Target General Infomation
Target ID
T75570
Former ID
TTDS00408
Target Name
Proto-oncogene tyrosine-protein kinase Yes
Gene Name
YES1
Synonyms
FYN; Protooncogene Syn; SLK; p59-Fyn; YES1
Target Type
Clinical Trial
Disease Cancer [ICD9: 140-229; ICD10: C00-C96]
Function
Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptortyrosine kinases (RTKs) including EGRF, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. Upon EGFR activation, promotes the phosphorylation of PARD3 to favor epithelial tight junction assembly. Participates in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. Participates in CD95L/FASLG signaling pathway and mediates AKT-mediated cell migration. Plays a role in cell cycle progression by phosphorylating the cyclin-dependent kinase 4/CDK4 thus regulating the G1 phase. Also involved in G2/M progression and cytokinesis.
BioChemical Class
Kinase
Target Validation
T75570
UniProt ID
EC Number
EC 2.7.10.2
Sequence
MGCIKSKENKSPAIKYRPENTPEPVSTSVSHYGAEPTTVSPCPSSSAKGTAVNFSSLSMT
PFGGSSGVTPFGGASSSFSVVPSSYPAGLTGGVTIFVALYDYEARTTEDLSFKKGERFQI
INNTEGDWWEARSIATGKNGYIPSNYVAPADSIQAEEWYFGKMGRKDAERLLLNPGNQRG
IFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTLQKLVKHY
TEHADGLCHKLTTVCPTVKPQTQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTT
KVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMSKGSLLDFL
KEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARL
IEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILQTELVTKGRVPYPGMVNRE
VLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLEDYFTATEPQYQPG
ENL
Drugs and Mode of Action
Drug(s) JNJ-26483327 Drug Info Phase 1 Cancer [522319]
Inhibitor JNJ-26483327 Drug Info [550422]
TG-100435 Drug Info [528527]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Adherens junction
Tight junction
NetPath Pathway IL5 Signaling Pathway
IL2 Signaling Pathway
PANTHER Pathway Cadherin signaling pathway
Parkinson disease
CCKR signaling map ST
Pathway Interaction Database Noncanonical Wnt signaling pathway
Glypican 1 network
Signaling events mediated by PTP1B
Regulation of p38-alpha and p38-beta
CDC42 signaling events
Thromboxane A2 receptor signaling
Netrin-mediated signaling events
CXCR4-mediated signaling events
Class I PI3K signaling events
amb2 Integrin signaling
EPHA forward signaling
PDGFR-beta signaling pathway
Ephrin B reverse signaling
Alpha-synuclein signaling
Signaling events mediated by focal adhesion kinase
Reactome Regulation of KIT signaling
FCGR activation
PECAM1 interactions
EPH-Ephrin signaling
CD28 co-stimulation
CTLA4 inhibitory signaling
EPHB-mediated forward signaling
EPHA-mediated growth cone collapse
EPH-ephrin mediated repulsion of cells
Regulation of signaling by CBL
WikiPathways Signaling by SCF-KIT
Interleukin-11 Signaling Pathway
TSLP Signaling Pathway
Costimulation by the CD28 family
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 528527Bioorg Med Chem Lett. 2007 Feb 1;17(3):602-8. Epub 2006 Nov 7.Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinase inhibitor with anti-tumor activity in preclinical assays.
Ref 550422National Cancer Institute Drug Dictionary (drug id 596693).

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