Tyrosine-protein kinase Yes

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 receptor tyrosine kinases (RTKs) including EGFR, 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. Catalyzes phosphorylation of organic cation transporter OCT2 which induces its transport activity.

Classification

Family (Pfam)

PF07714 PK_Tyr_Ser-Thr, PF00017 SH2, PF00018 SH3_1

InterPro

Kinase-like_dom_sf, Non-receptor_tyrosine_kinases, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser-Thr/Tyr_kinase_cat_dom, SH2, SH2_dom_sf, SH3-like_dom_sf, SH3_domain, Tyr_kinase_AS, Tyr_kinase_cat_dom, Yes_SH3

Functional cluster

Protein Serine/Threonine Kinases

Experimental structures · PDB · 1

• 2HDA X-ray 1.90A

A predicted model is available from AlphaFold.

Gene Ontology · 23

• GO:0005884 actin filament
• GO:0005813 centrosome
• GO:0005829 cytosol
• GO:0070062 extracellular exosome
• GO:0005925 focal adhesion
• GO:0005794 Golgi apparatus
• GO:0005886 plasma membrane
• GO:0005524 ATP binding
• GO:0019899 enzyme binding
• GO:0004715 non-membrane spanning protein tyrosine kinase activity
• GO:0001784 phosphotyrosine residue binding
• GO:0004713 protein tyrosine kinase activity
• GO:0005102 signaling receptor binding
• GO:0044325 transmembrane transporter binding
• GO:0030154 cell differentiation
• GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
• GO:0048013 ephrin receptor signaling pathway
• GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
• GO:0050900 leukocyte migration
• GO:0002862 negative regulation of inflammatory response to antigenic stimulus
• GO:0036211 protein modification process
• GO:0043114 regulation of vascular permeability
• GO:0031295 T cell costimulation

Drugs targeting this protein · 6

• DASATINIB ANHYDROUS inhibitor
• ILORASERTIB inhibitor
• JNJ-26483327 inhibitor
• XL-228 inhibitor
• TG100-801 inhibitor
• ENMD-981693 inhibitor

Related proteins · sequence + function similarity

• Tyrosine-protein kinase Yes 1.00
• Tyrosine-protein kinase Yes 0.99
• Tyrosine-protein kinase Yes 0.99
• Tyrosine-protein kinase Yes 0.99
• Tyrosine-protein kinase yes 0.99
• Tyrosine-protein kinase Yes 0.99
• Tyrosine-protein kinase Yes 0.99
• Tyrosine-protein kinase transforming protein Yes 0.98
• Tyrosine-protein kinase fynb 0.96
• Tyrosine-protein kinase Fyn 0.96
• Tyrosine-protein kinase Fyn 0.96
• Tyrosine-protein kinase Fyn 0.96

Co-cited proteins · studied together in the literature

• Membrane cofactor protein 1 shared papers
• Tyrosine-protein kinase CSK 1 shared papers
• Proto-oncogene tyrosine-protein kinase LCK 1 shared papers
• Tyrosine-protein kinase Yes 1 shared papers
• Catenin beta-1 1 shared papers
• Transcriptional coactivator YAP1 1 shared papers
• Tyrosine-protein kinase Fyn 1 shared papers
• Protein scribble homolog 1 shared papers
• Solute carrier family 22 member 2 1 shared papers
• Tyrosine-protein kinase Yes 1 shared papers
• Interleukin-6 receptor subunit beta 1 shared papers
• Interleukin-6 1 shared papers

Literature · 24 cited papers

• Scribble sub-cellular localization modulates recruitment of YES1 to regulate YAP1 phosphorylation. Cell Chem. Biol. · 2021
• A phosphotyrosine switch regulates organic cation transporters. Nat. Commun. · 2016
• A gp130-Src-YAP module links inflammation to epithelial regeneration. Nature · 2015
• The naturally processed CD95L elicits a c-yes/calcium/PI3K-driven cell migration pathway. PLoS Biol. · 2011
• Clues for c-Yes involvement in the cell cycle and cytokinesis. Cell Cycle · 2011
• Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening. BMC Immunol. · 2009
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• Phosphorylation of collapsin response mediator protein 2 on Tyr-479 regulates CXCL12-induced T lymphocyte migration. J. Biol. Chem. · 2009
• Differential trafficking of Src, Lyn, Yes and Fyn is specified by the state of palmitoylation in the SH4 domain. J. Cell Sci. · 2009
• Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• Phosphorylation of cyclin dependent kinase 4 on tyrosine 17 is mediated by Src family kinases. FEBS J. · 2008
• … and 12 more in the literature graph