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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
General
phosphoprotein
RNA-binding protein
Properties
SIZE: entity length = 870 aa
MW = 93 kD
COMPARTMENT: cytoplasm
MOTIF: src homology 3 [SH3] domain
SITE: 3-65
proline-rich region
SITE: 74-87
MOTIF: proline residue (SEVERAL)
Substrate for kinases {115-416}
MOTIF: Tyr phosphorylation site {Y128}
Ser phosphorylation site {S134}
Ser phosphorylation site {S139}
Tyr phosphorylation site {Y222}
Tyr phosphorylation site {Y224}
Tyr phosphorylation site {Y234}
Tyr phosphorylation site {Y249}
Thr phosphorylation site {T269}
Ser phosphorylation site {S292}
Tyr phosphorylation site {Y327}
Tyr phosphorylation site {Y362}
Tyr phosphorylation site {Y387}
Tyr phosphorylation site {Y410}
serine-rich region {422-614}
MOTIF: serine residue (SEVERAL)
peptide motif {635-643}
MOTIF: Ser phosphorylation site {S639}
Divergent helix-loop-helix motif {746-796}
References
- UniProt :accession P56945
- Pawson T.
Protein modules and signalling networks.
Nature. 1995 Feb 16;373(6515):573-80. Review.
PMID: 7531822
Databases & Figures
OMIM 602941
UniProt P56945
PFAM correlations
Entrez Gene 9564
Kegg hsa:9564
E-cadherin/CD31 ... F-actin