breast cancer anti-estrogen resistance protein 1; CRK-associated substrate; p130cas; Cas scaffolding protein family member 1 (BCAR1, CAS, CASS1, CRKAS)

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
• focal adhesion kinase 1 phosphorylates the protein at the YDYVHL motif
• SRC-family kinases are recruited to the phosphorylated sites & can phosphorylate other Tyr residues Tyr phosphorylation is triggered by integrin mediated adhesion of cells to the extracellular matrix forms complexes in vivo with focal adhesion kinase 1, adapter protein CRKL & LYN kinase
• can heterodimerize with CASL
• interacts with BCAR3, NPHP1, PTK2B & SH2D3C (putative)
• interacts with activated CSPG4
• interacts with INPPL1/SHIP2

Structure

• contains a central domain (substrate domain) containing multiple potential SH2-binding sites & a C-terminal domain containing a divergent helix-loop-helix (HLH) motif
• the SH2-binding sites putatively bind CRK, NCK & ABL SH2 domains
• the HLH motif is absolutely required for the induction of pseudohyphal growth in yeast & mediates heterodimerization with CASL
• 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 & interacts with one proline-rich region of focal adhesion kinase 1
• belongs to the CAS family
• contains 1 SH3 domain

Compartment

• cell junction, focal adhesion
• cytoplasm (putative)
• unphosphorylated form localizes in the cytoplasm & can move to the membrane upon Tyr phosphorylation (putative)

Expression

• widely expressed
• abundant expression in the testis
• low level of expression seen in the liver, thymus, & peripheral blood leukocytes
• the protein has been detected in a B-cell line

More general terms

• phosphoprotein
• RNA-binding protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9564
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:9564
• OMIM: https://mirror.omim.org/entry/602941
• UniProt: http://www.uniprot.org/uniprot/P56945.html