{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P56945","secondaryAccessions":["B3KWD7","B4DEV4","B4DGB5","B4DIW5","B7Z7X7","E9PCL5","E9PCV2","F5GXA2","F5GXV6","F5H7Z0","F8WA69","Q6QEF7"],"uniProtkbId":"BCAR1_HUMAN","entryAudit":{"firstPublicDate":"2000-05-30","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2010-02-09","entryVersion":229,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Breast cancer anti-estrogen resistance protein 1"}},"alternativeNames":[{"fullName":{"value":"CRK-associated substrate"}},{"fullName":{"value":"Cas scaffolding protein family member 1"}},{"fullName":{"value":"p130cas"}}]},"genes":[{"geneName":{"value":"BCAR1"},"synonyms":[{"value":"CAS"},{"value":"CASS1"},{"value":"CRKAS"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61140"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12432078"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12832404"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17038317"}],"value":"Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion (PubMed:12432078, PubMed:12832404). Implicated in induction of cell migration and cell branching (PubMed:12432078, PubMed:12832404, PubMed:17038317). Involved in the BCAR3-mediated inhibition of TGFB signaling (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61140"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10502414"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10587647"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11158326"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12432078"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12832404"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17038317"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17174122"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19086031"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19454314"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20534451"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20798394"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22081014"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22801373"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9020138"}],"value":"Forms complexes in vivo with PTK2/FAK1, adapter protein CRKL and LYN kinase (PubMed:9020138). Heterodimerizes with NEDD9 (PubMed:10502414). Component of a complex comprised of SH2D3C, BCAR1/CAS, and CRK (PubMed:12432078). Within the complex, interacts with SH2D3C (via C-terminus), and CRK (PubMed:12432078, PubMed:17174122). Part of a complex comprised of PTPRA, BCAR1, BCAR3 (via SH2 domain) and SRC; the formation of the complex is dependent on integrin mediated-tyrosine phosphorylation of PTPRA (PubMed:22801373). Interacts with BCAR3 (via Ras-GEF domain); the interaction regulates adhesion-dependent serine phosphorylation (PubMed:22081014). Interacts with SMAD2 and SMAD3 (By similarity). Interacts with NPHP1 (By similarity). Interacts with PTK2B/PYK2 (PubMed:19086031, PubMed:9020138). Interacts (via C-terminus) with SH2D3C/CHAT isoform 2 (via C-terminus) (PubMed:17174122, PubMed:22081014). 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 (when tyrosine-phosphorylated) with tensin TNS1; the interaction is increased by phosphorylation of TNS1 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Localizes to focal adhesion sites following integrin engagement (By similarity)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12832404"}],"value":"Cell junction, focal adhesion","id":"SL-0118"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12832404"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61140"}],"value":"Cell projection, axon","id":"SL-0279"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["P56945-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["P56945-2"],"sequenceIds":["VSP_043559"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["P56945-3"],"sequenceIds":["VSP_045355"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["P56945-4"],"sequenceIds":["VSP_046127","VSP_046128"],"isoformSequenceStatus":"Described"},{"name":{"value":"5"},"isoformIds":["P56945-5"],"sequenceIds":["VSP_046748"],"isoformSequenceStatus":"Described"},{"name":{"value":"6"},"isoformIds":["P56945-6"],"sequenceIds":["VSP_046749"],"isoformSequenceStatus":"Described"},{"name":{"value":"7"},"isoformIds":["P56945-7"],"sequenceIds":["VSP_046750"],"isoformSequenceStatus":"Described"},{"name":{"value":"8"},"isoformIds":["P56945-8"],"sequenceIds":["VSP_046751"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10639512"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9020138"}],"value":"Expressed in B-cells (at protein level) (PubMed:9020138). Widely expressed with an abundant expression in the testis (PubMed:10639512). Low level of expression seen in the liver, thymus, and peripheral blood leukocytes (PubMed:10639512)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"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)"}],"commentType":"DOMAIN"},{"texts":[{"value":"A serine-rich region promotes activation of the serum response element (SRE)"}],"commentType":"DOMAIN"},{"texts":[{"value":"The SH3 domain is necessary for the localization of the protein to focal adhesions and interacts with one proline-rich region of PTK2/FAK11"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12832404"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19147981"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19454314"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22710723"}],"value":"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"}],"commentType":"PTM"},{"texts":[{"value":"Dephosphorylated by PTPN14 at Tyr-128"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19086031"}],"value":"Phosphorylated by SRC kinase in a EDN1- and PTK2B-mediated manner; phosphorylation strengthens its interaction with BCAR3 as part of the PTK2B/BCAR1/BCAR3/RAP1 signaling pathway"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the CAS family"}],"commentType":"SIMILARITY"},{"commentType":"WEB RESOURCE","resourceName":"Atlas of Genetics and Cytogenetics in Oncology and Haematology","resourceUrl":"https://atlasgeneticsoncology.org/gene/761/BCAR1","ftp":false}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":870,"modifier":"EXACT"}},"description":"Breast cancer anti-estrogen resistance 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