Function: Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion. Implicated in induction of cell migration. Overexpression confers antiestrogen resistance on breast cancer cells. Ref.10 Ref.11
Subunit structure: Forms complexes in vivo with PTK2/FAK1, adapter protein CRKL and LYN kinase. Can heterodimerize with NEDD9. Interacts with BCAR3, the interaction regulates adhesion-dependent serine phosphorylation. Interacts with NPHP1 and SH2D3C. Interacts with activated CSPG4. Interacts with BMX, INPPL1/SHIP2 and PEAK1. Part of a collagen-stimulated complex involved in cell migration made of CDC42, CRK, TNK2 and BCAR1/p130cas. Interacts with TNK2 via SH3 domains. Interacts with PTK2B/PYK2. Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.16
Subcellular location: Cell junction › focal adhesion. Cytoplasm. Note: Unphosphorylated form localizes in the cytoplasm and can move to the membrane upon tyrosine phosphorylation
By similarity. Ref.10
Tissue specificity: Widely expressed with an abundant expression in the testis. Low level of expression seen in the liver, thymus, and peripheral blood leukocytes. The protein has been detected in a B-cell line.
Domain: Contains a central domain (substrate domain) containing multiple potential SH2-binding sites and a C-terminal domain containing a divergent helix-loop-helix (HLH) motif. The SH2-binding sites putatively bind CRK, NCK and ABL1 SH2 domains. The HLH motif is absolutely required for the induction of pseudohyphal growth in yeast and mediates heterodimerization with NEDD9
By similarity.A serine-rich region promotes activation of the serum response element (SRE).The SH3 domain is necessary for the localization of the protein to focal adhesions and interacts with one proline-rich region of PTK2/FAK11.
Post-translational modification: PTK2/FAK1 activation mediates phosphorylation at the YDYVHL motif; phosphorylation is most likely catalyzed by SRC family members. SRC-family kinases are recruited to the phosphorylated sites and can phosphorylate other tyrosine residues. Tyrosine phosphorylation is triggered by integrin-mediated adhesion of cells to the extracellular matrix. Ref.10 Ref.13 Ref.15 Ref.20Dephosphorylated by PTPN14 at Tyr-128. Ref.10 Ref.13 Ref.15 Ref.20
Sequence similarities: Belongs to the CAS family.Contains 1 SH3 domain.
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