -9.1100 | |
| D0189 | Vascular endothelial growth factor receptor 3 | P35916 | VGFR3_HUMAN | VEGFR3, VEGFR-3, VEGF-3 receptor, Tyrosine-protein kinase receptor FLT4, Fms-like tyrosine kinase 4 | Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades, isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'. Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system'] | 3 | Downloaded from PDB (4BSJ) | 4BSJ |
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Go to ligands | 26.5100 59.1400 7.6100 | |
| D0190 | Janus kinase 1 | P23458 | JAK1_HUMAN | Tyrosine-protein kinase JAK1, JAK1B, JAK1A | Kinase partner for the interleukin (IL)-2 receptor as well as interleukin (IL)-10 receptor. Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. | Enzyme | Transferase | Successful | ['02 Neoplasms', '03 Diseases of the blood or blood-forming organs', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 4 | ['02 Neoplasms', '04 Diseases of the immune system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 6 | Downloaded from PDB (6N7A) | 6N7A |
|
Go to ligands | 14.6700 26.1800 20.3500 | |
| D0191 | Tyrosine-protein kinase ABL1 | P00519 | ABL1_HUMAN | p150, Proto-oncogene tyrosine-protein kinase ABL1, Proto-oncogene c-Abl, JTK7, C-ABL, Abl, Abelson tyrosine-protein kinase 1, Abelson murine leukemia viral oncogene homolog 1 | Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation), ANXA1 (involved in membrane anchoring), DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling), or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717'. ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E. coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H. pylori, or AnkA (ankyrin repeat-containing protein A) of A. phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner. Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity. Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. | Enzyme | Transferase | Successful | ['02 Neoplasms', '05 Endocrine. Nutritional or metabolic diseases', '08 Diseases of the nervous system'] | 3 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system'] | 4 | Downloaded from PDB (5HU9) | 5HU9 |
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Go to ligands | -5.5100 -27.9500 -16.6500 | |
| D0192 | Cathepsin A | P10619 | PPGB_HUMAN | Protective protein for betagalactosidase, Protective protein cathepsin A, PPCA, Lysosomal protective protein 20 kDa chain, Lysosomal protective protein, Carboxypeptidase L, Carboxypeptidase C, CTSA | Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases'] | 1 | Downloaded from PDB (4CIB) | 4CIB |
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Go to ligands | -32.2500 10.2100 16.1600 | |
| D0193 | Vascular endothelial growth factor receptor 1 | P17948 | VGFR1_HUMAN | Vascular permeability factor receptor, VEGFR1, VEGFR-1, VEGF-1 receptor, Tyrosine-protein kinase receptor FLT, Tyrosine-protein kinase FRT, Fms-like tyrosine kinase 1, FRT, FL | May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity, may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain, it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion. Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '09 Diseases of the visual system', '11 Diseases of the circulatory system'] | 3 | Downloaded from PDB (3HNG) | 3HNG |
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Go to ligands | 4.4900 19.0700 33.5000 | |
| D0194 | Nitric-oxide synthase inducible | P35228 | NOS2_HUMAN | iNOS, Peptidyl-cysteine S-nitrosylase NOS2, Nitric oxide synthase, inducible, NOS2A, NOS type II, Inducible NOS, Inducible NO synthase, Hepatocyte NOS, HEP-NOS | Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2 (By similarity). As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on 'Cys-247' implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM. Involved in inflammation, enhances the synthesis of proinflammatory mediators such as IL6 and IL8. | Enzyme | Oxidoreductase | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '09 Diseases of the visual system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 8 | Downloaded from PDB (3E7G) | 3E7G |
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Go to ligands | -0.1200 35.0400 35.3000 | |
| D0195 | Neuronal acetylcholine receptor alpha-4/beta-2 | P43681+P17787 | ACHA4_HUMAN+ACHB2_HUMAN | CHRN, nAChR | After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodiun ions. | Receptor | - | Successful | ['06 Mental, behavioural or neurodevelopmental disorders', '09 Diseases of the visual system'] | 2 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '13 Diseases of the digestive system'] | 3 | Downloaded from PDB (5KXI) | 5KXI |
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Go to ligands | 67.3900 -27.3000 -40.4400 | |
| D0196 | Albendazole monooxygenase | P08684 | CP3A4_HUMAN | Taurochenodeoxycholate 6-alpha-hydroxylase, Quinine 3-monooxygenase, P450-PCN1, Nifedipine oxidase, NF-25, HLp, Cytochrome P450-PCN1, Cytochrome P450 NF-25, Cytochrome P450 HLp, Cytochrome P450 3A4, Cytochrome P450 3A3, CYPIIIA4, CYPIIIA3, CYP3A3, Albendazole sulfoxidase, Albendazole monooxygenase (sulfoxide-forming), 1,8-cineole 2-exo-monooxygenase | In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e. g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide. Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole. Cytochromes P450 are a group of heme-thiolate monooxygenases. | Enzyme | Oxidoreductase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '14 Diseases of the skin'] | 2 | Downloaded from PDB (4D6Z) | 4D6Z |
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Go to ligands | 17.7300 30.0900 -11.1100 | |
| D0197 | 5-HT 3A receptor | P46098 | 5HT3A_HUMAN | Serotonin-gated ion channel receptor, Serotonin receptor 3A, HTR3, 5HT3R, 5-hydroxytryptamine receptor 3A, 5-HT3RA, 5-HT3A, 5-HT3-A, 5-HT 3A | This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel. | Receptor | - | Successful | ['08 Diseases of the nervous system', '09 Diseases of the visual system', '13 Diseases of the digestive system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 4 | ['No clinical molecule'] | 0 | Modelled with SWISS-MODEL (6NP0.1.A) | Homology |
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Go to ligands | 156.7200 134.2000 123.7700 | |
| D0198 | Histamine H3 receptor | Q9Y5N1 | HRH3_HUMAN | Histamine receptor 3, HH3R, GPCR97, G-protein coupled receptor 97, G protein-coupled receptor 97 | Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization. The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. | Receptor | - | Successful | ['21 Symptoms, signs or clinical findings, not elsewhere classified'] | 1 | ['05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '08 Diseases of the nervous system', '12 Diseases of the respiratory system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 6 | Downloaded from PDB (7F61) | 7F61 |
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Go to ligands | -19.9400 49.1700 -0.3600 | |
| D0199 | Voltage-gated calcium channel alpha Cav3.1 | O43497 | CAC1G_HUMAN | Voltage-gated calcium channel alpha subunit Cav3.1, Voltage-dependent T-type calcium channel, NBR13, Cav3.1c, CACNA1G | Voltage-sensitive calcium channels (vscc) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release and gene expression. | Ion Channel | Channels/pores | Successful | ['02 Neoplasms', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '20 Developmental anomalies'] | 5 | ['07 Sleep-wake disorders'] | 1 | Downloaded from PDB (6KZP) | 6KZP |
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Go to ligands | 170.9100 174.8600 182.6900 | |
| D0200 | Somatostatin receptor type 5 | P35346 | SSR5_HUMAN | Somatostatin receptor 5, SSTR5, SS5R | Receptor for somatostatin 28 and to a lesser extent for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Increases cell growth inhibition activity of SSTR2 following heterodimerization. | Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['No clinical molecule'] | 0 | Modelled with SWISS-MODEL (7UL5.1.A) | Homology |
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Go to ligands | 139.1200 136.4400 149.3300 | |
| D0201 | Ubiquitin-protein ligase E3 Mdm2 | Q00987 | MDM2_HUMAN | RING-type E3 ubiquitin transferase Mdm2, P53-binding protein Mdm2, Oncoprotein Mdm2, MDM2 protein, Hdm2, E3 ubiquitin-protein ligase Mdm2, Double minute 2 protein | Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation. Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells. Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis. E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6Q96) | 6Q96 |
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Go to ligands | -19.4400 -5.6700 6.1000 | |
| D0202 | Coagulation factor XII | P00748 | FA12_HUMAN | Hageman factor, HAF | Unavailable | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['04 Diseases of the immune system', '13 Diseases of the digestive system'] | 2 | Downloaded from PDB (6X0T) | 6X0T |
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Go to ligands | 16.7300 -30.6400 14.7000 | |
| D0203 | dUTP pyrophosphatase | P33316 | DUT_HUMAN | Deoxyuridine 5' triphosphate nucleotidohydrolase, mitochondrial, DUT | This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA. {ECO:0000269|PubMed:8805593}. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (3ARA) | 3ARA |
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Go to ligands | 6.7600 11.3600 -10.9400 | |
| D0204 | Ras-related protein Rab-9A | P51151 | RAB9A_HUMAN | RAB9A | Involved in the transport of proteins between the endosomes and the trans Golgi network. | Enzyme | Hydrolase | Successful | ['01 Certain infectious or parasitic diseases'] | 1 | ['No clinical molecule'] | 0 | Downloaded from PDB (1WMS) | 1WMS |
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Go to ligands | 0.9300 19.5300 10.1600 | |
| D0205 | Smoothened homolog | Q99835 | SMO_HUMAN | Smo-D473H, SMOH, Protein Gx | Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia. Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation. G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. | Receptor | - | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms'] | 1 | Downloaded from PDB (7ZI0) | 7ZI0 |
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Go to ligands | -29.2600 -23.2200 73.0000 | |
| D0206 | Prostaglandin G/H synthase 2 | P35354 | PGH2_HUMAN | Prostaglandin-endoperoxide synthase 2, Prostaglandin H2 synthase 2, PHS II, PGHS-2, PGH synthase 2, Cyclooxygenase-2, COX2, COX-2 | Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis. During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, that regulates phagocytic microglia (By similarity). | Enzyme | Oxidoreductase | Successful | ['01 Certain infectious or parasitic diseases', '05 Endocrine. Nutritional or metabolic diseases', '13 Diseases of the digestive system', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 6 | ['02 Neoplasms', '08 Diseases of the nervous system', '12 Diseases of the respiratory system', '15 Diseases of the musculoskeletal system or connective tissue'] | 4 | Downloaded from PDB (5F1A) | 5F1A |
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Go to ligands | 36.6500 18.5500 195.5300 | |
| D0207 | Dopamine D2 receptor | P14416 | DRD2_HUMAN | Dopamine receptor 2, D(2) dopamine receptor | Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. | Receptor | - | Successful | ['01 Certain infectious or parasitic diseases', '04 Diseases of the immune system', '05 Endocrine. Nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '08 Diseases of the nervous system', '09 Diseases of the visual system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '18 Pregnancy, childbirth or the puerperium', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 12 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '08 Diseases of the nervous system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '16 Diseases of the genitourinary system', '17 Conditions related to sexual health', '20 Developmental anomalies'] | 10 | Downloaded from PDB (6CM4) | 6CM4 |
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Go to ligands | 9.8200 6.3200 -7.2600 | |
| D0208 | Neurotensin receptor type 1 | P30989 | NTR1_HUMAN | NTSR1, NTRH, NTR1, NTR subtype 1, NT-R1, NT-R-1, High-affinity levocabastine-insensitive neurotensin receptor | G-protein coupled receptor for the tridecapeptide neurotensin (NTS). Signaling is effected via G proteins that activate a phosphatidylinositol-calcium second messenger system. Signaling leads to the activation of downstream MAP kinases and protects cells against apoptosis. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['13 Diseases of the digestive system'] | 1 | Downloaded from PDB (7UL2) | 7UL2 |
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Go to ligands | 152.2700 142.1700 123.8500 | |
| D0209 | Macrophage migration inhibitory factor | P14174 | MIF_HUMAN | Phenylpyruvate tautomerase, MMIF, L-dopachrome tautomerase, L-dopachrome isomerase, Glycosylation-inhibiting factor, GLIF, GIF | Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity. Pro-inflammatory cytokine. | Enzyme | Oxidoreductase | Clinical trial | ['No approved drug'] | 0 | ['03 Diseases of the blood or blood-forming organs', '05 Endocrine, nutritional or metabolic diseases'] | 2 | Downloaded from PDB (6B1K) | 6B1K |
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Go to ligands | -20.8400 -14.4100 15.8200 | |
| D0210 | Muscarinic acetylcholine receptor M3 | P20309 | ACM3_HUMAN | M3 receptor, CHRM3 | The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover. | Receptor | - | Successful | ['04 Diseases of the immune system', '09 Diseases of the visual system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '16 Diseases of the genitourinary system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 7 | ['No clinical molecule'] | 0 | Downloaded from PDB (8EA0) | 8EA0 |
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Go to ligands | 127.9900 121.1300 153.6500 | |
| D0211 | PI3-kinase delta | O00329 | PK3CD_HUMAN | PtdIns-3-kinase subunit p110-delta, PtdIns-3-kinase subunit delta, Phosphoinositide 3-kinase delta, Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, delta isoform, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta, PI3Kdelta, PI3K-delta, PI3-kinase subunit delta, PI3-kinase p110 subunit delta, P110delta | Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Have a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Have important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '04 Diseases of the immune system', '12 Diseases of the respiratory system', '15 Diseases of the musculoskeletal system or connective tissue'] | 4 | Downloaded from PDB (6PYR) | 6PYR |
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Go to ligands | 35.7500 13.2800 32.4900 | |
| D0212 | Stress-activated protein kinase JNK1 | P45983 | MK08_HUMAN | Stress-activated protein kinase 1c, SAPK1c, PRKM8, Mitogen-activated protein kinase 8, MAPK 8, MAP kinase 8, JNK-46, C-Jun N-terminal kinase 1 | Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock. Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity. Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation. Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (3ELJ) | 3ELJ |
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Go to ligands | 19.3100 8.6100 31.8300 | |
| D0213 | DNA-binding factor KBF1 | P19838 | NFKB1_HUMAN | Nuclear factor of kappa light polypeptide gene enhancer in Bcells 1, Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1, Nuclear factor NFkappaB p50 subunit, Nuclear factor NFkappaB p105 subunit, Nuclear factor NF-kappa-B p105 subunit, EBP1, EBP-1, DNAbinding factor KBF1 | NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling, active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105. NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. | Factors and Regulators | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system'] | 3 | Downloaded from PDB (1SVC) | 1SVC |
|
Go to ligands | 32.6400 18.2200 37.0000 | |
| D0214 | Protein kinase C beta | P05771 | KPCB_HUMAN | Protein kinase C beta type, PRKCB1, PKCB, PKC-beta, PKC-B | Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. May participate in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '08 Diseases of the nervous system', '22 Injury, poisoning or certain other consequences of external causes'] | 3 | Downloaded from PDB (2I0E) | 2I0E |
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Go to ligands | 36.4500 55.4200 34.7100 | |
| D0215 | Matrix metalloproteinase-2 | P08253 | MMP2_HUMAN | TBE-1, Matrix metalloproteinase 2, CLG4A, 72 kDa type IV collagenase, 72 kDa gelatinase | As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14. Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. | Enzyme | Hydrolase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '13 Diseases of the digestive system', '14 Diseases of the skin'] | 3 | Downloaded from PDB (7XJO) | 7XJO |
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Go to ligands | 55.2700 -52.1400 19.9500 | |
| D0216 | Neutrophil elastase | P08246 | ELNE_HUMAN | PMN elastase, Medullasin, Human leukocyte elastase, HLE, Elastase-2, ELA2, Bone marrow serine protease | Inhibits C5a-dependent neutrophil enzyme release and chemotaxis. Modifies the functions of natural killer cells, monocytes and granulocytes. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['08 Diseases of the nervous system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue', '22 Injury, poisoning or certain other consequences of external causes'] | 7 | Downloaded from PDB (5ABW) | 5ABW |
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Go to ligands | 26.1300 -26.5800 3.0400 | |
| D0217 | Follicle-stimulating hormone receptor | P23945 | FSHR_HUMAN | LGR1, Follitropin receptor, FSH-R | G protein-coupled receptor for follitropin, the follicle-stimulating hormone. Through cAMP production activates the downstream PI3K-AKT and ERK1/ERK2 signaling pathways. | Receptor | - | Successful | ['16 Diseases of the genitourinary system'] | 1 | ['01 Certain infectious or parasitic diseases'] | 1 | Downloaded from PDB (8I2G) | 8I2G |
|
Go to ligands | 136.4200 142.7900 147.1200 | |
| D0218 | Bromodomain-containing protein 4 | O60885 | BRD4_HUMAN | Protein HUNK1, HUNK1 | Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure. During interphase, plays a key role in regulating the transcription of signal-inducible genes by associating with the P-TEFb complex and recruiting it to promoters. Also recruits P-TEFb complex to distal enhancers, so called anti-pause enhancers in collaboration with JMJD6. BRD4 and JMJD6 are required to form the transcriptionally active P-TEFb complex by displacing negative regulators such as HEXIM1 and 7SKsnRNA complex from P-TEFb, thereby transforming it into an active form that can then phosphorylate the C-terminal domain (CTD) of RNA polymerase II. Promotes phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II. According to a report, directly acts as an atypical protein kinase and mediates phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II, these data however need additional evidences in vivo. In addition to acetylated histones, also recognizes and binds acetylated RELA, leading to further recruitment of the P-TEFb complex and subsequent activation of NF-kappa-B. Also acts as a regulator of p53/TP53-mediated transcription: following phosphorylation by CK2, recruited to p53/TP53 specific target promoters. | Factors and Regulators | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '08 Diseases of the nervous system'] | 2 | Downloaded from PDB (6FO5) | 6FO5 |
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Go to ligands | 54.0800 4.6500 10.1700 | |
| D0219 | Histone deacetylase 1 | Q13547 | HDAC1_HUMAN | RPD3L1, HD1 | Gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation. Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). | Enzyme | Hydrolase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '03 Diseases of the blood or blood-forming organs', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '22 Injury, poisoning or certain other consequences of external causes'] | 6 | Downloaded from PDB (4BKX) | 4BKX |
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Go to ligands | -47.1700 17.0800 -8.2700 | |
| D0220 | Polo-like kinase 1 | P53350 | PLK1_HUMAN | Serine/threonine-protein kinase PLK1, Serine/threonine-protein kinase 13, Serine-threonine protein kinase 13, STPK13, Plk1, PLK-1, PLK, Mitoticserine-threonine kinase polo-like kinase 1 | Polo-like kinase proteins acts by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, PPP1R12A/MYPT1, PRC1, RACGAP1/CYK4, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU. Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL. NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins. Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1. Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2, creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains. Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation. Promotes the central spindle recruitment of ECT2. Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1. Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1. Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase. Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity. Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2. PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation. Required for kinetochore localization of BUB1B. Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2. Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function. Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome. Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53. Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA. Contributes to the regulation of AURKA function. Also required for recovery after DNA damage checkpoint and entry into mitosis. Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning. Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage. Phosphorylates CEP68 and is required for its degradation. Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope. Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock. Phosphorylates HSF1 also in the early mitotic period, this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression. Regulates mitotic progression by phosphorylating RIOK2. Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4X9R) | 4X9R |
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Go to ligands | -11.8400 21.0700 80.9700 | |
| D0221 | Phosphodiesterase 5A | O76074 | PDE5A_HUMAN | cGMP-specific 3',5'-cyclic phosphodiesterase, PDE5A, CGMP-binding cGMP-specific phosphodiesterase, CGB-PDE | Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP. Specifically regulates nitric-oxide-generated cGMP. | Enzyme | Hydrolase | Successful | ['04 Diseases of the immune system', '11 Diseases of the circulatory system', '17 Conditions related to sexual health', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 4 | ['02 Neoplasms', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system'] | 3 | Downloaded from PDB (2H44) | 2H44 |
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Go to ligands | 70.0400 26.7300 25.9900 | |
| D0222 | Orexin receptor type 2 | O43614 | OX2R_HUMAN | Ox2r, Ox2-R, Ox-2-R, Orexin-2 receptor, Hypocretin receptor type 2, HFGANP | Triggers an increase in cytoplasmic Ca(2+) levels in response to orexin-A binding. Nonselective, high-affinity receptor for both orexin-A and orexin-B neuropeptides. | Receptor | - | Successful | ['07 Sleep-wake disorders'] | 1 | ['06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders'] | 2 | Downloaded from PDB (7L1V) | 7L1V |
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Go to ligands | 122.2400 125.6000 159.8800 | |
| D0223 | Cathepsin L | P07711 | CATL1_HUMAN | Major excreted protein, MEP, Cathepsin L1, CTSL1 | Important for the overall degradation of proteins in lysosomes. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['03 Diseases of the blood or blood-forming organs'] | 1 | Downloaded from PDB (2XU3) | 2XU3 |
|
Go to ligands | 16.6700 4.2700 7.8000 | |
| D0224 | Survival motor neuron protein | Q16637 | SMN_HUMAN | SMNT, SMNC, SMN2, SMN, Gemin-1, Component of gems 1 | Thereby, plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus. Ensures the correct splicing of U12 intron-containing genes that may be important for normal motor and proprioceptive neurons development. Also required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs). The SMN complex plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. | Factors and Regulators | - | Successful | ['08 Diseases of the nervous system'] | 1 | ['No clinical molecule'] | 0 | Downloaded from PDB (7W2P) | 7W2P |
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Go to ligands | -6.3500 8.8600 1.5100 | |
| D0225 | Melanocortin receptor 4 | P32245 | MC4R_HUMAN | MC4-R | Plays a central role in energy homeostasis and somatic growth. This receptor is mediated by G proteins that stimulate adenylate cyclase (cAMP). Receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. | Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '13 Diseases of the digestive system', '17 Conditions related to sexual health'] | 3 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '14 Diseases of the skin', '17 Conditions related to sexual health', '20 Developmental anomalies'] | 6 | Downloaded from PDB (7PIU) | 7PIU |
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Go to ligands | 110.7100 109.7900 144.4500 | |
| D0226 | Leukocyte common antigen | P08575 | PTPRC_HUMAN | T200, Receptor-type tyrosine-protein phosphatase C, L-CA, CD45 antigen, CD45 | Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity. Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '22 Injury, poisoning or certain other consequences of external causes', '24 Factors influencing health status or contact with health services'] | 3 | Downloaded from PDB (1YGU) | 1YGU |
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Go to ligands | 15.9200 -7.1900 57.9800 | |
| D0227 | Matrix metalloproteinase-7 | P09237 | MMP7_HUMAN | Uterine metalloproteinase, Pump-1 protease, PUMP1, Matrin, Matrilysin, MPSL1 | Activates procollagenase. Degrades casein, gelatins of types I, III, IV, and V, and fibronectin. | Enzyme | Hydrolase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms'] | 1 | Downloaded from PDB (1MMQ) | 1MMQ |
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Go to ligands | 48.9200 -38.1100 53.9500 | |
| D0228 | Estradiol 17 beta-dehydrogenase 1 | P14061 | DHB1_HUMAN | Short chain dehydrogenase/reductase family 28C member 1, SDR28C1, Placental 17-beta-hydroxysteroid dehydrogenase, Estradiol 17-beta-dehydrogenase 1, EDHB17, EDH17B2, EDH17B1, E2DH, E17KSR, 20-alpha-HSD, 20 alpha-hydroxysteroid dehydrogenase, 17-beta-Hydroxysteroid dehydrogenase type 1, 17-beta-HSD 1 | Has 20-alpha-HSD activity. Uses preferentially NADH. Favors the reduction of estrogens and androgens. | Enzyme | Oxidoreductase | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases'] | 1 | Downloaded from PDB (1JTV) | 1JTV |
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Go to ligands | 10.4900 8.4800 -11.8400 | |
| D0229 | Glutamate receptor ionotropic kainate 1 | P39086 | GRIK1_HUMAN | Glutamate receptor 5, GluR5 kainate receptor, GluR5, GluR-5, GRIK1, Excitatory amino acid receptor 3, EAA3 | Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L- glutamate induces a conformation change, leading tothe opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus. | Receptor | - | Successful | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system'] | 2 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 3 | Downloaded from PDB (3FV1) | 3FV1 |
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Go to ligands | -7.0200 3.6700 -12.5600 | |
| D0230 | Cyclin-dependent kinase 9 | P50750 | CDK9_HUMAN | Tat-associated kinase complex catalytic subunit, TAK, Similar to cyclin-dependent kinase 9, Serine/threonine-protein kinase PITALRE, Cyclin-dependent protein kinase Cdk9, Cell division protein kinase 9, Cell division cycle 2-like protein kinase 4, CDC2L4, CDC2-related kinase, C-2K | Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR, and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e. g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3, integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein, the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation. Protein kinase involved in the regulation of transcription. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '13 Diseases of the digestive system'] | 2 | Downloaded from PDB (3BLR) | 3BLR |
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Go to ligands | 51.9400 -15.1200 -12.6400 | |
| D0231 | Neuronal acetylcholine receptor alpha-3/beta-4 | P32297+P30926 | ACHA3_HUMAN-ACHB4_HUMAN | Neuronal acetylcholine receptor | A type of nicotinic acetylcholine receptor, consisting of 3 and 4 subunits. | Receptor | - | Successful | ['21 Symptoms, signs or clinical findings, not elsewhere classified'] | 1 | ['06 Mental, behavioural or neurodevelopmental disorders', '14 Diseases of the skin'] | 2 | Downloaded from PDB (6PV7) | 6PV7 |
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Go to ligands | 144.7400 136.6700 181.7400 | |
| D0232 | Fms-like tyrosine kinase 3 | P36888 | FLT3_HUMAN | Stem cell tyrosine kinase 1, STK1, STK-1, Receptor-type tyrosine-protein kinase FLT3, Fetal liver kinase-2, FLT-3, FLK2, FLK-2, FL cytokine receptor, CD135 | Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways. | Enzyme | Transferase | Successful | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '12 Diseases of the respiratory system'] | 3 | ['02 Neoplasms', '08 Diseases of the nervous system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue', '20 Developmental anomalies', '21 Symptoms, signs or clinical findings, not elsewhere classified', '24 Factors influencing health status or contact with health services'] | 7 | Downloaded from PDB (6JQR) | 6JQR |
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Go to ligands | -26.3300 -8.8300 -29.4600 | |
| D0233 | Angiotensin II receptor type-1 | P30556 | AGTR1_HUMAN | Type-1 angiotensin II receptor, Angiotensin II type-1 receptor, Angiotensin II receptor 1, Angiotensin 1 receptor, AT2R1B, AT2R1, AT1BR, AT1AR, AT1, AGTR1B, AGTR1A | Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Receptor for angiotensin II. | Receptor | - | Successful | ['11 Diseases of the circulatory system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 2 | ['05 Endocrine, nutritional or metabolic diseases', '11 Diseases of the circulatory system'] | 2 | Downloaded from PDB (6OS2) | 6OS2 |
|
Go to ligands | -14.7100 -16.0500 -71.2800 | |
| D0234 | Serine/threonine-protein kinase mTOR | P42345 | MTOR_HUMAN | Target of rapamycin, TOR kinase, Rapamycin target protein 1, Rapamycin target protein, Rapamycin and FKBP12 target 1, RAPT1, RAFT1, Mechanistic target of rapamycin, Mammalian target of rapamycin, FRAP2, FRAP1, FRAP, FKBP12-rapamycin complex-associated protein, FKBP-rapamycin associated protein, FK506-binding protein 12-rapamycin complex-associated protein 1 | MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4. Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'. Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms. Plays an important regulatory role in the circadian clock function, regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks. Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. | Enzyme | Transferase | Successful | ['02 Neoplasms', '11 Diseases of the circulatory system', '22 Injury, poisoning or certain other consequences of external causes'] | 3 | ['02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 5 | Modelled with SWISS-MODEL (6ZWM.1.A) | Homology |
|
Go to ligands | 178.6800 232.6800 204.7200 | |
| D0235 | Tryptophan 2,3-dioxygenase | P48775 | T23O_HUMAN | Tryptophanase, Tryptophan pyrrolase, Tryptophan oxygenase, Tryptamin 2,3-dioxygenase, TRPO, TO | Catalyzes the oxidative cleavage of the indole moiety. Heme-dependent dioxygenase that catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L-tryptophan to N-formyl-L-kynurenine. | Enzyme | Oxidoreductase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6PYZ) | 6PYZ |
|
Go to ligands | 15.1600 -56.8400 -54.5200 | |
| D0236 | Janus kinase 2 | O60674 | JAK2_HUMAN | Tyrosine-protein kinase JAK2 | Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO), or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin. Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. | Enzyme | Transferase | Successful | ['02 Neoplasms', '03 Diseases of the blood or blood-forming organs', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 4 | ['02 Neoplasms', '04 Diseases of the immune system', '08 Diseases of the nervous system', '12 Diseases of the respiratory system', '14 Diseases of the skin'] | 5 | Downloaded from PDB (7LL4) | 7LL4 |
|
Go to ligands | 11.8100 -17.5100 6.0700 | |
| D0237 | Staphylococcus DNA gyrase A | P20831 | GYRA_STAAU | Stap-coc DNA gyrase subunit A | A type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to modulate DNA topology and maintain chromosomes in an underwound state. Negative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Also able to catalyze the interconversion of other topological isomers of dsDNA rings, including catenanes and knotted rings. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner. | Enzyme | Isomerase | Successful | ['01 Certain infectious or parasitic diseases'] | 1 | ['01 Certain infectious or parasitic diseases'] | 1 | Downloaded from PDB (7MVS) | 7MVS |
|
Go to ligands | -8.8100 -44.4300 -26.7500 | |
| D0238 | Protein kinase C delta | Q05655 | KPCD_HUMAN | nPKC-delta, Tyrosine-protein kinase PRKCD, SDK1, Protein kinase C delta type catalytic subunit, Protein kinase C delta type, PKC-delta | Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction. Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation. Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways. May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion, acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin. The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion. Phosphorylates ELAVL1 in response to angiotensin-2 treatment. Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['11 Diseases of the circulatory system'] | 1 | Modelled with SWISS-MODEL (3PFQ.1.A) | Homology |
|
Go to ligands | -48.9000 24.0800 -17.8900 | |
| D0239 | Quinone reductase 2 | P16083 | NQO2_HUMAN | Quinone oxidoreductase 2, Qui reductase 2, QR2, NRH:quinone oxidoreductase 2, NRH:qui oxidoreductase 2, NQO2, NAD(P)H qui oxidoreductase 2 | The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis. | Enzyme | Oxidoreductase | Successful | ['07 Sleep-wake disorders'] | 1 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4FGL) | 4FGL |
|
Go to ligands | 17.8500 9.8800 8.1100 | |
| D0240 | Carnitine O-palmitoyltransferase I | Q92523 | CPT1B_HUMAN | KIAA1670, Carnitine palmitoyltransferase I-like protein, Carnitine palmitoyltransferase I, Carnitine palmitoyltransferase 1B, Carnitine palmitoyl-transferase I, Carnitine o-palmitoyltransferase-1, Carnitine O-palmitoyltransferase I, muscle isoform, Carnitine O-palmitoyltransferase 1, muscle isoform, CPTI-M, CPTI-L, CPT1-M, CPT-1, CPT I, CPT | mitochondrial outer membrane, mitochondrion, carnitine O-palmitoyltransferase activity, carnitine metabolic process, carnitine shuttle, fatty acid beta-oxidation, long-chain fatty acid transport. | Enzyme | Transferase | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '11 Diseases of the circulatory system'] | 3 | ['No clinical molecule'] | 0 | Modelled with AlphaFold (AF-Q92523-F1-model_v4) | Ab initio |
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Go to ligands | -2.3300 -0.8500 5.7200 | |
| D0241 | FK506-binding protein 1A | P62942 | FKB1A_HUMAN | Rotamase, Peptidyl-prolyl cis-trans isomerase FKBP1A, PPIase FKBP1A, Immunophillin FKBP, Immunophilin FKBP12, FKBP12, FKBP1, FKBP-1A, FKBP-12, FK-binding protein 12, Calstabin-1, 12 kDa FKBP, 12 kDa FK506-binding protein | Recruits SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. | Enzyme | Isomerase | Successful | ['22 Injury, poisoning or certain other consequences of external causes'] | 1 | ['08 Diseases of the nervous system', '14 Diseases of the skin', '22 Injury, poisoning or certain other consequences of external causes'] | 3 | Downloaded from PDB (6YF3) | 6YF3 |
|
Go to ligands | -0.7400 -11.5600 21.2800 | |
| D0242 | Thromboxane A2 receptor | P21731 | TA2R_HUMAN | TXA2-R, TXA2 receptor, Prostanoid TP receptor | The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system. In the kidney, the binding of TXA2 to glomerular TP receptors causes intense vasoconstriction. Activates phospholipase C. Isoform 1 activates adenylyl cyclase. Isoform 2 inhibits adenylyl cyclase. Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation. | Receptor | - | Successful | ['11 Diseases of the circulatory system', '17 Conditions related to sexual health'] | 2 | ['02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system'] | 5 | Downloaded from PDB (6IIU) | 6IIU |
|
Go to ligands | 25.2400 163.8200 147.6500 | |
| D0243 | Liver carboxylesterase | P23141 | EST1_HUMAN | Serine esterase 1, Monocyte/macrophage serine esterase, Human carboxylesterase 1, HMSE, HCE1, CES1, Brain carboxylesterase hBr1, Acyl coenzyme A:cholesterol acyltransferase | Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl coa ester. | Enzyme | Hydrolase | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '11 Diseases of the circulatory system'] | 3 | Downloaded from PDB (5A7F) | 5A7F |
|
Go to ligands | 26.4200 -15.5700 27.0200 | |
| D0244 | Glutamate receptor ionotropic NMDA 2B | Q13224 | NMDE2_HUMAN | NR3, NR2B, NMDA receptor subunit 2B, NMDA receptor NR2B, NMDA NR2B receptor, N-methylD-aspartate receptor subtype 2B, N-methyl-D-aspartate receptor subunit 3, N-methyl D-aspartate receptor subtype 2B, HNR3, Glutamate receptor ionotropic, NMDA 2B, Glutamate receptor NR2B subunit, Glutamate [NMDA] receptor subunit epsilon-2, GluN2B | Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death. Contributes to neural pattern formation in the developing brain. Plays a role in long-term depression (LTD) of hippocampus membrane currents and in synaptic plasticity. Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. | Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 3 | Downloaded from PDB (5EWM) | 5EWM |
|
Go to ligands | 28.6200 -2.0000 -36.3600 | |
| D0245 | Coagulation factor XI | P03951 | FA11_HUMAN | Plasma thromboplastin antecedent, PTA, FXI | Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['08 Diseases of the nervous system', '11 Diseases of the circulatory system', '13 Diseases of the digestive system', '16 Diseases of the genitourinary system'] | 4 | Downloaded from PDB (6TS4) | 6TS4 |
|
Go to ligands | 29.5900 3.7800 -3.3400 | |
| D0246 | Cannabinoid receptor 1 | P21554 | CNR1_HUMAN | Cannabinoid CB1 receptor, CNR, CB-R, CANN6 | Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP. In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses. At high doses, CNR1 signal transduction involves G-protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2. In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression. In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake. In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission. Also reduces excitatory synaptic transmission. In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+) channels in a constitutive, as well as agonist-dependent manner. In cerebral vascular smooth muscle cells, cannabinoid-induced inhibition of voltage-gated Ca(2+) channels leads to vasodilation and decreased vascular tone. Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia. In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes. In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism. In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism. In response to cannabinoid anandamide, elicits a proinflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion. In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta-cells. G-protein coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta(9)-tetrahydrocannabinol (THC). | Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders'] | 3 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '16 Diseases of the genitourinary system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 5 | Downloaded from PDB (5XRA) | 5XRA |
|
Go to ligands | -42.9400 -165.1600 306.2700 | |
| D0247 | Glycogen synthase kinase-3 alpha | P49840 | GSK3A_HUMAN | Serine/threonineprotein kinase GSK3A, Serine/threonine-protein kinase GSK3A, Glycogen synthase kinase3 alpha, Glycogen synthase kinase 3, GSK3 alpha, GSK-3 alpha, GSK-3 | Requires primed phosphorylation of the majority of its substrates. Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. Regulates glycogen metabolism in liver, but not in muscle. May also mediate the development of insulin resistance by regulating activation of transcription factors. In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin. Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease. May be involved in the regulation of replication in pancreatic beta-cells. Is necessary for the establishment of neuronal polarity and axon outgrowth. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer. Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1. | Enzyme | Transferase | Successful | ['08 Diseases of the nervous system'] | 1 | ['02 Neoplasms', '06 Mental, behavioural or neurodevelopmental disorders', '20 Developmental anomalies'] | 3 | Modelled with SWISS-MODEL (6AE3.1.A) | Homology |
|
Go to ligands | 29.1200 5.1900 -10.9500 | |
| D0248 | Glutaminyl cyclase | Q16769 | QPCT_HUMAN | sQC, QPCT, QC, Glutamyl cyclase, GlutaminyltRNA cyclotransferase, Glutaminylpeptide cyclotransferase, EC | Responsible for the biosynthesis of pyroglutamyl peptides. Has a bias against acidic and tryptophan residues adjacent to the N-terminal glutaminyl residue and a lack of importance of chain length after the second residue. Also catalyzes N-terminal pyroglutamate formation. In vitro, catalyzes pyroglutamate formation of N-terminally truncated form of APP amyloid-beta peptides [Glu-3]-beta-amyloid. May be involved in the N-terminal pyroglutamate formation of several amyloid-related plaque-forming peptides. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['06 Mental, behavioural or neurodevelopmental disorders'] | 1 | Downloaded from PDB (2AFX) | 2AFX |
|
Go to ligands | -16.5300 1.8600 22.3700 | |
| D0249 | M-phase inducer phosphatase 2 | P30305 | MPIP2_HUMAN | Dual specificity phosphatase Cdc25B, Cdc25B phosphatase, CDC25HU2 | Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Directly dephosphorylates CDK1 and stimulates its kinase activity. The three isoforms seem to have a different level of activity. Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4WH9) | 4WH9 |
|
Go to ligands | 13.3200 -8.6800 -4.0900 | |
| D0250 | Matrix metalloproteinase-12 | P39900 | MMP12_HUMAN | Macrophage metalloelastase, Macrophage elastase, MME, ME, HME | Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3. May be involved in tissue injury and remodeling. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '12 Diseases of the respiratory system'] | 2 | Downloaded from PDB (6EKN) | 6EKN |
|
Go to ligands | 3.7900 -13.0100 9.8700 | |
| D0251 | Adenosine A2a receptor | P29274 | AA2AR_HUMAN | Adenosine receptor A2a, ADORA2, A2a Adenosine receptor, A(2A) adenosine receptor | The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Receptor for adenosine. | Receptor | - | Successful | ['08 Diseases of the nervous system', '11 Diseases of the circulatory system'] | 2 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '09 Diseases of the visual system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system'] | 7 | Downloaded from PDB (3VG9) | 3VG9 |
|
Go to ligands | -73.6000 -12.2200 -45.9800 | |
| D0252 | Bacterial Botulinum toxin A | P0DPI0 | BXA1_CLOBO | botA | Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the 197-Gln-|-Arg- 198 bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '08 Diseases of the nervous system', '14 Diseases of the skin'] | 3 | Downloaded from PDB (6XCF) | 6XCF |
|
Go to ligands | 2.2300 -10.8300 18.9700 | |
| D0253 | Histamine H1 receptor | P35367 | HRH1_HUMAN | HH1R, H1R | In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system. | Receptor | - | Successful | ['04 Diseases of the immune system', '06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '08 Diseases of the nervous system', '09 Diseases of the visual system', '10 Diseases of the ear or mastoid process', '12 Diseases of the respiratory system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue', '21 Symptoms, signs or clinical findings, not elsewhere classified', '26 Supplementary Chapter Traditional Medicine Conditions'] | 11 | ['05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '12 Diseases of the respiratory system'] | 4 | Downloaded from PDB (7DFL) | 7DFL |
|
Go to ligands | 131.5700 133.1700 158.2200 | |
| D0254 | Aurora kinase B | Q96GD4 | AURKB_HUMAN | Serine/threonine-protein kinase aurora-B, Serine/threonine-protein kinase 5, Serine/threonine-protein kinase 12, Serine/threonine protein kinase 12, STK5, STK12, Aurora/IPL1-related kinase 2, Aurora-related kinase 2, Aurora-B, Aurora-2 kinase, Aurora-2, Aurora- and Ipl1-like midbody-associated protein 1, Aurora 1, ARK2, ARK-2, AIRK2, AIM1, AIM-1, AIK | The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis. Required for central/midzone spindle assembly and cleavage furrow formation. Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: phosphorylates CHMP4C, leading to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis. AURKB phosphorylates the CPC complex subunits BIRC5/survivin, CDCA8/borealin and INCENP. Phosphorylation of INCENP leads to increased AURKB activity. Other known AURKB substrates involved in centromeric functions and mitosis are CENPA, DES/desmin, GPAF, KIF2C, NSUN2, RACGAP1, SEPT1, VIM/vimentin, HASPIN, and histone H3. A positive feedback loop involving HASPIN and AURKB contributes to localization of CPC to centromeres. Phosphorylation of VIM controls vimentin filament segregation in cytokinetic process, whereas histone H3 is phosphorylated at 'Ser-10' and 'Ser-28' during mitosis (H3S10ph and H3S28ph, respectively). A positive feedback between HASPIN and AURKB contributes to CPC localization. AURKB is also required for kinetochore localization of BUB1 and SGO1. Phosphorylation of p53/TP53 negatively regulates its transcriptional activity. Key regulator of active promoters in resting B- and T-lymphocytes: acts by mediating phosphorylation of H3S28ph at active promoters in resting B-cells, inhibiting RNF2/RING1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes. Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases'] | 2 | Downloaded from PDB (4AF3) | 4AF3 |
|
Go to ligands | 17.6100 -21.5500 -7.9700 | |
| D0255 | 5-HT 1A receptor | P08908 | 5HT1A_HUMAN | Serotonin receptor 1A, G-21, ADRBRL1, ADRB2RL1, 5-hydroxytryptamine receptor 1A, 5-HT1A receptor, 5-HT1A, 5-HT-1A | Functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli. G-protein coupled receptor for 5-hydroxytryptamine (serotonin). | Receptor | - | Successful | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '11 Diseases of the circulatory system'] | 3 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue', '17 Conditions related to sexual health', '20 Developmental anomalies', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 11 | Downloaded from PDB (7E2Y) | 7E2Y |
|
Go to ligands | 102.9800 115.3100 107.2300 | |
| D0256 | Bacterial Fatty acid synthetase I | P9WGR1 | INHA_MYCTU | Enoyl-[acyl-carrier-protein] reductase [NADH], Bacterial InhA | Involved in the resistance against the antituberculosis drugs isoniazid and ethionamide. | Enzyme | Oxidoreductase | Successful | ['01 Certain infectious or parasitic diseases'] | 1 | ['01 Certain infectious or parasitic diseases'] | 1 | Downloaded from PDB (4OHU) | 4OHU |
|
Go to ligands | 2.5800 -14.3600 49.6900 | |
| D0257 | Thyroid hormone receptor alpha | P10827 | THA_HUMAN | V-erbA-related protein 7, THRA2, THRA1, Nuclear receptor subfamily 1 group A member 1, NR1A1, ERBA1, EAR7, EAR-7, C-erbA-alpha, C-erbA-1 | High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription. | Nuclear Hormone Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['11 Diseases of the circulatory system', '14 Diseases of the skin'] | 2 | Downloaded from PDB (3HZF) | 3HZF |
|
Go to ligands | 21.0500 8.8900 6.2600 | |
| D0258 | Muscarinic acetylcholine receptor M5 | P08912 | ACM5_HUMAN | CHRM5 | After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. | Receptor | - | Successful | ['01 Certain infectious or parasitic diseases', '08 Diseases of the nervous system', '09 Diseases of the visual system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '16 Diseases of the genitourinary system', '21 Symptoms, signs or clinical findings, not elsewhere classified', '22 Injury, poisoning or certain other consequences of external causes', '24 Factors influencing health status or contact with health services'] | 10 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6OL9) | 6OL9 |
|
Go to ligands | 35.0300 23.8500 -41.7800 | |
| D0259 | PI3-kinase alpha | P42336 | PK3CA_HUMAN | p110alpha, Serine/threonine protein kinase PIK3CA, PtdIns3kinase subunit p110alpha, PtdIns3kinase subunit alpha, PtdIns-3-kinase subunit p110-alpha, PtdIns-3-kinase subunit alpha, Phosphoinositide3kinase catalytic alpha polypeptide, Phosphoinositide-3-kinase catalytic alpha polypeptide, Phosphatidylinositol 4,5bisphosphate 3kinase catalytic subunit alpha isoform, Phosphatidylinositol 4,5bisphosphate 3kinase 110 kDa catalytic subunit alpha, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha, PI3kinase subunit alpha, PI3Kalpha, PI3K-alpha, PI3-kinase subunit alpha | Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Also has serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS. Plays a role in the positive regulation of phagocytosis and pinocytosis. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms'] | 1 | Downloaded from PDB (8EXL) | 8EXL |
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Go to ligands | -15.5600 13.0100 27.6100 | |
| D0260 | GABA A receptor beta-2 | P47870 | GBRB2_HUMAN | GABRB2, GABA(A) receptor subunit beta-2 | Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital, these are bound at a separate allosteric effector binding site. Functions as ligand- gated chloride channel. | Receptor | - | Successful | ['06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 3 | ['08 Diseases of the nervous system', '13 Diseases of the digestive system'] | 2 | Downloaded from PDB (6X3T) | 6X3T |
|
Go to ligands | 111.5200 142.5200 143.9300 | |
| D0261 | Toll-like receptor 8 | Q9NR97 | TLR8_HUMAN | UNQ249/PRO286, CD288 antigen, CD288 | Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '04 Diseases of the immune system', '12 Diseases of the respiratory system', '14 Diseases of the skin'] | 5 | Downloaded from PDB (3WN4) | 3WN4 |
|
Go to ligands | 9.4400 20.2800 30.6200 | |
| D0262 | Estrogen receptor beta | Q92731 | ESR2_HUMAN | Oestrogen receptor beta, Nuclear receptor subfamily 3 group A member 2, NR3A2, Erbeta, ESTRB, ER-beta, Beta-1 | Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual. Nuclear hormone receptor. | Nuclear Hormone Receptor | - | Successful | ['02 Neoplasms', '05 Endocrine. Nutritional or metabolic diseases', '12 Diseases of the respiratory system', '16 Diseases of the genitourinary system'] | 4 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '13 Diseases of the digestive system', '16 Diseases of the genitourinary system'] | 6 | Downloaded from PDB (1QKM) | 1QKM |
|
Go to ligands | 22.9900 8.4600 113.5400 | |
| D0263 | Urotensin II receptor | Q9UKP6 | UR2R_HUMAN | Urotensin-II receptor GPR14, UTS2R, UR-II-R, G protein coupled receptor 14 | High affinity receptor for urotensin-2 and urotensin-2B. The activity of this receptor is mediated by a G-protein that activate a phosphatidylinositol-calcium second messenger system. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['12 Diseases of the respiratory system'] | 1 | Modelled with AlphaFold (AF-Q9UKP6-F1-model_v4) | Ab initio |
|
Go to ligands | -7.7800 -2.1200 0.4500 | |
| D0264 | Acetyl-CoA carboxylase 2 | O00763 | ACACB_HUMAN | Acetyl-Coenzyme A carboxylase beta, Acetyl CoA carboxylase beta, ACCbeta, ACC2, ACC-beta, ACACB | Catalyzes the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in inhibition of fatty acid and glucose oxidation and enhancement of fat storage. May play a role in regulation of mitochondrial fatty acid oxidation through malonyl- CoA-dependent inhibition of carnitine palmitoyltransferase 1. | Enzyme | Ligase | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['No clinical molecule'] | 0 | Downloaded from PDB (3GID) | 3GID |
|
Go to ligands | -50.9100 -42.8100 -8.6700 | |
| D0265 | Vascular endothelial growth factor receptor 2 | P35968 | VGFR2_HUMAN | VEGFR2, VEGFR-2, VEGF-2 receptor, Protein-tyrosine kinase receptor flk-1, Kinase insert domain receptor, Fetal liver kinase 1, FLK1, FLK-1, CD309 | Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC. Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. | Enzyme | Transferase | Successful | ['02 Neoplasms', '03 Diseases of the blood or blood-forming organs'] | 2 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 5 | Downloaded from PDB (3VHE) | 3VHE |
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Go to ligands | -26.4000 -0.4900 -9.3100 | |
| D0266 | Tyrosine-protein phosphatase non-receptor type 2 | P17706 | PTN2_HUMAN | T-cell protein-tyrosine phosphatase, TCPTP | Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3 and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the development of the immune system. Functions in T-cell receptor signaling through dephosphorylation of FYN and LCK to control T-cells differentiation and activation. Dephosphorylates CSF1R, negatively regulating its downstream signaling and macrophage differentiation. Negatively regulates cytokine (IL2/interleukin-2 and interferon)-mediated signaling through dephosphorylation of the cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that propagate signaling downstream of the cytokine receptors. Also regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine signaling through dephosphorylation of STAT3 and STAT6 respectively. In addition to the immune system, it is involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth. Activated by the integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates EGF signaling. Dephosphorylates PDGFRB and negatively regulates platelet-derived growth factor receptor-beta signaling pathway and therefore cell proliferation. Negatively regulates tumor necrosis factor-mediated signaling downstream via MAPK through SRC dephosphorylation. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of the hepatocyte growth factor receptor MET. Plays also an important role in glucose homeostasis. For instance, negatively regulates the insulin receptor signaling pathway through the dephosphorylation of INSR and control gluconeogenesis and liver glucose production through negative regulation of the IL6 signaling pathways. May also bind DNA. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (7F5O) | 7F5O |
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Go to ligands | -6.1000 8.8700 -1.6500 | |
| D0267 | Tyrosine-protein kinase UFO | P30530 | UFO_HUMAN | UFO, Tyrosine-protein kinase receptor UFO, AXL oncogene | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, ALX binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3, but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5U6B) | 5U6B |
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Go to ligands | 26.3800 -20.9200 -24.8500 | |
| D0268 | Angiotensin-converting enzyme | P12821 | ACE_HUMAN | Kininase II, Dipeptidyl carboxypeptidase I, DCP1, DCP, CD143 antigen, CD143, ACE | Able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. | Enzyme | Hydrolase | Successful | ['11 Diseases of the circulatory system'] | 1 | ['11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system'] | 3 | Downloaded from PDB (6F9T) | 6F9T |
|
Go to ligands | -15.0300 -5.7900 20.5500 | |
| D0269 | Ephrin type-B receptor 4 | P54760 | EPHB4_HUMAN | Tyrosine-protein kinase TYRO11, TYRO11, MYK1, Hepatoma transmembrane kinase, HTK | Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 it is involved in the regulation of cell adhesion and migration, and plays a central role in heart morphogenesis, angiogenesis and blood vessel remodeling and permeability. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '16 Diseases of the genitourinary system'] | 2 | Downloaded from PDB (6FNM) | 6FNM |
|
Go to ligands | 34.7600 3.5400 71.5200 | |
| D0270 | Plasma kallikrein | P03952 | KLKB1_HUMAN | Plasma prekallikrein, Plasma kallikrein light chain, Plasma kallikrein heavy chain, PKK, Kininogenin, KLK3, Fletcher factor | It activates, in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin. The enzyme cleaves Lys-Arg and Arg-Ser bonds. | Enzyme | Hydrolase | Successful | ['04 Diseases of the immune system', '09 Diseases of the visual system'] | 2 | ['09 Diseases of the visual system'] | 1 | Downloaded from PDB (6O1S) | 6O1S |
|
Go to ligands | -11.0800 -3.6900 15.0500 | |
| D0271 | Cyclin-dependent kinase 1 | P06493 | CDK1_HUMAN | P34CDC2, P34 protein kinase, CDKN1, CDC28A, CDC2 | Required in higher cells for entry into S-phase and mitosis. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SAMHD1, SIRT2 and RUNX2. CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs. Essential for early stages of embryonic development. During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation. Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis. Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression. In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis. NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis. The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis. In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration. CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis. Regulates the amplitude of the cyclic expression of the core clock gene ARNTL/BMAL1 by phosphorylating its transcriptional repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)-mediated ubiquitination and proteasomal degradation of NR1D1. Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset, promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4Y72) | 4Y72 |
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Go to ligands | 27.6200 -71.4300 186.0400 | |
| D0272 | CREB-binding protein | Q92793 | CBP_HUMAN | CREBbinding protein, CBP | Acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers. Acetylates PCNA, acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway. Acetylates histones, giving a specific tag for transcriptional activation. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '04 Diseases of the immune system'] | 2 | Downloaded from PDB (5I86) | 5I86 |
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Go to ligands | -58.2800 -14.8100 16.3800 | |
| D0273 | Monoamine oxidase type B | P27338 | AOFB_HUMAN | MAO-B, Amine oxidase [flavin-containing] B | Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine. | Enzyme | Oxidoreductase | Successful | ['01 Certain infectious or parasitic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '11 Diseases of the circulatory system'] | 4 | ['08 Diseases of the nervous system', '14 Diseases of the skin'] | 2 | Downloaded from PDB (2XCG) | 2XCG |
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Go to ligands | 50.3900 161.4300 30.4600 | |
| D0274 | TGF-beta receptor type II | P37173 | TGFR2_HUMAN | Transforminggrowth factor-beta receptor type II, Transforming growth factor-beta receptor type II, TbetaR-II, TGFR-2, TGF-beta type II receptor, TGF-beta receptor type-2 | Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4XJJ) | 4XJJ |
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Go to ligands | 36.3600 63.2900 5.2100 | |
| D0275 | Sphingosine-1-phosphate receptor 5 | Q9H228 | S1PR5_HUMAN | Sphingosine 1-phosphate receptor Edg-8, S1PR5, S1P5, S1P receptor Edg-8, S1P receptor 5, Endothelial differentiation G-protein-coupled receptor 8 | Receptor for the lysosphingolipid sphingosine 1- phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. Is coupled to both the G(i/0)alpha and G(12) subclass of heteromeric G-proteins. May play a regulatory role in the transformation of radial glial cells into astrocytes and may affect proliferative activity of these cells. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['08 Diseases of the nervous system'] | 1 | Downloaded from PDB (7YXA) | 7YXA |
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Go to ligands | 12.3700 17.4200 12.0100 | |
| D0276 | Transient receptor potential cation channel V1 | Q8NER1 | TRPV1_HUMAN | Vanilloid receptor 1, VR1, TrpV1, Transient receptor potential cation channel subfamily V member 1, Osm-9-like TRP channel 1, OTRPC1, Capsaicin receptor | Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis. | Receptor | - | Successful | ['08 Diseases of the nervous system'] | 1 | ['08 Diseases of the nervous system', '12 Diseases of the respiratory system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system', '20 Developmental anomalies', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 7 | Downloaded from PDB (8GFA) | 8GFA |
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Go to ligands | 107.9100 79.3500 90.9100 | |
| D0277 | Serine/threonine-protein kinase pim-1 | P11309 | PIM1_HUMAN | Pim-1 proto-oncogene, serine/threonine kinase, PIM | Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis. Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (3R04) | 3R04 |
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Go to ligands | 24.3700 -35.5500 -0.0500 | |
| D0278 | 5-HT 2C receptor | P28335 | 5HT2C_HUMAN | Serotonin receptor 2C, HTR1C, 5HT-1C, 5-hydroxytryptamine receptor 2C, 5-hydroxytryptamine receptor 1C, 5-HTR2C, 5-HT2C receptor, 5-HT2C, 5-HT1C, 5-HT-2C, 5-HT-1C | Functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis. G-protein coupled receptor for 5-hydroxytryptamine (serotonin). | Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 4 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '08 Diseases of the nervous system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 6 | Downloaded from PDB (6BQH) | 6BQH |
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Go to ligands | 39.0200 31.4600 55.8000 | |
| D0279 | Monoamine oxidase type A | P21397 | AOFA_HUMAN | Monoamine oxidase A, Amine oxidase [flavin-containing] A | MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine. Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. | Enzyme | Oxidoreductase | Successful | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system'] | 2 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '14 Diseases of the skin'] | 3 | Downloaded from PDB (2Z5X) | 2Z5X |
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Go to ligands | 41.5500 26.0100 -15.4200 | |
| D0280 | Transformation-sensitive protein p120 | O75762 | TRPA1_HUMAN | TRPA1, Ankyrin-like with transmembrane domains protein 1, ANKTM1 | Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function. Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes. Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)- tetrahydrocannabinol (THC), the psychoactive component of marijuana. Not involved in menthol sensation. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system. | Receptor | - | Successful | ['12 Diseases of the respiratory system'] | 1 | ['08 Diseases of the nervous system'] | 1 | Downloaded from PDB (6PQO) | 6PQO |
|
Go to ligands | 124.2100 -105.3600 151.9300 | |
| D0281 | Histone deacetylase 2 | Q92769 | HDAC2_HUMAN | HD2 | Gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR. Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation. Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A. Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (7KBG) | 7KBG |
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Go to ligands | 89.9900 45.8800 -34.0200 | |
| D0282 | Steroid 11-beta-hydroxylase | P15538 | C11B1_HUMAN | S11BH, P450C11, P-450c11, CYPXIB1, CYP11B1 | Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB. | Enzyme | Oxidoreductase | Successful | ['02 Neoplasms', '05 Endocrine. Nutritional or metabolic diseases'] | 2 | ['No clinical molecule'] | 0 | Downloaded from PDB (6M7X) | 6M7X |
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Go to ligands | 31.6200 -0.7200 11.0800 | |
| D0283 | Coagulation factor Xa | P00742 | FA10_HUMAN | Fxa, Factor Xa, F10, Activated coagulation factor X | Factor Xa is avitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting. | Enzyme | Hydrolase | Successful | ['03 Diseases of the blood or blood-forming organs', '11 Diseases of the circulatory system', '13 Diseases of the digestive system'] | 3 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '16 Diseases of the genitourinary system'] | 3 | Downloaded from PDB (2JKH) | 2JKH |
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Go to ligands | -1.0200 6.7700 25.8700 | |
| D0284 | Casein kinase II alpha | P68400 | CSK21_HUMAN | Protein kinase CK2, Casein kinase II subunit alpha, CK2A1, CK II alpha, CK II | Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation. Plays an important role in the circadian clock function by phosphorylating ARNTL/BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry. Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue. Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms'] | 2 | Downloaded from PDB (8AEC) | 8AEC |
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Go to ligands | -105.3800 -176.8400 314.2900 | |
| D0285 | BDNF/NT-3 growth factors receptor | Q16620 | NTRK2_HUMAN | Tropomyosin-related kinase B, TrkB tyrosine kinase, Trk-B, TRKB, Neurotrophic tyrosine kinase receptor type 2, GP145-TrkB | Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2. Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia. Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '08 Diseases of the nervous system'] | 2 | Downloaded from PDB (4AT5) | 4AT5 |
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Go to ligands | -14.6800 27.8800 -17.5400 | |
| D0286 | Insulin receptor | P06213 | INSR_HUMAN | IR, CD220 antigen, CD220 | Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD, regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. | Enzyme | Transferase | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '13 Diseases of the digestive system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 6 | Downloaded from PDB (5HHW) | 5HHW |
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Go to ligands | -9.9600 -23.2700 15.4000 | |
| D0287 | Cyclin-dependent kinase 4 | P11802 | CDK4_HUMAN | PSK-J3, Cell division protein kinase 4 | Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. | Enzyme | Transferase | Successful | ['02 Neoplasms', '14 Diseases of the skin'] | 2 | ['02 Neoplasms'] | 1 | Downloaded from PDB (7SJ3) | 7SJ3 |
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Go to ligands | 16.1900 -37.1800 10.4700 | |
| D0288 | Proto-oncogene c-Src | P12931 | SRC_HUMAN | pp60c-src, Tyrosine kinase (pp60(src)), Src tyrosine kinase, SRC1, Proto-oncogene tyrosine-protein kinase Src, Pp60(src), P60-Src, C-src TK, C-Src | Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1. Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors. Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation. Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase. Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731'. Enhances DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr-128'. Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity. Involved in anchorage-independent cell growth. Required for podosome formation. Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. | Enzyme | Transferase | Successful | ['02 Neoplasms', '08 Diseases of the nervous system'] | 2 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '14 Diseases of the skin'] | 6 | Downloaded from PDB (1O43) | 1O43 |
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Go to ligands | 13.6500 19.9900 19.2900 | |
| D0289 | Geranyltranstransferase | P14324 | FPPS_HUMAN | KIAA1293, Geranylgeranyl pyrophosphate synthase, Geranylgeranyl diphosphate synthase, GGPS1, GGPPSase, GGPP synthase, Farnesyltranstransferase, Farnesyl pyrophosphate synthase, Farnesyl diphosphate synthase, FPS protein, FPP synthase, Dimethylallyltranstransferase, (2E,6E)-farnesyl diphosphate synthase | FPP also serves as substrate for protein farnesylation and geranylgeranylation. Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate. Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. | Enzyme | Transferase | Successful | ['05 Endocrine. Nutritional or metabolic diseases', '15 Diseases of the musculoskeletal system or connective tissue'] | 2 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '08 Diseases of the nervous system'] | 3 | Downloaded from PDB (5CG5) | 5CG5 |
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Go to ligands | 16.1100 -32.8800 -8.2500 | |
| D0290 | Peroxisome proliferator-activated receptor alpha | Q07869 | PPARA_HUMAN | Peroxisome proliferater-activated receptor alpha, PPARalpha, PPAR-alpha, PPAR, Nuclear receptor subfamily 1 group C member 1, NR1C1 | Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2. Ligand-activated transcription factor. | Nuclear Hormone Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '11 Diseases of the circulatory system', '13 Diseases of the digestive system', '15 Diseases of the musculoskeletal system or connective tissue'] | 5 | Downloaded from PDB (1i7g) | 1i7g |
|
Go to ligands | 37.7900 35.5900 40.2600 | |
| D0291 | Alkaline phosphatase tissue-nonspecific | P05186 | PPBT_HUMAN | TNSALP, Liver/bone/kidney isozyme, Alkaline phosphatase, tissue-nonspecific isozyme, Alkaline phosphatase liver/bone/kidney isozyme, AP-TNAP | This isozyme plays a key role in skeletal mineralization by regulating levels of diphosphate (PPi). | Enzyme | Hydrolase | Successful | ['01 Certain infectious or parasitic diseases', '08 Diseases of the nervous system'] | 2 | ['05 Endocrine, nutritional or metabolic diseases'] | 1 | Modelled with SWISS-MODEL (4KJD.1.A) | Homology |
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Go to ligands | -26.5000 -8.3900 -19.4400 | |
| D0292 | Substance-K receptor | P21452 | NK2R_HUMAN | Tachykinin receptor 2, Tachykinin neurokinin 2 receptor, TACR2, SKR, Neurokinin A receptor, NK-2R, NK-2 receptor | This is a receptor for the tachykinin neuropeptide substance K (neurokinin A). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance K > neuromedin-K > substance P. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['13 Diseases of the digestive system', '14 Diseases of the skin'] | 2 | Modelled with SWISS-MODEL (7MRG.1.B) | Homology |
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Go to ligands | 123.6100 117.1000 88.8800 | |
| D0293 | Adenosine A2b receptor | P29275 | AA2BR_HUMAN | Adenosine receptor A2b, A2b Adenosine receptor | The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Receptor for adenosine. | Receptor | - | Successful | ['01 Certain infectious or parasitic diseases', '11 Diseases of the circulatory system'] | 2 | ['02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 5 | Downloaded from PDB (8HDO) | 8HDO |
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Go to ligands | 137.6200 127.1100 106.7900 | |
| D0294 | Amyloid beta A4 protein | P05067 | A4_HUMAN | Protease nexin-II, PreA4, PN-II, Cerebral vascular amyloid peptide, CVAP, Amyloid-beta precursor protein, Amyloid-beta A4 protein, Alzheimer disease amyloid protein, APPI, APP, AD1, ABPP, A4 | Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1. | Other | - | Successful | ['08 Diseases of the nervous system'] | 1 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '09 Diseases of the visual system', '14 Diseases of the skin'] | 4 | Modelled with AlphaFold (AF-P05067-F1-model_v4) | Ab initio |
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Go to ligands | -19.4300 -1.2900 -7.3900 | |
| D0295 | TGF-beta receptor type I | P36897 | TGFR1_HUMAN | Type I TGFbeta receptor kinase, Transforming growth factor-beta receptor type I, TbetaRI, TbetaR-I, TGFR-1, TGF-beta type I receptor, TGF-beta receptor type-1, Serine/threonine-protein kinase receptor R4, SKR4, Activin receptor-like kinase 5, Activin A receptor type II-like protein kinase of 53kD, ALK5, ALK-5 | Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation. Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '04 Diseases of the immune system', '11 Diseases of the circulatory system'] | 3 | Downloaded from PDB (4X2F) | 4X2F |
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Go to ligands | 16.5500 70.4700 4.8600 | |
| D0296 | G-protein coupled receptor 55 | Q9Y2T6 | GPR55_HUMAN | LPIR1 | Receptor for L-alpha-lysophosphatidylinositol (LPI). LPI induces Ca(2+) release from intracellular stores via the heterotrimeric G protein GNA13 and RHOA. Putative cannabinoid receptor. May play a role in bone physiology by regulating osteoclast number and function. May be involved in hyperalgesia associated with inflammatory and neuropathic pain. | Receptor | - | Successful | ['06 Mental, behavioural or neurodevelopmental disorders'] | 1 | ['20 Developmental anomalies'] | 1 | Modelled with SWISS-MODEL (7F2O.1.C) | Homology |
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Go to ligands | 116.4200 118.7400 85.1900 | |
| D0297 | Prolyl endopeptidase FAP | Q12884 | SEPR_HUMAN | Integral membrane serine protease, Fibroblast activation protein alpha, FAP, Antiplasmin-cleaving enzyme, APCE, 170-kDa melanoma membrane-bound gelatinase | Cell surface glycoprotein serine protease that participatesin extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammation and tumor growth. Both plasma membrane and soluble formsexhibit post-proline cleaving endopeptidase activity, with a marked preference for Ala/Ser-Gly-Pro-Ser/Asn/Ala consensus sequences, on substrate such as alpha-2-antiplasmin SERPINF2 and SPRY2 (PubMed:14751930, PubMed:16223769, PubMed:16480718, PubMed:16410248, PubMed:17381073, PubMed:18095711, PubMed:21288888, PubMed:24371721). Degrade also gelatin, heat-denatured type I collagen, but not native collagen type I and IV, vibronectin, tenascin, laminin, fibronectin, fibrin or casein (PubMed:9065413, PubMed:2172980, PubMed:7923219, PubMed:10347120, PubMed:10455171, PubMed:12376466, PubMed:16223769, PubMed:16651416, PubMed:18095711). Have also dipeptidyl peptidase activity, exhibiting the ability to hydrolyze the prolyl bond two residues from the N-terminus of synthetic dipeptide substrates provided that the penultimate residue is proline, with a preference for Ala-Pro, Ile-Pro, Gly-Pro, Arg-Pro and Pro-Pro (PubMed:10347120, PubMed:10593948, PubMed:16175601, PubMed:16223769, PubMed:16651416, PubMed:16410248, PubMed:17381073, PubMed:21314817, PubMed:24371721, PubMed:24717288). Natural neuropeptide hormones for dipeptidyl peptidase are the neuropeptide Y (NPY), peptide YY (PYY), substance P (TAC1) and brain natriuretic peptide 32 (NPPB) (PubMed:21314817). The plasma membrane form, in association with either DPP4, PLAUR or integrins, is involved in the pericellular proteolysis of the extracellular matrix (ECM), and hence promotes cell adhesion, migration and invasion through the ECM. Plays a role in tissue remodeling during development and wound healing. Participates in the cell invasiveness towards the ECM in malignant melanoma cancers. Enhances tumor growth progression by increasing angiogenesis, collagen fiber degradation and apoptosis and by reducing antitumor response of the immune system. Promotes glioma cell invasion through the brain parenchyma by degrading the proteoglycan brevican. Acts as a tumor suppressor in melanocytic cells through regulation of cell proliferation and survival in a serine protease activity-independent manner. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '04 Diseases of the immune system'] | 2 | Downloaded from PDB (6Y0F) | 6Y0F |
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Go to ligands | -8.2100 14.6900 100.8500 | |
| D0298 | Nicotinic acid receptor | Q8TDS4 | HCAR2_HUMAN | Niacin receptor 1, NIACR1, Hydroxycarboxylic acid receptor 2, HM74A, HCA2, GPR109A, G-protein coupled receptor HM74A, G-protein coupled receptor 109A | Acts as a high affinity receptor for both nicotinic acid (also known as niacin) and (D)-beta-hydroxybutyrate and mediates increased adiponectin secretion and decreased lipolysis through G(i)-protein-mediated inhibition of adenylyl cyclase. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet. Mediates nicotinic acid-induced apoptosis in mature neutrophils. Receptor activation by nicotinic acid results in reduced cAMP levels which may affect activity of cAMP-dependent protein kinase A and phosphorylation of target proteins, leading to neutrophil apoptosis. The rank order of potency for the displacement of nicotinic acid binding is 5-methyl pyrazole-3-carboxylic acid = pyridine-3-acetic acid > acifran > 5-methyl nicotinic acid = acipimox >> nicotinuric acid = nicotinamide. | Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '14 Diseases of the skin'] | 4 | Downloaded from PDB (7XK2) | 7XK2 |
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Go to ligands | 136.2300 125.0900 101.2900 | |
| D0299 | HIF-prolyl hydroxylase 1 | Q96KS0 | EGLN2_HUMAN | Prolyl hydroxylase domain-containing protein 1, PHD1, Hypoxia-inducible factor prolyl hydroxylase 1, HPH-3, HIF-PH1, HIF-PH, Estrogen-induced tag6, Estrogen-induced tag 6, Egl nine homolog 2, EIT6, EIT-6 | Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle. Also regulates susceptibility to normoxic oxidative neuronal death. Links oxygen sensing to cell cycle and primary cilia formation by hydroxylating the critical centrosome component CEP192 which promotes its ubiquitination and subsequent proteasomal degradation. Hydroxylates IKBKB, mediating NF-kappaB activation in hypoxic conditions. Target proteins are preferentially recognized via a LXXLAP motif. Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. | Enzyme | Oxidoreductase | Successful | ['03 Diseases of the blood or blood-forming organs'] | 1 | ['03 Diseases of the blood or blood-forming organs', '06 Mental, behavioural or neurodevelopmental disorders', '11 Diseases of the circulatory system', '16 Diseases of the genitourinary system'] | 4 | Downloaded from PDB (5V1B) | 5V1B |
|
Go to ligands | 15.3700 25.1000 -2.3800 | |
| D0300 | DNA topoisomerase I | P11387 | TOP1_HUMAN | DNA topoisomerase I | Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter. Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. | Enzyme | Isomerase | Successful | ['01 Certain infectious or parasitic diseases', '02 Neoplasms'] | 2 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms'] | 2 | Downloaded from PDB (1A36) | 1A36 |
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Go to ligands | 20.6300 18.6300 30.6800 | |
| D0301 | Phosphodiesterase 3A | Q14432 | PDE3A_HUMAN | cGMP-inhibited 3',5'-cyclic phosphodiesterase A, Phosphodiesterase 3A, Cyclic GMP-inhibited phosphodiesterase A, Cyclic GMP inhibited phosphodiesterase A, CGI-PDE A | Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. | Enzyme | Hydrolase | Successful | ['03 Diseases of the blood or blood-forming organs', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system'] | 3 | ['No clinical molecule'] | 0 | Downloaded from PDB (7KWE) | 7KWE |
|
Go to ligands | -22.4800 4.3600 -34.1800 | |
| D0302 | Plasminogen | P00747 | PLMN_HUMAN | Plasmin | In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells. Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. | Enzyme | Hydrolase | Successful | ['11 Diseases of the circulatory system', '16 Diseases of the genitourinary system', '22 Injury, poisoning or certain other consequences of external causes'] | 3 | ['08 Diseases of the nervous system', '09 Diseases of the visual system', '10 Diseases of the ear or mastoid process', '11 Diseases of the circulatory system'] | 4 | Downloaded from PDB (5UGG) | 5UGG |
|
Go to ligands | 26.6900 -5.3700 45.4000 | |
| D0303 | Matrix metalloproteinase-9 | P14780 | MMP9_HUMAN | Matrix metalloproteinase 9, GELB, CLG4B, 92 kDa type IV collagenase, 92 kDa gelatinase | Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide. May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '08 Diseases of the nervous system', '13 Diseases of the digestive system', '15 Diseases of the musculoskeletal system or connective tissue'] | 4 | Downloaded from PDB (6ESM) | 6ESM |
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Go to ligands | 1.9400 47.2000 18.8900 | |
| D0304 | Nicotinamide phosphoribosyltransferase | P43490 | NAMPT_HUMAN | Visfatin, PreBcell colonyenhancing factor 1, PreB cellenhancing factor, Pre-B-cell colony-enhancing factor 1, Pre-B cell-enhancing factor, PBEF1, PBEF, Nampt, NAmPRTase | It is the rate limiting component in the mammalian NAD biosynthesis pathway. The secreted form behaves both as a cytokine with immunomodulating properties and an adipokine with anti-diabetic properties, it has no enzymatic activity, partly because of lack of activation by ATP, which has a low level in extracellular space and plasma. Plays a role in the modulation of circadian clock function. NAMPT-dependent oscillatory production of NAD regulates oscillation of clock target gene expression by releasing the core clock component: CLOCK-ARNTL/BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression. Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6E68) | 6E68 |
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Go to ligands | 6.2700 -3.0800 45.2700 | |
| D0305 | Estrogen receptor | P03372 | ESR1_HUMAN | Nuclear receptor subfamily 3 group A member 1, NR3A1, Estradiol receptor, ESR, ER-alpha, ER | Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements, the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full-length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1. | Nuclear Hormone Receptor | - | Successful | ['02 Neoplasms', '05 Endocrine. Nutritional or metabolic diseases', '08 Diseases of the nervous system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system', '20 Developmental anomalies', '24 Factors influencing health status or contact with health services'] | 8 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '16 Diseases of the genitourinary system'] | 4 | Downloaded from PDB (7UJO) | 7UJO |
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Go to ligands | 14.1400 -25.9100 -20.9000 | |
| D0306 | Sodium/glucose cotransporter 1 | P13866 | SC5A1_HUMAN | Solute carrier family 5 member 1, Na(+)/glucose cotransporter 1, NAGT, High affinity sodium-glucose cotransporter | Efficient substrate transport in mammalian kidney is provided by the concerted action of a low affinity high capacity and a high affinity low capacity Na(+)/glucose cotransporter arranged in series along kidney proximal tubules. Actively transports glucose into cells by Na(+) cotransport with a Na(+) to glucose coupling ratio of 2:1. | Transporter | Electrochemical Potential-driven Transporters | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases', '11 Diseases of the circulatory system'] | 2 | Downloaded from PDB (7WMV) | 7WMV |
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Go to ligands | 101.3300 110.8800 113.7800 | |
| D0307 | Indoleamine 2,3-dioxygenase 1 | P14902 | I23O1_HUMAN | Indoleamine-pyrrole 2,3-dioxygenase, INDO, IDO-1, IDO | Involved in the peripheral immune tolerance, contributing to maintain homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses. Tryptophan shortage inhibits T lymphocytes division and accumulation of tryptophan catabolites induces T-cell apoptosis and differentiation of regulatory T-cells. Acts as a suppressor of anti-tumor immunity. Limits the growth of intracellular pathogens by depriving tryptophan. Protects the fetus from maternal immune rejection. Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway. | Enzyme | Oxidoreductase | Successful | ['06 Mental, behavioural or neurodevelopmental disorders'] | 1 | ['02 Neoplasms'] | 1 | Downloaded from PDB (8ABX) | 8ABX |
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Go to ligands | 20.8900 29.8100 15.7900 | |
| D0308 | Erbb4 tyrosine kinase receptor | Q15303 | ERBB4_HUMAN | Tyrosine kinase-type cell surface receptor HER4, Receptor tyrosine-protein kinase erbB-4, Proto-oncogene-like protein c-ErbB-4, P180erbB4, HER4 | Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis. Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms'] | 1 | Downloaded from PDB (2R4B) | 2R4B |
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Go to ligands | 14.4600 14.4100 -40.6900 | |
| D0309 | Adenosine A1 receptor | P30542 | AA1R_HUMAN | Adenosine receptor A1, A(1) adenosine receptor | The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Receptor for adenosine. | Receptor | - | Successful | ['11 Diseases of the circulatory system'] | 1 | ['05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '09 Diseases of the visual system', '11 Diseases of the circulatory system'] | 5 | Downloaded from PDB (5UEN) | 5UEN |
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Go to ligands | 53.7200 59.1200 141.4800 | |
| D0310 | Renal carcinoma antigen NY-REN-64 | Q9NWZ3 | IRAK4_HUMAN | Interleukin-1 receptor-associated kinase 4, IRAK-4 | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 4 | Downloaded from PDB (6EGE) | 6EGE |
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Go to ligands | -0.1700 -15.0100 -59.5100 | |
| D0311 | Hypoxia-inducible factor 1 alpha | Q16665 | HIF1A_HUMAN | bHLHe78, Transcription factor HIF-1, PASD8, PAS domain-containing protein 8, Member of PAS protein 1, MOP1, Hypoxia-inducible transcription factor (HIF)-1, Hypoxia-inducible factor 1-alpha, Hypoxia-inducible factor 1 A, Hypoxia inducible factor 1, HIF1-alpha, HIF1 alpha, HIF-1alpha, HIF-1-alpha, HIF-1 alpha, Class E basic helix-loop-helix protein 78, Basic-helix-loop-helix-PAS protein MOP1, ARNT-interacting protein, ARNT interacting protein | Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT, heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia. Functions as a master transcriptional regulator of the adaptive response to hypoxia. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '11 Diseases of the circulatory system'] | 2 | Downloaded from PDB (4H6J) | 4H6J |
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Go to ligands | 12.8100 -4.8000 -26.6300 | |
| D0312 | Choline kinase | P35790 | CHKA_HUMAN | ChoK, CHKA, CHETK-alpha | Has a key role in phospholipid biosynthesis and may contribute to tumor cell growth. Catalyzes the first step in phosphatidylcholine biosynthesis. Contributes to phosphatidylethanolamine biosynthesis. Phosphorylates choline and ethanolamine. Has higher activity with choline. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5FTG) | 5FTG |
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Go to ligands | -16.6400 9.7300 8.8500 | |
| D0313 | Stress-activated protein kinase 2b | Q15759 | MK11_HUMAN | Stress-activated protein kinase-2, SAPK2b, SAPK2, PRKM11, P38b, P38-2, P38 Mitogen-activated protein kinase beta, Mitogen-activated protein kinase p38 beta, Mitogen-activated protein kinase 11, MAPK 11, MAP kinase p38 beta, MAP kinase 11 | MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK11 functions are mostly redundant with those of MAPK14. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['08 Diseases of the nervous system', '15 Diseases of the musculoskeletal system or connective tissue'] | 2 | Downloaded from PDB (3GP0) | 3GP0 |
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Go to ligands | 19.9500 59.9600 23.9400 | |
| D0314 | C-C chemokine receptor type 5 | P51681 | CCR5_HUMAN | HIV-1 fusion coreceptor, HIV-1 fusion co-receptor, Chemokine receptor CCR5, CMKBR5, CHEMR13, CD195 antigen, CD195, CCR-5, CC-CKR-5, C-C CKR-5 | May play a role in the control of granulocytic lineage proliferation or differentiation. Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. | Receptor | - | Successful | ['01 Certain infectious or parasitic diseases'] | 1 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '12 Diseases of the respiratory system', '16 Diseases of the genitourinary system'] | 4 | Downloaded from PDB (6AKX) | 6AKX |
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Go to ligands | -1.4400 8.2300 -22.8700 | |
| D0315 | Tyrosine-protein kinase Mer | Q12866 | MERTK_HUMAN | Receptor tyrosine kinase MerTK, Proto-oncogene c-Mer | Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '08 Diseases of the nervous system'] | 2 | Downloaded from PDB (7AAZ) | 7AAZ |
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Go to ligands | -3.6600 26.8300 1.3800 | |
| D0316 | Intestinal maltase-glucoamylase | O43451 | MGA_HUMAN | MGAM | May serve as an alternate pathway for starch digestion when luminal alpha-amylase activity is reduced because of immaturity or malnutrition. May play a unique role in the digestion of malted dietary oligosaccharides used in food manufacturing. | Enzyme | Hydrolase | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['01 Certain infectious or parasitic diseases', '05 Endocrine, nutritional or metabolic diseases', '11 Diseases of the circulatory system', '15 Diseases of the musculoskeletal system or connective tissue'] | 4 | Downloaded from PDB (3L4Y) | 3L4Y |
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Go to ligands | -1.1000 -15.6500 -22.1300 | |
| D0317 | Endothelin B receptor | P24530 | EDNRB_HUMAN | Endothelin receptor type B, Endothelin receptor Non-selective type, Endothelin receptor B, ETRB, ET-BR, ET-B | Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Non-specific receptor for endothelin 1, 2, and 3. | Receptor | - | Successful | ['11 Diseases of the circulatory system'] | 1 | ['02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '16 Diseases of the genitourinary system'] | 4 | Downloaded from PDB (6IGK) | 6IGK |
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Go to ligands | 16.4600 27.4200 131.7600 | |
| D0318 | Apoptosis regulator Bcl-xL | Q07817 | B2CL1_HUMAN | Bcl2like protein 1, Bcl2L1, Bcl2-L-1, Bcl-XL, Bcl-2-like protein 1, BCLX, BCL2L, Apoptosis regulator Bcl-X | Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis. Potent inhibitor of cell death. | Factors and Regulators | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (7LH7) | 7LH7 |
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Go to ligands | 0.7800 -12.6300 1.0800 | |
| D0319 | Coagulation factor IIa | P00734 | THRB_HUMAN | Prothrombin, Coagulation factor II | Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing. | Enzyme | Hydrolase | Successful | ['03 Diseases of the blood or blood-forming organs', '05 Endocrine. Nutritional or metabolic diseases', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '13 Diseases of the digestive system', '16 Diseases of the genitourinary system'] | 6 | ['05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '11 Diseases of the circulatory system'] | 3 | Downloaded from PDB (5AFY) | 5AFY |
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Go to ligands | 82.9700 -9.7800 22.9600 | |
| D0320 | Ephrin type-A receptor 2 | P29317 | EPHA2_HUMAN | Tyrosine-protein kinase receptor ECK, Epithelial cell kinase, EphA2receptor, ECK | The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6HET) | 6HET |
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Go to ligands | -52.5100 -17.1300 87.3800 | |
| D0321 | Caspase-3 | P42574 | CASP3_HUMAN | Yama protein, SREBP cleavage activity 1, SCA-1, Protein Yama, Cysteine protease CPP32, Caspase 3, CPP32, CPP-32, CASP-3, Apopain | At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage. Involved in the activation cascade of caspases responsible for apoptosis execution. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6X8I) | 6X8I |
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Go to ligands | -3.7800 9.6300 6.9500 | |
| D0322 | PI3-kinase gamma | P48736 | PK3CG_HUMAN | p120-PI3K, p110gamma, Serine/threonine protein kinase PIK3CG, PtdIns-3-kinase subunit p110-gamma, PtdIns-3-kinase subunit gamma, PtdIns-3-kinase p110, Phosphoinositol-3 kinase, Phosphoinositide-3-kinase catalytic gamma polypeptide, Phosphoinositide 3-Kinase gamma, Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, gamma isoform, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma, PI3Kgamma, PI3K-gamma, PI3K, PI3-kinase subunit gamma, PI3-kinase p110 subunit gamma | Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '04 Diseases of the immune system', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '15 Diseases of the musculoskeletal system or connective tissue', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 7 | Downloaded from PDB (4ANV) | 4ANV |
|
Go to ligands | 43.5900 12.5900 32.0000 | |
| D0323 | Cyclin-dependent kinase 7 | P50613 | CDK7_HUMAN | TFIIH basal transcription factor complex kinase subunit, Serine/threonine-protein kinase 1, P39 Mo15, MO15, Cell division protein kinase 7, CDKN7, CDK-activating kinase 1, CDK-activating kinase, CAK1, CAK, 39 kDa protein kinase | Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Phosphorylation of POLR2A in complex with DNA promotes transcription initiation by triggering dissociation from DNA. Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53, this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition. Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (7B5Q) | 7B5Q |
|
Go to ligands | 82.0600 68.4700 57.7800 | |
| D0324 | C-X-C chemokine receptor type 4 | P61073 | CXCR4_HUMAN | Stromal cell-derived factor 1 receptor, SDF-1 receptor, NPYRL, Lipopolysaccharide-associated protein 3, Leukocyte-derived seven transmembrane domain receptor, LPS-associated protein 3, LESTR, LCR1, LAP-3, HM89, Fusin, FB22, Chemokine receptor CXCR4, CXCR-4, CXC-R4, CD184 antigen, CD184 | Involved in the AKT signaling cascade. Plays a role in regulation of cell migration, e. g. during wound healing. Acts as a receptor for extracellular ubiquitin, leading to enhanced intracellular calcium ions and reduced cellular cAMP levels. Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes. Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival. Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. | Receptor | - | Successful | ['02 Neoplasms'] | 1 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '04 Diseases of the immune system', '09 Diseases of the visual system', '12 Diseases of the respiratory system'] | 5 | Downloaded from PDB (3ODU) | 3ODU |
|
Go to ligands | 22.0200 -8.3600 70.2800 | |
| D0325 | Transient receptor potential cation channel V3 | Q8NET8 | TRPV3_HUMAN | Vanilloid receptor-like 3, VRL-3, TrpV3 | Putative receptor-activated non-selective calcium permeant cation channel. It is activated by innocuous (warm) temperatures and shows an increased response at noxious temperatures greater than 39 degrees Celsius. Activation exhibits an outward rectification. May associate with TRPV1 and may modulate its activity. Is a negative regulator of hair growth and cycling: TRPV3-coupled signaling suppresses keratinocyte proliferation in hair follicles and induces apoptosis and premature hair follicle regression (catagen). | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['21 Symptoms, signs or clinical findings, not elsewhere classified'] | 1 | Downloaded from PDB (6UW4) | 6UW4 |
|
Go to ligands | 169.9000 105.5600 176.1500 | |
| D0326 | B1 bradykinin receptor | P46663 | BKRB1_HUMAN | BRADYB1, BK-1 receptor, B1R | This is a receptor for bradykinin. Could be a factor in chronic pain and inflammation. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['09 Diseases of the visual system', '15 Diseases of the musculoskeletal system or connective tissue'] | 2 | Downloaded from PDB (7EIB) | 7EIB |
|
Go to ligands | 121.6700 100.8300 91.9000 | |
| D0327 | Voltage-gated sodium channel alpha Nav1.6 | Q9UQD0 | SCN8A_HUMAN | Voltage-gated sodium channel subunit alpha Nav1.6, Sodium channel protein type VIII subunit alpha, Sodium channel protein type 8 subunit alpha, SCN8A | Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. In macrophages and melanoma cells, isoform 5 may participate in the control of podosome and invadopodia formation. | Ion Channel | Channels/pores | Clinical trial | ['No approved drug'] | 0 | ['08 Diseases of the nervous system'] | 1 | Downloaded from PDB (8FHD) | 8FHD |
|
Go to ligands | 168.6700 176.6000 182.6000 | |
| D0328 | Beta-glucuronidase | P08236 | BGLR_HUMAN | Beta-G1 | Plays an important role in the degradation of dermatan and keratan sulfates. | Enzyme | Hydrolase | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['13 Diseases of the digestive system'] | 1 | Downloaded from PDB (3HN3) | 3HN3 |
|
Go to ligands | 81.3200 39.8300 87.4800 | |
| D0329 | Extracellular signal-regulated kinase 2 | P28482 | MK01_HUMAN | PRKM2, PRKM1, P42-MAPK, P42 Mitogen-activated protein kinase, Mitogen-activated protein kinase 2, Mitogen-activated protein kinase 1, MAPK 2, MAPK 1, MAP kinase isoform p42, MAP kinase 2, MAP kinase 1, ERT1, ERK-2 | MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2. Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '11 Diseases of the circulatory system'] | 2 | Downloaded from PDB (4ZZN) | 4ZZN |
|
Go to ligands | -13.7500 12.1200 41.1800 | |
| D0330 | Acyl-CoA desaturase | O00767 | SCD_HUMAN | hSCD1, Stearoyl-coenzyme A (Delta9) desaturase, Stearoyl-CoA desaturase, Membrane-bound 9 desaturase, Fatty acid desaturase, DesA3, Des A3, Delta-9-stearoyl desaturase, Delta-9 desaturase, Delta(9)-desaturase, 9 stearoyl-desaturase | Catalyzes the insertion of a cis double bond at the delta-9 position into fatty acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA. Gives rise to a mixture of 16:1 and 18:1 unsaturated fatty acids. Plays an important role in lipid biosynthesis. Plays an important role in regulating the expression of genes that are involved in lipogenesis and in regulating mitochondrial fatty acid oxidation. Plays an important role in body energy homeostasis. Contributes to the biosynthesis of membrane phospholipids, cholesterol esters and triglycerides. Stearyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates. | Enzyme | Oxidoreductase | Successful | ['01 Certain infectious or parasitic diseases'] | 1 | ['05 Endocrine, nutritional or metabolic diseases'] | 1 | Downloaded from PDB (4ZYO) | 4ZYO |
|
Go to ligands | 18.6000 70.6100 43.8000 | |
| D0331 | Thyroid hormone receptor beta | P10828 | THB_HUMAN | c-erbA-beta, c-erbA-2, THR1, Nuclear receptor subfamily 1 group A member 2, NR1A2, ERBA2 | High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Nuclear hormone receptor that can act as a repressor or activator of transcription. | Nuclear Hormone Receptor | - | Successful | ['05 Endocrine. Nutritional or metabolic diseases'] | 1 | ['05 Endocrine, nutritional or metabolic diseases', '14 Diseases of the skin'] | 2 | Downloaded from PDB (2J4A) | 2J4A |
|
Go to ligands | 3.8400 20.4000 32.3300 | |
| D0332 | Serine/threonine-protein kinase B-raf | P15056 | BRAF_HUMAN | V-Raf murine sarcoma viral oncogene homolog B1, RAFB1, Proto-oncogene B-Raf, P94, BRAF1, BRAF(V599E), BRAF serine/threonine kinase, B-raf protein, B-Raf | May play a role in the postsynaptic responses of hippocampal neuron. Phosphorylates MAP2K1, and thereby contributes to the MAP kinase signal transduction pathway. Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms'] | 1 | Downloaded from PDB (8C7Y) | 8C7Y |
|
Go to ligands | 0.5600 110.3100 17.8700 | |
| D0333 | Trace amine-associated receptor-1 | Q96RJ0 | TAAR1_HUMAN | Trace amine receptor 1, TaR-1, TAAR1 | Receptor for trace amines, including beta- phenylethylamine (b-PEA), p-tyramine (p-TYR), octopamine and tryptamine, with highest affinity for b-PEA and p-TYR. Unresponsive to classical biogenic amines,such as epinephrine and histamine and only partially activated by dopamine and serotonine. Trace amines are biogenic amines present in very low levels in mammalian tissues. Although some trace amineshave clearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Trace amines are likely to be involved in a variety of physiological functions that have yet to be fully understood. The signal transduced by this receptor is mediated by the G(s)-class of G-proteins which activate adenylate cyclase. | Receptor | - | Successful | ['06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders', '08 Diseases of the nervous system'] | 3 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system'] | 2 | Modelled with SWISS-MODEL (7CKY.1.E) | Homology |
|
Go to ligands | 108.3700 120.7900 136.5700 | |
| D0334 | PI3-kinase beta | P42338 | PK3CB_HUMAN | p110beta, PtdIns3kinase subunit p110beta, PtdIns3kinase subunit beta, PtdIns-3-kinase subunit p110-beta, PtdIns-3-kinase subunit beta, Phosphatidylinositol 4,5bisphosphate 3kinase catalytic subunitbeta isoform, Phosphatidylinositol 4,5bisphosphate 3kinase 110 kDa catalyticsubunit beta, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform, Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit beta, PIK3C1, PI3kinase subunit beta, PI3Kbeta, PI3K-beta, PI3-kinase subunit beta | Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation by G-protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (Phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 2 | Modelled with SWISS-MODEL (2Y3A.1.A) | Homology |
|
Go to ligands | 24.8400 -32.4000 -1.4700 | |
| D0335 | Prostaglandin D2 receptor 2 | Q9Y5Y4 | PD2R2_HUMAN | PTGDR2, Chemoattractant receptor-homologous molecule expressed on Th2 cells, CD294 | Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin- sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, ADRBK1/GRK2, GPRK5/GRK5 and GRK6. Receptoractivation is responsible, at least in part, in immune regulation and allergic/inflammation responses. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '04 Diseases of the immune system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '14 Diseases of the skin'] | 5 | Downloaded from PDB (6D26) | 6D26 |
|
Go to ligands | 4.5700 83.9800 281.1100 | |
| D0336 | Checkpoint kinase-1 | O14757 | CHK1_HUMAN | Serine/threonine-protein kinase Chk1, Chk1, Cell cycle checkpoint kinase, CHK1 checkpoint homolog | May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3. 1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest. Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4HYI) | 4HYI |
|
Go to ligands | 13.2200 -1.3200 12.0900 | |
| D0337 | Histone deacetylase 3 | O15379 | HDAC3_HUMAN | SMAP45, RPD32, RPD3-2, HD3 | Gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression. Probably participates in the regulation of transcription through its binding to the zinc-finger transcription factor YY1, increases YY1 repression activity. Required to repress transcription of the POU1F1 transcription factor. Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation. Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress. Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner. During the activation phase, promotes the accumulation of ubiquitinated ARNTL/BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and ARNTL/BMAL1. The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver. Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4A69) | 4A69 |
|
Go to ligands | 13.4700 85.4100 26.8600 | |
| D0338 | P2X purinoceptor 7 | Q99572 | P2RX7_HUMAN | Purinergic receptor 7, P2Z receptor, P2X7, Adenosine P2X7 receptor, ATP receptor | Responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Could function in both fast synaptic transmission and the ATP-mediated lysis of antigen-presenting cells. In the absence of its natural ligand, ATP, functions as a scavenger receptor in the recognition and engulfment of apoptotic cells. Receptor for ATP that acts as a ligand-gated ion channel. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '15 Diseases of the musculoskeletal system or connective tissue', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 8 | Modelled with SWISS-MODEL (6U9W.1.A) | Homology |
|
Go to ligands | 179.1700 152.2200 223.9900 | |
| D0339 | Histone deacetylase 4 | P56524 | HDAC4_HUMAN | KIAA0288, HD4 | Gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Deacetylates HSPA1A and HSPA1B at 'Lys-77' leading to their preferential binding to co-chaperone STUB1. Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (2VQM) | 2VQM |
|
Go to ligands | 20.4400 -13.5100 1.8800 | |
| D0340 | Androgen receptor | P10275 | ANDR_HUMAN | Testosterone receptor, Nuclear receptor subfamily 3 group C member 4, NR3C4, Dihydrotestosterone receptor, DHTR | Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation. Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3. Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. | Nuclear Hormone Receptor | - | Successful | ['02 Neoplasms', '05 Endocrine. Nutritional or metabolic diseases', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system'] | 7 | ['05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system', '24 Factors influencing health status or contact with health services'] | 8 | Downloaded from PDB (2AM9) | 2AM9 |
|
Go to ligands | 26.2200 2.3700 4.5800 | |
| D0341 | Chymase | P23946 | CMA1_HUMAN | Mast cell protease I, CYH, Alpha-chymase | Major secreted protease of mast cells with suspected roles in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '14 Diseases of the skin'] | 4 | Downloaded from PDB (4K69) | 4K69 |
|
Go to ligands | 63.3800 56.2100 -3.1500 | |
| D0342 | Carbonic anhydrase IX | Q16790 | CAH9_HUMAN | Renal cell carcinoma-associated antigen G250, RCC-associated antigen G250, PMW1, P54/58N, Membrane antigen MN, MN, G250 antigen (MN/CA IX/G250), G250, Carbonic anhydrase 9, Carbonate dehydratase IX, CAIX | Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia. Reversible hydration of carbon dioxide. | Enzyme | Lyase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (6G9U) | 6G9U |
|
Go to ligands | 20.4800 -17.1000 -21.2700 | |
| D0343 | Matrix metalloproteinase-14 | P50281 | MMP14_HUMAN | Membrane-type-1 matrix metalloproteinase, Membrane-type matrix metalloproteinase 1, MTMMP1, MT1MMP, MT1-MMP, MT-MMP 1, MMP-X1 | Activates progelatinase A. Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal connective tissues during development. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15. Involved in the formation of the fibrovascular tissues in association with pro-MMP2. Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis. Endopeptidase that degrades various components of the extracellular matrix such as collagen. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '13 Diseases of the digestive system'] | 2 | Downloaded from PDB (3MA2) | 3MA2 |
|
Go to ligands | 1.1200 4.4000 37.5000 | |
| D0344 | Multidrug resistance-associated protein 1 | P33527 | MRP1_HUMAN | MRP1, MRP, Leukotriene C(4) transporter, LTC4 transporter, ATP-binding cassette sub-family C member 1 | Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency. Mediates export of organic anions and drugs from the cytoplasm. | Transporter | Primary Active Transporters | Successful | ['15 Diseases of the musculoskeletal system or connective tissue'] | 1 | ['No clinical molecule'] | 0 | Downloaded from PDB (2CBZ) | 2CBZ |
|
Go to ligands | -18.3000 52.0800 4.7900 | |
| D0345 | Corticosteroid 11-beta-dehydrogenase 1 | P28845 | DHI1_HUMAN | HSD11B1, 11beta-HSD1A, 11HSD1, 11-beta-hydroxysteroid dehydrogenase 1, 11-beta-HSD1, 11-DH, 11 beta-hydroxysteroid dehydrogenase type 1 | Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7- ketocholesterol to 7-beta-hydroxycholesterol. | Enzyme | Oxidoreductase | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '04 Diseases of the immune system', '05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '09 Diseases of the visual system'] | 5 | Downloaded from PDB (4BB5) | 4BB5 |
|
Go to ligands | 26.5800 -9.6200 -34.7900 | |
| D0346 | Stress-activated protein kinase 2a | Q16539 | MK14_HUMAN | SAPK2A, P38 mitogen activatedprotein kinase, P38 Mitogen-activatedprotein kinase alpha, Mitogen-activated protein kinase p38 alpha, Mitogen-activated protein kinase 14, MXI2, MAX-interacting protein 2, MAPK 14, MAP kinase p38alpha, MAP kinase p38 alpha, MAP kinase MXI2, MAP kinase 14, Cytokine suppressive anti-inflammatory drug-binding protein, Cytokine suppressive anti-inflammatory drug binding protein, CSPB1, CSBP2, CSBP1, CSBP, CSAID-binding protein, CSAID binding protein, CRK1 | MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'. Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '15 Diseases of the musculoskeletal system or connective tissue', '22 Injury, poisoning or certain other consequences of external causes'] | 7 | Downloaded from PDB (3LFF) | 3LFF |
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Go to ligands | 18.5500 -6.4400 -17.4600 | |
| D0347 | Pyruvate kinase M2 | P14618 | KPYM_HUMAN | p58, Tumor M2-PK, Thyroid hormone-binding protein 1, THBP1, Pyruvate kinase muscle isozyme, Pyruvate kinase isozymes M1/M2, Pyruvate kinase PKM, Pyruvate kinase 2/3, PKM2, PK3, PK2, Opa-interacting protein 3, OIP3, OIP-3, Cytosolic thyroid hormone-binding protein, CTHBP | Stimulates POU5F1-mediated transcriptional activation. Plays a general role in caspase independent cell death of tumor cells. The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival. Promotes in a STAT1-dependent manner, the expression of the immune checkpoint protein CD274 in ARNTL/BMAL1-deficient macrophages. Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 2 | Downloaded from PDB (8G2E) | 8G2E |
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Go to ligands | 1.4100 -5.9900 -13.5900 | |
| D0348 | Adrenergic receptor alpha-2A | P08913 | ADA2A_HUMAN | Alpha-2AAR, Alpha-2A adrenoreceptor, Alpha-2A adrenoceptor, Alpha-2A adrenergic receptor, Alpha-2 adrenergic receptor subtype C10, ADRAR, ADRA2R | The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol. Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. | Receptor | - | Successful | ['06 Mental, behavioural or neurodevelopmental disorders'] | 1 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 3 | Downloaded from PDB (6KUX) | 6KUX |
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Go to ligands | -2.4100 -6.9000 -21.6800 | |
| D0349 | Dipeptidyl peptidase 9 | Q86TI2 | DPP9_HUMAN | Dipeptidyl peptidase-like protein 9, Dipeptidyl peptidase IX, Dipeptidyl peptidase IV-related protein 2, DPRP2, DPRP-2, DPP IX, DPLP9, DP9 | Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '04 Diseases of the immune system'] | 2 | Downloaded from PDB (7ZXS) | 7ZXS |
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Go to ligands | 42.9000 -97.9000 -89.7500 | |
| D0350 | Complement factor D | P00746 | CFAD_HUMAN | Properdin factor D, PFD, DF, C3 convertase activator, Adipsin | Factor D cleaves factor B when the latter is complexed with factor C3b, activating the C3bbb complex, which then becomes the C3 convertase of the alternate pathway. Its function is homologous to that of C1s in the classical pathway. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['03 Diseases of the blood or blood-forming organs', '05 Endocrine, nutritional or metabolic diseases', '09 Diseases of the visual system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 4 | Downloaded from PDB (5NAT) | 5NAT |
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Go to ligands | 2.1400 -5.1400 8.7000 | |
| D0351 | Cathepsin D | P07339 | CATD_HUMAN | CPSD, CD | Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease. Acid protease active in intracellular protein breakdown. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['08 Diseases of the nervous system'] | 1 | Downloaded from PDB (6QCB) | 6QCB |
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Go to ligands | 11.4900 18.0400 7.8100 | |
| D0352 | Aminopeptidase N | P15144 | AMPN_HUMAN | Myeloid plasma membrane glycoprotein CD13, Microsomal aminopeptidase, HAPN, Gp150, Aminopeptidase M, Alanyl aminopeptidase, ANPEP | Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May play a critical role in the pathogenesis of cholesterol gallstone disease. May be involved in the metabolism of regulatory peptides of diverse cell types, responsible for the processing of peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines. Found to cleave antigen peptides bound to major histocompatibility complex class II molecules of presenting cells and to degrade neurotransmitters at synaptic junctions. Is also implicated as a regulator of IL-8 bioavailability in the endometrium, and therefore may contribute to the regulation of angiogenesis. Is used as a marker for acute myeloid leukemia and plays a role in tumor invasion. In case of human coronavirus 229E (HCoV-229E) infection, serves as receptor for HCoV-229E spike glycoprotein. Mediates as well human cytomegalovirus (HCMV) infection. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['14 Diseases of the skin'] | 1 | Downloaded from PDB (4FYT) | 4FYT |
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Go to ligands | 107.3400 17.5500 19.0700 | |
| D0353 | Integrin alpha-V/beta-3 | P06756+P05106 | ITAV_HUMAN+ITB3_HUMAN | Integrin alphaVbeta3, Integrin alpha-v beta-3, Integrin alpha V beta 3, Alpha(v)beta(3) Integrin, Alpha v beta 3 integrin | Receptor for phagocytosis on macrophages or dendritic cells. In cancer and other diseases, its role in angiogenesis is directly responsible to providing blood supply to problematic overgrowths. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '09 Diseases of the visual system', '11 Diseases of the circulatory system', '15 Diseases of the musculoskeletal system or connective tissue'] | 4 | Downloaded from PDB (6MK0) | 6MK0 |
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Go to ligands | 19.4500 41.2700 37.2800 | |
| D0354 | RAC-alpha serine/threonine-protein kinase | P31749 | AKT1_HUMAN | RAC-PK-alpha, RAC, Proto-oncogene c-Akt, Protein kinase B alpha, PKB alpha | AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro-apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '20 Developmental anomalies', '22 Injury, poisoning or certain other consequences of external causes'] | 5 | Downloaded from PDB (4GV1) | 4GV1 |
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Go to ligands | -21.4300 4.1400 9.3000 | |
| D0355 | Cathepsin S | P25774 | CATS_HUMAN | Cysteine protease cathepsin S | Key protease responsible for the removal of the invariant chain from MHC class II molecules. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin L. Thiol protease. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['04 Diseases of the immune system', '05 Endocrine, nutritional or metabolic diseases', '08 Diseases of the nervous system', '13 Diseases of the digestive system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 5 | Downloaded from PDB (3OVX) | 3OVX |
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Go to ligands | 25.8800 37.2200 19.3200 | |
| D0356 | Gonadotropin-releasing hormone receptor | P30968 | GNRHR_HUMAN | Hypothalamic gonadotropin-releasing hormone receptor, Gonadotrophin releasing hormone receptor, GnRH-R, GnRH receptor, GRHR | Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This receptor mediates its action by association with G-proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act as an inhibitor of GnRH-R signaling. | Receptor | - | Successful | ['02 Neoplasms', '05 Endocrine. Nutritional or metabolic diseases', '16 Diseases of the genitourinary system', '20 Developmental anomalies'] | 4 | ['02 Neoplasms', '16 Diseases of the genitourinary system'] | 2 | Downloaded from PDB (7BR3) | 7BR3 |
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Go to ligands | -26.0000 18.4600 -9.5200 | |
| D0357 | Glycine transporter GlyT-1 | P48067 | SC6A9_HUMAN | Solute carrier family 6 member 9, Sodium- and chloride-dependent glycine transporter 1, Glycine type-1 transporter, Glycine transporter type 1, GlyT1, GlyT-1 | May play a role in regulation of glycine levels in NMDA receptor-mediated neurotransmission. Terminates the action of glycine by its high affinity sodium-dependent reuptake into presynaptic terminals. | Transporter | Electrochemical Potential-driven Transporters | Clinical trial | ['No approved drug'] | 0 | ['06 Mental, behavioural or neurodevelopmental disorders'] | 1 | Downloaded from PDB (6ZBV) | 6ZBV |
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Go to ligands | -3.5000 6.2200 37.4300 | |
| D0358 | Adrenergic receptor alpha-2C | P18825 | ADA2C_HUMAN | Subtype C4, Alpha-2CAR, Alpha-2C adrenoreceptor, Alpha-2C adrenoceptor, Alpha-2C adrenergic receptor, Alpha-2 adrenergic receptor subtype C4, ADRA2RL2, ADRA2L2 | Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. | Receptor | - | Successful | ['01 Certain infectious or parasitic diseases', '05 Endocrine. Nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '09 Diseases of the visual system', '11 Diseases of the circulatory system'] | 5 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '16 Diseases of the genitourinary system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 6 | Downloaded from PDB (6KUW) | 6KUW |
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Go to ligands | -31.9700 -16.7600 54.1000 | |
| D0359 | LCK tyrosine protein kinase | P06239 | LCK_HUMAN | p56-LCK, Tyrosine-protein kinase Lck, T cell-specific protein-tyrosine kinase, Proto-oncogene tyrosine-protein kinase LCK, Proto-oncogene Lck, Protein YT16, Lymphocyte cell-specific protein-tyrosine kinase, Leukocyte C-terminal Src kinase, LSK, LCK p59-Fyn, LCK Protooncogene Syn | Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP. Interacts with FYB2. Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '11 Diseases of the circulatory system'] | 3 | Downloaded from PDB (6PDJ) | 6PDJ |
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Go to ligands | 1.4100 1.1200 -9.2200 | |
| D0360 | Cyclin-dependent kinase 2 | P24941 | CDK2_HUMAN | Sin3 associated polypeptide, SIN3-associated protein, P33 protein kinase, Cell division protein kinase 2, CDKN2 | Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression, controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2, activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1. Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis, regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability. Phosphorylates CDK2AP2. Serine/threonine-protein kinase involved in the control of the cell cycle, essential for meiosis, but dispensable for mitosis. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4FKL) | 4FKL |
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Go to ligands | -0.9400 6.3900 26.5800 | |
| D0361 | Glycogen synthase kinase-3 beta | P49841 | GSK3B_HUMAN | Serine/threonine-protein kinase GSK3B, GSK-3 beta | Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2. Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation. Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation. Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation. Regulates the circadian rhythmicity of hippocampal long-term potentiation and ARNTL/BMLA1 and PER2 expression. Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer. Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '08 Diseases of the nervous system', '20 Developmental anomalies'] | 3 | Downloaded from PDB (1Q5K) | 1Q5K |
|
Go to ligands | 21.1700 25.2000 6.3800 | |
| D0362 | Protein kinase C alpha | P17252 | KPCA_HUMAN | Protein kinase C alpha type, PRKACA, PKCalpha, PKCA, PKC-alpha, PKC-A | Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42. Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. | Enzyme | Transferase | Successful | ['08 Diseases of the nervous system'] | 1 | ['22 Injury, poisoning or certain other consequences of external causes'] | 1 | Downloaded from PDB (4RA4) | 4RA4 |
|
Go to ligands | 32.5400 -3.9500 14.4600 | |
| D0363 | Nitric-oxide synthase endothelial | P29474 | NOS3_HUMAN | Nitric oxide synthase, endothelial, NOSIII, NOS,type III, NOS type III, Endothelial nitric oxide synthase, Endothelial NOS, ENOS, EC-NOS, Constitutive NOS, CNOS | NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. | Enzyme | Oxidoreductase | Clinical trial | ['No approved drug'] | 0 | ['11 Diseases of the circulatory system', '22 Injury, poisoning or certain other consequences of external causes'] | 2 | Downloaded from PDB (6PP1) | 6PP1 |
|
Go to ligands | 105.0600 -9.6700 -220.0300 | |
| D0364 | Caspase-7 | P55210 | CASP7_HUMAN | MCH3, ICE-like apoptotic protease 3, ICE-LAP3, CMH-1, CASP-7, Apoptotic protease Mch-3 | Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death. Involved in the activation cascade of caspases responsible for apoptosis execution. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['12 Diseases of the respiratory system'] | 1 | Downloaded from PDB (2QL9) | 2QL9 |
|
Go to ligands | -45.0800 23.9000 -5.1000 | |
| D0365 | Bacterial Lethal factor | P15917 | LEF_BACAN | lef, Anthrax lethal toxin endopeptidase component, Anthrax lethal factor, ALF | One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. LF is the lethal factor that, when associated with PA, causes death. LF is not toxic by itself. It is a protease that cleaves the N-terminal of most dual specificity mitogen-activated protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5). Cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes. There may be other cytosolic targets of LF involved in cytotoxicity. The proteasome may mediate a toxic process initiated by LF in the cell cytosol involving degradation of unidentified molecules that are essential for macrophage homeostasis. This is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases'] | 1 | Downloaded from PDB (4PKW) | 4PKW |
|
Go to ligands | 11.9000 19.3200 26.3800 | |
| D0366 | Tissue factor | P13726 | TF_HUMAN | Thromboplastin, TF, F3, Coagulation factor III, CD142 antigen | Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited protolysis. TF plays a role in normal hemostasis by initiating the cell-surface assemblyand propagation of the coagulation protease cascade. | Enzyme | Hydrolase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '12 Diseases of the respiratory system', '16 Diseases of the genitourinary system'] | 3 | Downloaded from PDB (6R2W) | 6R2W |
|
Go to ligands | -1.3100 4.9700 22.2900 | |
| D0367 | E-selectin | P16581 | LYAM2_HUMAN | Leukocyte-endothelial cell adhesion molecule 2, LECAM2, Endothelial leukocyte adhesion molecule 1, ELAM1, ELAM-1, CD62E antigen, CD62E, CD62 antigen-like family member E | Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in capillary morphogenesis. Cell-surface glycoprotein having a role in immunoadhesion. | Other | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '03 Diseases of the blood or blood-forming organs', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '14 Diseases of the skin'] | 5 | Downloaded from PDB (1G1T) | 1G1T |
|
Go to ligands | 35.2800 109.6700 40.8200 | |
| D0368 | Orexin receptor type 1 | O43613 | OX1R_HUMAN | Ox1r, Ox1-R, Ox-1-R, Orexin-1 receptor, Hypocretin receptor type 1, HFGAN72 receptor, 7-transmembrane G-protein coupledneuropeptide receptor | Triggers an increase in cytoplasmic Ca(2+) levels in response to orexin-A binding. Moderately selective excitatory receptor for orexin-A and, with a lower affinity, for orexin-B neuropeptide. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['06 Mental, behavioural or neurodevelopmental disorders', '07 Sleep-wake disorders'] | 2 | Downloaded from PDB (6TOT) | 6TOT |
|
Go to ligands | 23.6800 -33.8600 81.6800 | |
| D0369 | Rho-associated protein kinase 2 | O75116 | ROCK2_HUMAN | p164 ROCK-2, Rho-associated, coiled-coil-containing protein kinase II, Rho-associated, coiled-coil-containing protein kinase 2, Rho kinase 2, ROCK-II, KIAA0619 | Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation. Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. | Enzyme | Transferase | Successful | ['04 Diseases of the immune system'] | 1 | ['01 Certain infectious or parasitic diseases', '04 Diseases of the immune system', '09 Diseases of the visual system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 5 | Downloaded from PDB (7JNT) | 7JNT |
|
Go to ligands | 10.7100 19.8400 38.6900 | |
| D0370 | Dual specificity protein kinase TTK | P33981 | TTK_HUMAN | Tyrosine threonine kinase, Phosphotyrosine picked threonine-protein kinase, PYT, MPS1L1 | Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint. Phosphorylates proteins on serine, threonine, and tyrosine. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4JS8) | 4JS8 |
|
Go to ligands | -0.5400 18.7100 11.8700 | |
| D0371 | Methionine aminopeptidase 2 | P50579 | MAP2_HUMAN | Peptidase M 2, P67eIF2, P67, MetAP 2, METAP2, Initiation factor 2 associated 67 kDa glycoprotein, (MetAP)-2 | Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases'] | 2 | Downloaded from PDB (6QEJ) | 6QEJ |
|
Go to ligands | 25.3400 20.2700 16.6700 | |
| D0372 | Farnesyl protein transferase | P49354+P49356 | FNTA_HUMAN+FNTB_HUMAN | Ras proteins prenyltransferase, Protein farnesyltransferase, Ftase, CAAX farnesyltransferase | Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. Contributes to the transfer of a farnesyl or geranylgeranyl moiety from farnesyl or geranylgeranyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. May positively regulate neuromuscular junction development downstream of MUSK via its function in RAC1prenylation and activation. | Enzyme | Transferase | Successful | ['20 Developmental anomalies'] | 1 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms'] | 2 | Downloaded from PDB (1LD8) | 1LD8 |
|
Go to ligands | 15.8800 132.7200 -1.5900 | |
| D0373 | Pattern recognition receptor NOD2 | Q9HC29 | NOD2_HUMAN | Nucleotidebinding oligomerization domaincontaining protein 2, Nucleotide-binding oligomerization domain-containing protein 2, Inflammatory bowel disease protein 1, IBD1, Caspase recruitment domaincontaining protein 15, Caspase recruitment domain-containing protein 15, CARD15 | Upon stimulation by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, binds the proximal adapter receptor-interacting RIPK2, which recruits ubiquitin ligases as XIAP, BIRC2, BIRC3, INAVA and the LUBAC complex, triggering activation of MAP kinases and activation of NF-kappa-B signaling. This in turn leads to the transcriptional activation of hundreds of genes involved in immune response. Required for MDP-induced NLRP1-dependent CASP1 activation and IL1B release in macrophages. Component of an autophagy-mediated antibacterial pathway together with ATG16L1. Plays also a role in sensing single-stranded RNA (ssRNA) from viruses. Interacts with mitochondrial antiviral signaling/MAVS, leading to activation of interferon regulatory factor-3/IRF3 and expression of type I interferon. Involved in gastrointestinal immunity. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '05 Endocrine, nutritional or metabolic diseases'] | 2 | Modelled with SWISS-MODEL (5IRM.1.A) | Homology |
|
Go to ligands | 3.4300 -6.1300 13.0700 | |
| D0374 | Geranylgeranyl transferase I | P53609 | PGTB1_HUMAN | Type I protein geranyl-geranyltransferase subunit beta, Type I protein geranyl-geranyltransferase beta subunit of Saccharomyces cerevisiae, RAS proteins geranylgeranyltransferase beta subunit, PGGT, Geranylgeranyl transferase type-1 subunit beta, Geranylgeranyl transferase type I subunit beta, GGTase-I-beta of Saccharomyces cerevisiae, GGTase-I-beta, CDC43 | Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. Known substrates include RAC1, RAC2, RAP1A and RAP1B. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Modelled with SWISS-MODEL (1TNU.1.B) | Homology |
|
Go to ligands | 34.5900 89.5600 67.1800 | |
| D0375 | Carbonic anhydrase I | P00915 | CAH1_HUMAN | Carbonic anhydrase B, Carbonic anhydrase 1, Carbonate dehydratase I, CAB | Can hydrates cyanamide to urea. Reversible hydration of carbon dioxide. | Enzyme | Lyase | Successful | ['09 Diseases of the visual system', '14 Diseases of the skin'] | 2 | ['02 Neoplasms', '15 Diseases of the musculoskeletal system or connective tissue'] | 2 | Downloaded from PDB (7Q0D) | 7Q0D |
|
Go to ligands | 28.9700 -0.1400 -2.3800 | |
| D0376 | Proteasome beta-8 | P28062 | PSB8_HUMAN | Y2, Really interesting new gene 10 protein, RING10, Proteasome subunit beta-5i, Proteasome subunit beta type-8, Proteasome component C13, PSMB5i, Multicatalytic endopeptidase complex subunit C13, Macropain subunit C13, Low molecular mass protein 7, LMP7 | The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB5 by PSMB8 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues. Acts as a major component of interferon gamma-induced sensitivity. Plays a key role in apoptosis via the degradation of the apoptotic inhibitor MCL1. May be involved in the inflammatory response pathway. In cancer cells, substitution of isoform 1 (E2) by isoform 2 (E1) results in immunoproteasome deficiency. Required for the differentiation of preadipocytes into adipocytes. The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (7AWE) | 7AWE |
|
Go to ligands | -54.0700 21.7900 11.7200 | |
| D0377 | Phosphodiesterase 2A | O00408 | PDE2A_HUMAN | cGMP-dependent 3',5'-cyclic phosphodiesterase, PDE-II, Cyclic-GMP phosphodiesterase, Cyclic GMP-stimulated phosphodiesterase, Cyclic GMP stimulated phosphodiesterase, CGSPDE, CGS-PDE | Plays an important role in growth and invasion of malignant melanoma cells (e. g. pseudomyxoma peritonei (PMP) cell line). Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '13 Diseases of the digestive system'] | 3 | Downloaded from PDB (5U00) | 5U00 |
|
Go to ligands | 8.0900 4.7400 7.0500 | |
| D0378 | Thromboxane-A synthase | P24557 | THAS_HUMAN | Thromboxane A2 synthase, TXS, TXA synthase, Cytochrome P450 5A1, CYP5A1, CYP5 | endoplasmic reticulum membrane, 12-hydroxyheptadecatrienoic acid synthase activity, thromboxane-A synthase activity, cyclooxygenase pathway, icosanoid metabolic process. | Enzyme | Oxidoreductase | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases', '11 Diseases of the circulatory system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system'] | 4 | Downloaded from PDB (5VCE) | 5VCE |
|
Go to ligands | 22.6300 33.2600 138.8200 | |
| D0379 | Inhibitor of nuclear factor kappa-B kinase beta | O14920 | IKKB_HUMAN | Nuclear factor NF-kappa-B inhibitor kinase beta, NFKBIKB, Inhibitor of nuclear factor kappa-B kinase subunit beta, IkBKB, IKKB, IKK2, IKK-beta, IKK-B, I-kappa-B-kinase beta, I-kappa-B kinase 2 | Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation. Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['08 Diseases of the nervous system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 3 | Downloaded from PDB (4KIK) | 4KIK |
|
Go to ligands | 50.2100 31.0300 -57.2900 | |
| D0380 | TYK2 tyrosine kinase | P29597 | TYK2_HUMAN | Non-receptor tyrosine-protein kinase TYK2 | Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain. | Enzyme | Transferase | Successful | ['14 Diseases of the skin'] | 1 | ['12 Diseases of the respiratory system', '15 Diseases of the musculoskeletal system or connective tissue'] | 2 | Downloaded from PDB (4WOV) | 4WOV |
|
Go to ligands | 8.2900 -3.2500 2.4400 | |
| D0381 | Beta-secretase 1 | P56817 | BACE1_HUMAN | Membrane-associated aspartic protease 2, Memapsin-2, KIAA1149, Beta-site amyloid precursor protein cleaving enzyme 1, Beta-site APP cleaving enzyme 1, BACE, Aspartyl protease 2, Asp 2, ASP2 | Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. Cleaves APP with much more catalytic efficiency than for the wild-type. Responsible for the proteolytic processing of the amyloid precursor protein (APP). | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['08 Diseases of the nervous system'] | 1 | Downloaded from PDB (7MYI) | 7MYI |
|
Go to ligands | 19.9600 53.8200 88.3700 | |
| D0382 | 5-HT 7 receptor | P34969 | 5HT7R_HUMAN | Serotonin receptor 7, 5HT7, 5-hydroxytryptamine receptor 7, 5-HT7 receptor, 5-HT7, 5-HT-X, 5-HT-7 | The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system'] | 2 | Downloaded from PDB (7XTC) | 7XTC |
|
Go to ligands | 89.8800 110.2600 82.2800 | |
| D0383 | Aromatase | P11511 | CP19A_HUMAN | P-450AROM, Estrogen synthetase, Estrogen synthase, Cytochrome P450 19A1, Cytochrome P-450AROM, CYPXIX, CYP19, CYAR, ARO1 | Catalyzes the formation of aromatic C18 estrogens from C19 androgens. | Enzyme | Oxidoreductase | Successful | ['02 Neoplasms', '05 Endocrine. Nutritional or metabolic diseases'] | 2 | ['08 Diseases of the nervous system', '13 Diseases of the digestive system', '16 Diseases of the genitourinary system'] | 3 | Downloaded from PDB (5JKV) | 5JKV |
|
Go to ligands | 86.2300 54.3100 45.3400 | |
| D0384 | DNA-dependent protein kinase catalytic | P78527 | PRKDC_HUMAN | p460, HYRC1, HYRC, DNPK1, DNA-dependent protein kinase catalytic subunit, DNA-PKcs, DNA-PK catalytic subunit | Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. Must be bound to DNA to express its catalytic properties. Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step. Required to protect and align broken ends of DNA. May also act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage. Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. Also involved in modulation of transcription. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX, thereby regulating DNA damage response mechanism. Phosphorylates DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, XRCC1, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2. Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA. Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D. Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Modelled with SWISS-MODEL (7OTV.1.A) | Homology |
|
Go to ligands | 155.9000 159.6100 128.4300 | |
| D0385 | Phosphodiesterase 4D | Q08499 | PDE4D_HUMAN | cAMP-specific 3',5'-cyclic phosphodiesterase 4D, PDE43, DPDE3 | Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. | Enzyme | Hydrolase | Successful | ['21 Symptoms, signs or clinical findings, not elsewhere classified'] | 1 | ['06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '12 Diseases of the respiratory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 6 | Downloaded from PDB (5WH6) | 5WH6 |
|
Go to ligands | 7.0300 -2.6600 58.5400 | |
| D0386 | TNF alpha converting enzyme | P78536 | ADA17_HUMAN | TNFalpha converting enzyme, TNF-alpha-converting enzyme, TNF-alpha converting enzyme, TNF-alpha convertase, TACE, Snake venom-like protease, Disintegrin and metalloproteinase domain-containing protein 17, CSVP, CD156b antigen, CD156b, ADAM 17, A disintegrin and metalloproteinase domain 17 | Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT). Plays a role in the proteolytic processing of ACE2. Plays a role in hemostasis through shedding of GP1BA, the platelet glycoprotein Ib alpha chain. Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3. Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '15 Diseases of the musculoskeletal system or connective tissue'] | 2 | Downloaded from PDB (2DDF) | 2DDF |
|
Go to ligands | 48.5200 33.5000 43.1800 | |
| D0387 | Retinoic acid receptor RXR-alpha | P19793 | RXRA_HUMAN | Retinoid X receptor alpha, RXRalpha, Nuclear receptor subfamily 2 group B member 1, NR2B1 | Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes. Receptor for retinoic acid. | Nuclear Hormone Receptor | - | Successful | ['02 Neoplasms'] | 1 | ['No clinical molecule'] | 0 | Downloaded from PDB (7A77) | 7A77 |
|
Go to ligands | 18.3100 3.9800 24.2900 | |
| D0388 | Cysteines of Keap1 | Q14145 | KEAP1_HUMAN | Kelch-like protein 19-Cysteines, Kelch-like ECH-associated protein 1-Cysteines, KLHL19-Cysteines, KIAA0132-Cysteines, INrf2-Cysteines, Cytosolic inhibitor of Nrf2-Cysteines | Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome. Acts as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. | Factors and Regulators | - | Clinical trial | ['No approved drug'] | 0 | ['11 Diseases of the circulatory system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 2 | Downloaded from PDB (6TYM) | 6TYM |
|
Go to ligands | -10.3400 -24.1800 -17.6800 | |
| D0389 | Phosphodiesterase 10A | Q9Y233 | PDE10_HUMAN | cAMP and cAMPinhibited cGMP 3',5'cyclic phosphodiesterase 10A, cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A | Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate. May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition. Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders', '08 Diseases of the nervous system', '13 Diseases of the digestive system'] | 5 | Downloaded from PDB (5C28) | 5C28 |
|
Go to ligands | 3.5500 13.5500 43.7000 | |
| D0390 | Sphingosine-1-phosphate receptor 1 | P21453 | S1PR1_HUMAN | Sphingosine 1-phosphate receptor Edg-1, S1P1, S1P receptor Edg-1, S1P receptor 1, Endothelial differentiation G-protein coupled receptor 1, CHEDG1, CD363 | Signaling leads to the activation of RAC1, SRC, PTK2/FAK1 and MAP kinases. Plays an important role in cell migration, probably via its role in the reorganization of the actin cytoskeleton and the formation of lamellipodia in response to stimuli that increase the activity of the sphingosine kinase SPHK1. Required for normal chemotaxis toward sphingosine 1-phosphate. Required for normal embryonic heart development and normal cardiac morphogenesis. Plays an important role in the regulation of sprouting angiogenesis and vascular maturation. Inhibits sprouting angiogenesis to prevent excessive sprouting during blood vessel development. Required for normal egress of mature T-cells from the thymus into the blood stream and into peripheral lymphoid organs. Plays a role in the migration of osteoclast precursor cells, the regulation of bone mineralization and bone homeostasis. Plays a role in responses to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by pulmonary endothelial cells and in the protection against ventilator-induced lung injury. G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins. | Receptor | - | Successful | ['08 Diseases of the nervous system', '13 Diseases of the digestive system'] | 2 | ['02 Neoplasms', '04 Diseases of the immune system', '05 Endocrine, nutritional or metabolic diseases', '09 Diseases of the visual system', '11 Diseases of the circulatory system', '13 Diseases of the digestive system', '14 Diseases of the skin', '15 Diseases of the musculoskeletal system or connective tissue'] | 8 | Downloaded from PDB (7TD4) | 7TD4 |
|
Go to ligands | 139.6700 132.6900 161.7600 | |
| D0391 | Tubulin beta-1 chain | Q9H4B7 | TBB1_HUMAN | TUBB1 | Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. | Other | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Modelled with SWISS-MODEL (6TIS.1.B) | Homology |
|
Go to ligands | 17.5800 72.1100 97.5700 | |
| D0392 | Sphingosine kinase 1 | Q9NYA1 | SPHK1_HUMAN | SPK 1, SPK, SPHK1, SK 1, Acetyltransferase SPHK1 | Acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo-dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol. In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis. Involved in the regulation of inflammatory response and neuroinflammation. Via the product sphingosine 1-phosphate, stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF-kappa-B in response to TNF signaling leading to IL17 secretion. In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES inducion through p38 MAPK signaling pathway. Involved in endocytic membrane trafficking induced by sphingosine, recruited to dilate endosomes, also plays a role on later stages of endosomal maturation and membrane fusion independently of its kinase activity. In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA. Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '06 Mental, behavioural or neurodevelopmental disorders'] | 2 | Downloaded from PDB (4V24) | 4V24 |
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Go to ligands | -5.4100 2.9200 -31.8200 | |
| D0393 | Telomerase reverse transcriptase | O14746 | TERT_HUMAN | Telomerase-associated protein 2, Telomerase catalytic subunit, TRT, TP2, TCS1, HEST2, EST2 | Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt signaling. Plays important roles in aging and antiapoptosis. Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '03 Diseases of the blood or blood-forming organs', '08 Diseases of the nervous system', '09 Diseases of the visual system', '11 Diseases of the circulatory system'] | 6 | Downloaded from PDB (5UGW) | 5UGW |
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Go to ligands | -55.5600 44.7000 149.9500 | |
| D0394 | Prolyl endopeptidase | P48147 | PPCE_HUMAN | Post-proline cleaving enzyme, PREP, PE | Cleaves peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '06 Mental, behavioural or neurodevelopmental disorders', '13 Diseases of the digestive system'] | 4 | Downloaded from PDB (3DDU) | 3DDU |
|
Go to ligands | -7.1100 13.8800 29.0000 | |
| D0395 | Solute carrier family 40 member 1 | Q9NP59 | S40A1_HUMAN | SLC11A3, MSTP079, IREG1, Ferroportin-1, FPN1 | Mediates iron efflux in the presence of a ferroxidase (hephaestin and/or ceruloplasmin). May be involved in iron export from duodenal epithelial cell and also in transfer of iron between maternal and fetal circulation. | Transporter | Electrochemical Potential-driven Transporters | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '03 Diseases of the blood or blood-forming organs'] | 2 | Downloaded from PDB (8DL7) | 8DL7 |
|
Go to ligands | 117.8700 103.7600 129.8800 | |
| D0396 | G-protein coupled bile acid receptor 1 | Q8TDU6 | GPBAR_HUMAN | hGPCR19, hBG37, TGR5, Membrane-type receptor for bile acids, M-BAR, G-protein coupled receptor GPCR19, BG37 | Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macrophage functions by bile acids. Receptor for bile acid. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases'] | 1 | Downloaded from PDB (7CFM) | 7CFM |
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Go to ligands | 99.1400 118.5600 112.9000 | |
| D0397 | Serine/threonine-protein kinase pim-2 | Q9P1W9 | PIM2_HUMAN | Pim-2h, PIM2 | Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression, the regulation of cap-dependent protein translation and through survival signaling by phosphorylation of a pro-apoptotic protein, BAD. Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase transcriptional activity. The stabilization of MYC exerted by PIM2 might explain partly the strong synergism between these 2 oncogenes in tumorigenesis. Regulates cap-dependent protein translation in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner and in parallel to the PI3K-Akt pathway. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti- apoptotic protein Bcl-X(L)/BCL2L1. Promotes cell survival in response to a variety of proliferative signals via positive regulation of the I-kappa-B kinase/NF-kappa-B cascade, this process requires phosphorylation of MAP3K8/COT. Isoform 1 is less active in this respect. Promotes growth factor-independent proliferation by phosphorylation of cell cycle factors such as CDKN1A and CDKN1B. Involved in the positive regulation of chondrocyte survival and autophagy in the epiphyseal growth plate. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4X7Q) | 4X7Q |
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Go to ligands | 26.1100 5.1900 3.0400 | |
| D0398 | Cathepsin G | P08311 | CATG_HUMAN | CG | Cleaves complement C3. Has antibacterial activity against the Gram-negative bacterium P. aeruginosa, antibacterial activity is inhibited by LPS from P. aeruginosa, Z-Gly-Leu-Phe-CH2Cl and phenylmethylsulfonyl fluoride. Serine protease with trypsin- and chymotrypsin-like specificity. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['12 Diseases of the respiratory system'] | 1 | Downloaded from PDB (1T32) | 1T32 |
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Go to ligands | 14.5700 69.1300 2.7000 | |
| D0399 | Bromodomain-containing protein 2 | P25440 | BRD2_HUMAN | Really interesting new gene 3 protein, RING3, O27.1.1, KIAA9001 | Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly. May play a role in spermatogenesis or folliculogenesis. | Factors and Regulators | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5IG6) | 5IG6 |
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Go to ligands | 6.1000 15.2500 -5.7500 | |
| D0400 | Glutaminase | O94925+Q9UI32 | GLSK_HUMAN+GLSL_HUMAN | L-glutamine amidohydrolase, Glutaminase, mitochondrial, GLS | Plays a role in maintaining acid-base homeostasis. Regulates the levels of the neurotransmitter glutamate in the brain. Isoform 2 lacks catalytic activity. Catalyzes the first reaction in the primary pathway for the renal catabolism of glutamine. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (8BSK) | 8BSK |
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Go to ligands | -9.0800 6.5300 4.6400 | |
| D0401 | Aurora kinase A | O14965 | AURKA_HUMAN | hARK1, Serine/threonine-protein kinase aurora-A, Serine/threonine-protein kinase 6, Serine/threonine-protein kinase 15, Serine/threonine kinase 15, STK6, STK15, IAK1, Breast tumor-amplified kinase, BTAK, Aurora/IPL1-related kinase 1, Aurora-related kinase 1, Aurora-A, Aurora 2, AYK1, AURA, ARK1, ARK-1, AIRK1, AIK | Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis. Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '05 Endocrine, nutritional or metabolic diseases'] | 2 | Downloaded from PDB (5L8L) | 5L8L |
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Go to ligands | 8.2800 -3.6300 -15.1300 | |
| D0402 | N-formyl peptide receptor | P21462 | FPR1_HUMAN | N-formylpeptide chemoattractant receptor, FPR1, FPR | High affinity receptor for N-formyl-methionyl peptides (fMLP), which are powerful neutrophil chemotactic factors (PubMed:2161213, PubMed:2176894, PubMed:10514456, PubMed:15153520). Binding of fMLP to the receptor stimulates intracellular calcium mobilization and superoxide anion release (PubMed:2161213, PubMed:1712023, PubMed:15153520). This response is mediated via a G-protein that activates a phosphatidylinositol- calcium second messenger system(PubMed:1712023, PubMed:10514456). | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['13 Diseases of the digestive system'] | 1 | Downloaded from PDB (7VFX) | 7VFX |
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Go to ligands | 109.8300 116.8300 75.7000 | |
| D0403 | DNA [cytosine-5]-methyltransferase 1 | P26358 | DNMT1_HUMAN | MCMT, M.HsaI, Dnmt1, DNMT, DNA methyltransferase HsaI, DNA MTase HsaI, DNA (cytosine5)methyltransferase 1, DNA (cytosine-5)-methyltransferase 1, CXXCtype zinc finger protein 9, CXXC9, CXXC-type zinc finger protein 9, AIM | Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. Promotes tumor growth. Methylates CpG residues. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '03 Diseases of the blood or blood-forming organs'] | 2 | Downloaded from PDB (6X9J) | 6X9J |
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Go to ligands | -40.0000 -8.9300 27.5100 | |
| D0404 | Erbb2 tyrosine kinase receptor | P04626 | ERBB2_HUMAN | p185erbB2, Tyrosine kinase-type cell surface receptor HER2, Receptor tyrosine-protein kinase erbB-2, Proto-oncogene c-ErbB-2, Proto-oncogene Neu, NGL, NEU, Metastatic lymph node gene 19 protein, MLN19, MLN 19, HER2, CD340 | Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. | Enzyme | Transferase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms', '09 Diseases of the visual system'] | 2 | Downloaded from PDB (7PCD) | 7PCD |
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Go to ligands | 6.4500 -5.8900 -14.1600 | |
| D0405 | Oxalosuccinate decarboxylase | O75874 | IDHC_HUMAN | PICD, NADP(+)-specific ICDH, Isocitrate dehydrogenase [NADP] cytoplasmic, IDP, IDH, Cytosolic NADP-isocitrate dehydrogenase | Catalyses the NADPH-dependent reduction of alpha-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). | Enzyme | Oxidoreductase | Successful | ['02 Neoplasms'] | 1 | ['02 Neoplasms'] | 1 | Downloaded from PDB (4UMX) | 4UMX |
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Go to ligands | 13.1200 27.3600 82.5800 | |
| D0406 | Neuropeptide Y receptor type 1 | P25929 | NPY1R_HUMAN | Neuropeptide Y-Y1 receptor, Neuropeptide Y receptor Y1, Neuropeptide Y Y(1) receptor, NPY1R, NPY1-R | Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is NPY > [Pro-34] PYY, PYY and [Leu-31, Pro-34] NPY > NPY (2-36) > [Ile-31, Gln-34] PP and PYY (3-36) > PP > NPY free acid. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['05 Endocrine, nutritional or metabolic diseases', '06 Mental, behavioural or neurodevelopmental disorders'] | 2 | Downloaded from PDB (5ZBQ) | 5ZBQ |
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Go to ligands | -47.1500 -19.5200 71.4500 | |
| D0407 | C-C chemokine receptor type 2 | P41597 | CCR2_HUMAN | Monocyte chemoattractant protein 1 receptor, MCP-1-R, Chemokine receptor CCR2B, CMKBR2, CD192, CCR-2, CC-CKR-2, C-C CKR-2 | Its binding with CCL2 on monocytes and macrophages mediates chemotaxis and migration induction through the activation of the PI3K cascade, the small G protein Rac and lamellipodium protrusion. Also acts as a receptor for the beta-defensin DEFB106A/DEFB106B. Regulates the expression of T-cell inflammatory cytokines and T-cell differentiation, promoting the differentiation of T-cells into T-helper 17 cells (Th17) during inflammation. Faciltates the export of mature thymocytes by enhancing directional movement of thymocytes to sphingosine-1-phosphate stimulation and up-regulation of S1P1R expression, signals through the JAK-STAT pathway to regulate FOXO1 activity leading to an increased expression of S1P1R. Plays an important role in mediating peripheral nerve injury-induced neuropathic pain. Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B. Mediates the recruitment of macrophages and monocytes to the injury site following brain injury. Key functional receptor for CCL2 but can also bind CCL7 and CCL12. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms', '08 Diseases of the nervous system', '09 Diseases of the visual system', '12 Diseases of the respiratory system', '15 Diseases of the musculoskeletal system or connective tissue', '16 Diseases of the genitourinary system', '21 Symptoms, signs or clinical findings, not elsewhere classified'] | 8 | Downloaded from PDB (6GPX) | 6GPX |
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Go to ligands | 61.5300 -2.0600 51.8700 | |
| D0408 | Programmed cell death 1 ligand 1 | Q9NZQ7 | PD1L1_HUMAN | hPD-L1, Programmed death ligand 1, PDL1, PDCD1LG1, PDCD1L1, PDCD1 ligand 1, B7H1, B7-H1, B7 homolog 1 | As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response. Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10). Plays a critical role in induction and maintenance of immune tolerance to self. | Other | - | Successful | ['02 Neoplasms'] | 1 | ['01 Certain infectious or parasitic diseases', '02 Neoplasms'] | 2 | Downloaded from PDB (7NLD) | 7NLD |
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Go to ligands | 30.6600 1.9500 -27.6600 | |
| D0409 | Adenosine kinase | P55263 | ADK_HUMAN | Adenosine 5'-phosphotransferase, AK | Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides. ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['08 Diseases of the nervous system'] | 1 | Downloaded from PDB (2I6B) | 2I6B |
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Go to ligands | 5.3900 -3.1500 27.3800 | |
| D0410 | T-cell-specific kinase | Q08881 | ITK_HUMAN | Tyrosine kinase ITK, Inducible T cell kinase, EMT | Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3. Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '04 Diseases of the immune system', '14 Diseases of the skin'] | 3 | Downloaded from PDB (4M15) | 4M15 |
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Go to ligands | -3.6800 8.8900 15.5300 | |
| D0411 | Angiopoietin 1 receptor | Q02763 | TIE2_HUMAN | hTIE2, VMCM1, VMCM, Tyrosine-protein kinase receptor TIE-2, Tyrosine-protein kinase receptor TEK, Tyrosine kinase with Ig and EGF homology domains-2, Tunica interna endothelial cell kinase, TIE2, P140 TEK, Endothelial tyrosine kinase, Endothelial Cell-Specific Receptor TIE-2, CD202b antigen, CD202b | Has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1, SHC1 and TIE1. Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '09 Diseases of the visual system', '11 Diseases of the circulatory system'] | 3 | Downloaded from PDB (6MWE) | 6MWE |
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Go to ligands | -9.6800 33.1800 112.6400 | |
| D0412 | Lysophosphatidic acid receptor 1 | Q92633 | LPAR1_HUMAN | Lysophosphatidic acid receptor Edg-2, LPA1, LPA-1, LPA receptor 1, EDG2, EDG 2 receptor | Plays a role in the reorganization of the actin cytoskeleton, cell migration, differentiation and proliferation, and thereby contributes to the responses to tissue damage and infectious agents. Activates downstream signaling cascades via the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Signaling inhibits adenylyl cyclase activity and decreases cellular cAMP levels. Signaling triggers an increase of cytoplasmic Ca(2+) levels. Activates RALA, this leads to the activation of phospholipase C (PLC) and the formation of inositol 1,4,5-trisphosphate. Signaling mediates activation of down-stream MAP kinases. Contributes to the regulation of cell shape. Promotes Rho-dependent reorganization of the actin cytoskeleton in neuronal cells and neurite retraction. Promotes the activation of Rho and the formation of actin stress fibers. Promotes formation of lamellipodia at the leading edge of migrating cells via activation of RAC1. Through its function as lysophosphatidic acid receptor, plays a role in chemotaxis and cell migration, including responses to injury and wounding. Plays a role in triggering inflammation in response to bacterial lipopolysaccharide (LPS) via its interaction with CD14. Promotes cell proliferation in response to lysophosphatidic acid. Required for normal skeleton development. May play a role in osteoblast differentiation. Required for normal brain development. Required for normal proliferation, survival and maturation of newly formed neurons in the adult dentate gyrus. Plays a role in pain perception and in the initiation of neuropathic pain. Receptor for lysophosphatidic acid (LPA). | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['04 Diseases of the immune system', '12 Diseases of the respiratory system', '14 Diseases of the skin', '16 Diseases of the genitourinary system'] | 4 | Downloaded from PDB (4Z35) | 4Z35 |
|
Go to ligands | -1.9900 -27.0600 50.3500 | |
| D0413 | MALT lymphoma-associated translocation | Q9UDY8 | MALT1_HUMAN | MALT lymphoma-associated translocation, Paracaspase | Protease that enhances BCL10-induced activation of NF-kappa-B by mediating its cleavage. MALT1-dependent BCL10 cleavage plays an important role in T-cell antigen receptor-induced integrin adhesion. Involved in the induction of T helper 17 cells (Th17) differentiation. Cleaves RC3H1 and ZC3H12A in response to T-cell receptor (TCR) stimulation which releases their cooperatively repressed targets to promote Th17 cell differentiation (By similarity). Also mediates cleavage of N4BP1 in T-cells following TCR-mediated activation, leading to N4BP1 inactivation. Also has ubiquitin ligase activity: binds to TRAF6, inducing TRAF6 oligomerization and activation of its ligase activity. | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (7PAW) | 7PAW |
|
Go to ligands | 11.2600 4.6300 -5.1200 | |
| D0414 | Presenilin 1 | P49768 | PSN1_HUMAN | S182 protein, Protein S182, Presenilin-1, PSNL1, PS1, PS-1, AD3 | Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. Stimulates cell-cell adhesion via its interaction with CDH1, this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin). Under conditions of apoptosis or calcium influx, cleaves CDH1. This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling. Required for normal embryonic brain and skeleton development, and for normal angiogenesis. Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2. The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis. Involved in the regulation of neurite outgrowth. Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression. Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). | Enzyme | Hydrolase | Clinical trial | ['No approved drug'] | 0 | ['15 Diseases of the musculoskeletal system or connective tissue'] | 1 | Downloaded from PDB (7D8X) | 7D8X |
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Go to ligands | 166.0100 182.6100 170.7800 | |
| D0415 | Ribosomal protein S6 kinase beta-1 | P23443 | KS6B1_HUMAN | p70-S6K 1, p70 ribosomal S6 kinase alpha, p70 S6KA, p70 S6K-alpha, p70 S6 kinase alpha, Serine/threonine-protein kinase 14A, STK14A, S6K-beta-1, S6K, Ribosomal protein S6 kinase I, P70S6K1, P70-S6K, 70 kDa ribosomal protein S6 kinase 1 | Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin. Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR. Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition. Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms', '08 Diseases of the nervous system', '13 Diseases of the digestive system'] | 3 | Downloaded from PDB (3WF7) | 3WF7 |
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Go to ligands | 10.0300 -10.4300 9.8800 | |
| D0416 | TYRO3 tyrosine kinase receptor | Q06418 | TYRO3_HUMAN | Tyrosine-protein kinase receptor TYRO3, Tyrosine-protein kinase TIF, Tyrosine-protein kinase SKY, Tyrosine-protein kinase RSE, Tyrosine-protein kinase DTK, Tyrosine-protein kinase BYK, TIF, SKY, RSE, DTK, BYK | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. Activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes. TYRO3 signaling plays a role in various processes such as neuron protection from excitotoxic injury, platelet aggregation and cytoskeleton reorganization. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Modelled with AlphaFold (AF-Q06418-F1-model_v4) | Ab initio |
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Go to ligands | -17.2000 -3.8400 21.1000 | |
| D0417 | Melanocortin receptor 5 | P33032 | MC5R_HUMAN | MC5-R, MC2, MC-2 | The activity of this receptor is mediated by G proteins which activate adenylate cyclase. This receptor is a possible mediator of the immunomodulation properties of melanocortins. Receptor for MSH (alpha, beta and gamma) and ACTH. | Receptor | - | Clinical trial | ['No approved drug'] | 0 | ['14 Diseases of the skin'] | 1 | Modelled with SWISS-MODEL (7PIU.1.A) | Homology |
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Go to ligands | 109.0200 109.1600 146.1000 | |
| D0418 | Heat shock protein 90 beta | P08238 | HS90B_HUMAN | Heat shock 84 kDa, HSP84, HSP 84 | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:27295069, PubMed:26991466). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone that is involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). | Other | - | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (5UCJ) | 5UCJ |
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Go to ligands | -23.7500 100.7000 -0.6400 | |
| D0419 | Fatty acid synthase | P49327 | FAS_HUMAN | Yeast fatty acid synthase, Fatty-acyl-CoA synthase, Fatty acyl-CoA synthetase enzyme, FAS | Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities as an acyl carrier protein. | Enzyme | Transferase | Successful | ['21 Symptoms, signs or clinical findings, not elsewhere classified'] | 1 | ['02 Neoplasms', '13 Diseases of the digestive system'] | 2 | Downloaded from PDB (3HHD) | 3HHD |
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Go to ligands | -14.5000 58.1900 30.3200 | |
| D0420 | Leucine-rich repeat kinase 2 | Q5S007 | LRRK2_HUMAN | PARK8, Leucine-rich repeat serine/threonine-protein kinase 2, Dardarin | Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:20949042, PubMed:22012985, PubMed:26824392, PubMed:27830463, PubMed:29125462, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:30635421, PubMed:21850687, PubMed:23395371, PubMed:17114044, PubMed:24687852, PubMed:26014385, PubMed:25201882). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421, PubMed:23395371). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29212815). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421}. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['08 Diseases of the nervous system'] | 1 | Downloaded from PDB (6OJF) | 6OJF |
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Go to ligands | 16.0600 12.8700 50.3600 | |
| D0421 | MAPK signal-integrating kinase 1 | Q9BUB5 | MKNK1_HUMAN | Mnk1, MAP kinase signal-integrating kinase 1 | May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (2HW6) | 2HW6 |
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Go to ligands | 18.3200 51.5700 78.8800 | |
| D0422 | ATM serine/threonine kinase | Q13315 | ATM_HUMAN | Serine-protein kinase ATM, Ataxia telangiectasia mutated, A-T mutated | Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9, UBQLN4 and DCLRE1C. May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response. | Enzyme | Transferase | Clinical trial | ['No approved drug'] | 0 | ['02 Neoplasms'] | 1 | Downloaded from PDB (7NI4) | 7NI4 |
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Go to ligands | 189.5800 248.2300 157.1300 |
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