Target General Infomation
Target ID
T17980
Former ID
TTDS00406
Target Name
Fyn tyrosine kinase
Gene Name
FYN
Synonyms
Protooncogene Syn; SLK; p59-Fyn; Proto-oncogene tyrosine-protein kinase Fyn; FYN
Target Type
Successful
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.
BioChemical Class
Kinase
Target Validation
T17980
UniProt ID
EC Number
EC 2.7.10.2
Sequence
MGCVQCKDKEATKLTEERDGSLNQSSGYRYGTDPTPQHYPSFGVTSIPNYNNFHAAGGQG
LTVFGGVNSSSHTGTLRTRGGTGVTLFVALYDYEARTEDDLSFHKGEKFQILNSSEGDWW
EARSLTTGETGYIPSNYVAPVDSIQAEEWYFGKLGRKDAERQLLSFGNPRGTFLIRESET
TKGAYSLSIRDWDDMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLVQHYSERAAGLCC
RLVVPCHKGMPRLTDLSVKTKDVWEIPRESLQLIKRLGNGQFGEVWMGTWNGNTKVAIKT
LKPGTMSPESFLEEAQIMKKLKHDKLVQLYAVVSEEPIYIVTEYMNKGSLLDFLKDGEGR
ALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIEDNEY
TARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVE
RGYRMPCPQDCPISLHELMIHCWKKDPEERPTFEYLQSFLEDYFTATEPQYQPGENL
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
Drugs and Mode of Action
Drug(s) Dasatinib Drug Info Approved Chronic myelogenous leukaemia [528715], [536577], [541021], [551871]
Dasatinib Drug Info Phase 2 Multiple myeloma [536957], [541021]
JNJ-26483327 Drug Info Phase 1 Cancer [522319]
Inhibitor 1-Methoxy-2-[2-(2-Methoxy-Ethoxy]-Ethane Drug Info [551393]
CEP-5104 Drug Info [529647]
CEP-6331 Drug Info [529647]
compound 2 Drug Info [527295]
Dasatinib Drug Info [536331], [536474], [536797]
JNJ-10198409 Drug Info [527932]
JNJ-26483327 Drug Info [550423]
Ro-4396686 Drug Info [528018]
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&amp
#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&amp
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 522319ClinicalTrials.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 5287152006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
Ref 536577Dasatinib: 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 536957Current and future treatments of bone metastases. Expert Opin Emerg Drugs. 2008 Dec;13(4):609-27.
Ref 541021(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5678).
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 527295Discovery 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 527932J 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 528018Bioorg 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 529647J 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 536331Multi-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 536474A 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.
Ref 536797In vitro and clinical investigation of the relationship between CCR5 receptor occupancy and anti-HIV activity of Aplaviroc. J Clin Pharmacol. 2008 Oct;48(10):1179-88. Epub 2008 Aug 1.
Ref 550423National Cancer Institute Drug Dictionary (drug id 596693).
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.