Target Information
Target General Infomation | |||||
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Target ID |
T17980
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Former ID |
TTDS00406
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Target Name |
Fyn tyrosine kinase
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Gene Name |
FYN
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Synonyms |
Protooncogene Syn; SLK; p59-Fyn; Proto-oncogene tyrosine-protein kinase Fyn; FYN
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Target Type |
Successful
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Disease | Chronic myelogenous leukaemia [ICD9: 205.1; ICD10: C92.1] | ||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Multiple myeloma [ICD9: 203; ICD10: C90] | |||||
Function |
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. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates withPTK2/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 cellsurvival 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 essentialpart of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL 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. Participatesin the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. 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.
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BioChemical Class |
Kinase
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Target Validation |
T17980
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UniProt ID | |||||
EC Number |
EC 2.7.10.2
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Sequence |
MGCVQCKDKEATKLTEERDGSLNQSSGYRYGTDPTPQHYPSFGVTSIPNYNNFHAAGGQG
LTVFGGVNSSSHTGTLRTRGGTGVTLFVALYDYEARTEDDLSFHKGEKFQILNSSEGDWW EARSLTTGETGYIPSNYVAPVDSIQAEEWYFGKLGRKDAERQLLSFGNPRGTFLIRESET TKGAYSLSIRDWDDMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLVQHYSERAAGLCC RLVVPCHKGMPRLTDLSVKTKDVWEIPRESLQLIKRLGNGQFGEVWMGTWNGNTKVAIKT LKPGTMSPESFLEEAQIMKKLKHDKLVQLYAVVSEEPIYIVTEYMNKGSLLDFLKDGEGR ALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIEDNEY TARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVE RGYRMPCPQDCPISLHELMIHCWKKDPEERPTFEYLQSFLEDYFTATEPQYQPGENL |
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Structure |
1A0N; 1AOT; 1AOU; 1AVZ; 1AZG; 1EFN; 1FYN; 1G83; 1M27; 1NYF; 1NYG; 1SHF; 1ZBJ; 2DQ7; 3H0F; 3H0H; 3H0I; 3UA6; 3UA7; 4D8D; 4EIK; 1A0N;1AOT; 1AOU; 1AVZ; 1AZG; 1EFN; 1FYN; 1G83; 1M27; 1NYF; 1NYG; 1SHF; 1ZBJ; 2DQ7; 3H0F; 3H0H; 3H0I; 3UA6; 3UA7; 4D8D; 4EIK
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Drugs and Mode of Action | |||||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Sphingolipid signaling pathway | ||||
Axon guidance | |||||
Osteoclast differentiation | |||||
Focal adhesion | |||||
Adherens junction | |||||
Platelet activation | |||||
Natural killer cell mediated cytotoxicity | |||||
T cell receptor signaling pathway | |||||
Fc epsilon RI signaling pathway | |||||
Cholinergic synapse | |||||
Prion diseases | |||||
Pathogenic Escherichia coli infection | |||||
Measles | |||||
Viral myocarditis | |||||
NetPath Pathway | TSH Signaling Pathway | ||||
IL2 Signaling Pathway | |||||
TGF_beta_Receptor Signaling Pathway | |||||
PANTHER Pathway | Axon guidance mediated by semaphorins | ||||
Cadherin signaling pathway | |||||
Integrin signalling pathway | |||||
Parkinson disease | |||||
Pathway Interaction Database | Fc-epsilon receptor I signaling in mast cells | ||||
ErbB4 signaling events | |||||
Glypican 1 network | |||||
TCR signaling in na& | |||||
#xef | |||||
ve CD4+ T cells | |||||
Signaling events mediated by PTP1B | |||||
Ephrin A reverse signaling | |||||
Reelin signaling pathway | |||||
Regulation of p38-alpha and p38-beta | |||||
TCR signaling in na& | |||||
ve CD8+ T cells | |||||
Angiopoietin receptor Tie2-mediated signaling | |||||
Thromboxane A2 receptor signaling | |||||
Netrin-mediated signaling events | |||||
IL2-mediated signaling events | |||||
CXCR4-mediated signaling events | |||||
Class I PI3K signaling events | |||||
Posttranslational regulation of adherens junction stability and dissassembly | |||||
amb2 Integrin signaling | |||||
EPHA forward signaling | |||||
E-cadherin signaling in keratinocytes | |||||
PDGFR-beta signaling pathway | |||||
Nephrin/Neph1 signaling in the kidney podocyte | |||||
Signaling events mediated by VEGFR1 and VEGFR2 | |||||
Syndecan-3-mediated signaling events | |||||
Ephrin B reverse signaling | |||||
Alpha-synuclein signaling | |||||
Signaling events mediated by focal adhesion kinase | |||||
PathWhiz Pathway | Fc Epsilon Receptor I Signaling in Mast Cells | ||||
Reactome | GPVI-mediated activation cascade | ||||
PIP3 activates AKT signaling | |||||
Regulation of KIT signaling | |||||
Cell surface interactions at the vascular wall | |||||
FCGR activation | |||||
PECAM1 interactions | |||||
Constitutive Signaling by Aberrant PI3K in Cancer | |||||
DAP12 signaling | |||||
EPH-Ephrin signaling | |||||
Role of LAT2/NTAL/LAB on calcium mobilization | |||||
Nephrin interactions | |||||
NCAM signaling for neurite out-growth | |||||
CD28 co-stimulation | |||||
CD28 dependent PI3K/Akt signaling | |||||
CD28 dependent Vav1 pathway | |||||
CTLA4 inhibitory signaling | |||||
EPHB-mediated forward signaling | |||||
EPHA-mediated growth cone collapse | |||||
EPH-ephrin mediated repulsion of cells | |||||
CRMPs in Sema3A signaling | |||||
DCC mediated attractive signaling | |||||
Netrin mediated repulsion signals | |||||
VEGFA-VEGFR2 Pathway | |||||
Dectin-2 family | |||||
CD209 (DC-SIGN) signaling | |||||
RAF/MAP kinase cascade | |||||
Platelet Adhesion to exposed collagen | |||||
Regulation of signaling by CBL | |||||
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers | |||||
WikiPathways | TCR Signaling Pathway | ||||
Interferon type I signaling pathways | |||||
IL-2 Signaling Pathway | |||||
Kit receptor signaling pathway | |||||
IL-3 Signaling Pathway | |||||
Ectoderm Differentiation | |||||
Fc epsilon receptor (FCERI) signaling | |||||
Signaling by the B Cell Receptor (BCR) | |||||
Signaling by SCF-KIT | |||||
DAP12 interactions | |||||
Host Interactions of HIV factors | |||||
PIP3 activates AKT signaling | |||||
T-Cell Receptor and Co-stimulatory Signaling | |||||
Primary Focal Segmental Glomerulosclerosis FSGS | |||||
BDNF signaling pathway | |||||
Interleukin-11 Signaling Pathway | |||||
B Cell Receptor Signaling Pathway | |||||
Pathogenic Escherichia coli infection | |||||
TSLP Signaling Pathway | |||||
IL-7 Signaling Pathway | |||||
Leptin signaling pathway | |||||
Semaphorin interactions | |||||
Platelet Adhesion to exposed collagen | |||||
Netrin-1 signaling | |||||
Nephrin interactions | |||||
NCAM signaling for neurite out-growth | |||||
Integrin-mediated Cell Adhesion | |||||
GPVI-mediated activation cascade | |||||
Costimulation by the CD28 family | |||||
Cell surface interactions at the vascular wall | |||||
References | |||||
Ref 522319 | ClinicalTrials.gov (NCT00676299) A Safety and Dose-finding Study of JNJ-26483327, a Drug in Development for Cancer, for Patients With Advanced and/or Refractory Solid Malignancies.. U.S. National Institutes of Health. | ||||
Ref 536577 | Dasatinib: a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia. Clin Ther. 2007 Nov;29(11):2289-308. | ||||
Ref 536957 | Current and future treatments of bone metastases. Expert Opin Emerg Drugs. 2008 Dec;13(4):609-27. | ||||
Ref 527295 | Discovery of novel 2-(aminoheteroaryl)-thiazole-5-carboxamides as potent and orally active Src-family kinase p56(Lck) inhibitors. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6061-6. | ||||
Ref 527932 | J Med Chem. 2005 Dec 29;48(26):8163-73.(6,7-Dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamines: platelet-derived growth factor receptor tyrosine kinase inhibitors with broad antiproliferative activity against tumor cells. | ||||
Ref 528018 | Bioorg Med Chem Lett. 2006 Apr 1;16(7):1950-3. Epub 2006 Feb 3.Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis. | ||||
Ref 529647 | J Med Chem. 2008 Sep 25;51(18):5680-9. Epub 2008 Aug 21.Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models. | ||||
Ref 536331 | Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42. Epub 2006 Nov 28. | ||||
Ref 536474 | A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22. |
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