BCAR1 (breast cancer anti-estrogen resistance 1)
2011-12-01 Allison Berrier   AffiliationDepartment of Oral, Craniofacial Biology, LSUHSC-NO School of Dentistry, 1100 Florida Avenue, Clinical Bldg, Room 8301, New Orleans, LA 70119, USA
Identity
DNA/RNA

Proteins
Note
Isoform 1: 916 aa, calc MW= 97,7 kDa. Isoform 2: 888 aa, (alternate 5 sequence compared to variant 1) calc MW= 95,1 kDa. Isoform 3: 888 aa, (alternate 5 sequence compared to variant 1) calc MW= 95,3 kDa. Isoform 4: 888 aa, (alternate 5 sequence and alternate splice site in the substrate domain compared to variant 1 resulting in a different N-terminus and additional segment in the middle region compared to isoform 1) calc MW= 95,3 kDa. Isoform 5: 870 aa, (lacks an exon in the 5 region, alternate AUG start codon, has a different N-terminus compared to isoform 1) calc MW= 93,16 kDa. Isoform 6: 870 aa, (different N-terminus compared to isoform 1) calc MW= 93,2 kDa. Isoform 7, 868 aa (shorter, alternate 5 sequence, different N-terminus compared to isoform 1) calc MW= 93 kDa. Isoform 8, 722 aa, (alternate internal sequence compared to isoform 1, different N-terminus compared to isoform 1) calc MW= 77,6 kDa. Isoform 9: 660 aa, (shorter alternate 5 sequence, different N-terminus compared to isoform 1) calc MW= 70,7 kDa.
BCAR proteins migrate during SDS-PAGE electrophoresis at a significantly higher molecular weight than predicted from sequence analysis perhaps due to the extensive phosphorylation of BCAR proteins. Calculated MW 93,2 kDa, SDS-PAGE observed MW 130 kDa. Potential sites of human BCAR1 phosphorylation (PhosphoSitePlus): tyrosine residues aa 12, 128, 165, 192, 222, 224, 234, 249, 267, 287, 306, 327, 362, 372, 387, 410, 653, 664, 666; serine residues aa 134, 139, 292, 437, 639; and threonine residues aa 269, 326, 385. Inducers of BCAR1 phosphorylation include cell matrix adhesion, extracellular matrix rigidity, growth factors, hormones and progression through the cell cycle. Phosphorylation of BCAR1 regulates BCAR1 dependent activities through altering protein interactions, protein localization and signaling cascades (Tikhmyanova et al., 2010).

Description
BCAR1 interacting proteins (BioGRID)
CRKII, p60-Src, PTPN12, PTK2 (FAK), RapGEF1 (C3G), NPHP1, PTPN1 (PTP1B), FES, SHIP2 (INPPL1), ARHGAP32 (p250GAP), Pyk2 (PTK2B), Fyn, CRKL, YWHAZ, SrcIN1 (SNIP), p85-alpha (PI3KR1), c-ABL (bcr/abl), Lyn, Grb2, Dock1, paxillin, TRIP6, SH-PTP2, ID2A, UHRF2, NEDD9, NCK1, VCL, SAP1, Zyxin, BCAR3 (AND-34), CD2AP, LCK, SFN, SH2D3C, JNK/SAPK1, SH3KBP1, tensin 1 (TNS1), HCK, EFS, E2F2, VPS11, HspA5, TUBA1A, GADD34, p140Cap, BCAR1 (p130CAS), PTP-PEST, CIZ, Aurora-A, 14-3-3, CHAT-H, AIP4, APC/C and CDH1.
Expression
Localisation
Function

Homology
Mutations
Somatic
Implicated in
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16105984 | 2005 | p130Cas mediates the transforming properties of the anaplastic lymphoma kinase. | Ambrogio C et al |
| 8995252 | 1997 | The related adhesion focal tyrosine kinase is tyrosine-phosphorylated after beta1-integrin stimulation in B cells and binds to p130cas. | Astier A et al |
| 18198129 | 2008 | Tac-beta1 inhibits FAK activation and Src signaling. | Berrier AL et al |
| 15972849 | 2005 | Crk-associated substrate tyrosine phosphorylation sites are critical for invasion and metastasis of SRC-transformed cells. | Brábek J et al |
| 15795225 | 2005 | The serine-rich domain from Crk-associated substrate (p130cas) is a four-helix bundle. | Briknarová K et al |
| 10639512 | 2000 | BCAR1, a human homologue of the adapter protein p130Cas, and antiestrogen resistance in breast cancer cells. | Brinkman A et al |
| 8649789 | 1996 | The identification of p130cas-binding proteins and their role in cellular transformation. | Burnham MR et al |
| 20505116 | 2010 | p130Cas is an essential transducer element in ErbB2 transformation. | Cabodi S et al |
| 21102636 | 2010 | Integrin signalling adaptors: not only figurants in the cancer story. | Cabodi S et al |
| 14583477 | 2003 | AND-34/BCAR3, a GDP exchange factor whose overexpression confers antiestrogen resistance, activates Rac, PAK1, and the cyclin D1 promoter. | Cai D et al |
| 16353145 | 2006 | Celecoxib induces anoikis in human colon carcinoma cells associated with the deregulation of focal adhesions and nuclear translocation of p130Cas. | Casanova I et al |
| 12542470 | 2003 | Interaction between the Yersinia protein tyrosine phosphatase YopH and eukaryotic Cas/Fyb is an important virulence mechanism. | Deleuil F et al |
| 21469768 | 2011 | Breast cancer anti-estrogen resistance protein 1 (BCAR1/p130cas) in pulmonary disease tissue and serum. | Deng B et al |
| 21994904 | 2011 | The adaptor proteins p140CAP and p130CAS as molecular hubs in cell migration and invasion of cancer cells. | Di Stefano P et al |
| 10739664 | 2000 | Crk-associated substrate p130(Cas) interacts with nephrocystin and both proteins localize to cell-cell contacts of polarized epithelial cells. | Donaldson JC et al |
| 15448007 | 2004 | The prognostic value of BCAR1 in patients with primary breast cancer. | Dorssers LC et al |
| 21720550 | 2011 | Carcinoma matrix controls resistance to cisplatin through talin regulation of NF-kB. | Eberle KE et al |
| 21346785 | 2011 | The integrin signalling adaptor p130CAS is also a key player in prostate cancer. | Fromont G et al |
| 17192874 | 2007 | BCAR1 expression in prostate cancer: association with 16q23 LOH status, tumor progression and EGFR/KAI1 staining. | Fromont G et al |
| 10896938 | 2000 | p130Cas regulates the activity of AND-34, a novel Ral, Rap1, and R-Ras guanine nucleotide exchange factor. | Gotoh T et al |
| 18842495 | 2008 | Relation among p130Cas, E-cadherin and beta-catenin expression, clinicopathologic significance and prognosis in human hepatocellular carcinoma. | Guo C et al |
| 10502464 | 1999 | YopH dephosphorylates Cas and Fyn-binding protein in macrophages. | Hamid N et al |
| 8662921 | 1996 | p130Cas, a substrate associated with v-Src and v-Crk, localizes to focal adhesions and binds to focal adhesion kinase. | Harte MT et al |
| 9697697 | 1998 | Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas. | Honda H et al |
| 8700507 | 1996 | Networks of interaction of p120cbl and p130cas with Crk and Grb2 adaptor proteins. | Khwaja A et al |
| 14660614 | 2004 | The 31-kDa caspase-generated cleavage product of p130cas functions as a transcriptional repressor of E2A in apoptotic cells. | Kim W et al |
| 9472046 | 1998 | CAS/Crk coupling serves as a "molecular switch" for induction of cell migration. | Klemke RL et al |
| 10799562 | 2000 | Association of p130CAS with phosphatidylinositol-3-OH kinase mediates adenovirus cell entry. | Li E et al |
| 10669742 | 2000 | CIZ, a zinc finger protein that interacts with p130(cas) and activates the expression of matrix metalloproteinases. | Nakamoto T et al |
| 15485652 | 2004 | Organization of functional domains in the docking protein p130Cas. | Nasertorabi F et al |
| 21957230 | 2011 | Silencing of p130cas in ovarian carcinoma: a novel mechanism for tumor cell death. | Nick AM et al |
| 16919436 | 2006 | Interdependence of cell attachment and cell cycle signaling. | Pugacheva EN et al |
| 8070403 | 1994 | A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner. | Sakai R et al |
| 21291860 | 2011 | Integrin αβ1, αvβ, α6β effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance. | Sansing HA et al |
| 17129785 | 2006 | Force sensing by mechanical extension of the Src family kinase substrate p130Cas. | Sawada Y et al |
| 16914515 | 2006 | Invasion of host cells by Salmonella typhimurium requires focal adhesion kinase and p130Cas. | Shi J et al |
| 21630091 | 2011 | Urinary-type plasminogen activator receptor (uPAR) modulates oral cancer cell behavior with alteration in p130cas. | Shi Z et al |
| 18974122 | 2008 | A novel association between p130Cas and resistance to the chemotherapeutic drug adriamycin in human breast cancer cells. | Ta HQ et al |
| 21765937 | 2011 | NEDD9 and BCAR1 negatively regulate E-cadherin membrane localization, and promote E-cadherin degradation. | Tikhmyanova N et al |
| 17982677 | 2007 | Activation of the FAK-src molecular scaffolds and p130Cas-JNK signaling cascades by alpha1-integrins during colon cancer cell invasion. | Van Slambrouck S et al |
| 7673345 | 1995 | Focal adhesion formation by F9 embryonal carcinoma cells after vinculin gene disruption. | Volberg T et al |
| 8649368 | 1996 | Introduction of p130cas signaling complex formation upon integrin-mediated cell adhesion: a role for Src family kinases. | Vuori K et al |
| 7545676 | 1995 | Tyrosine phosphorylation of p130Cas and cortactin accompanies integrin-mediated cell adhesion to extracellular matrix. | Vuori K et al |
| 11207607 | 2000 | CAS/Crk signalling mediates uptake of Yersinia into human epithelial cells. | Weidow CL et al |
| 10741720 | 2000 | Colon cancer chemopreventive drugs modulate integrin-mediated signaling pathways. | Weyant MJ et al |
| 19667130 | 2009 | Multiparametric analysis of focal adhesion formation by RNAi-mediated gene knockdown. | Winograd-Katz SE et al |
| 11782456 | 2002 | Members of the Zyxin family of LIM proteins interact with members of the p130Cas family of signal transducers. | Yi J et al |
| 16095866 | 2005 | Neonatal cerebral hypoxia-ischemia: involvement of FAK-dependent pathway. | Zalewska T et al |
| 14567719 | 2003 | Growth factors and receptors in juvenile nasopharyngeal angiofibroma and nasal polyps: an immunohistochemical study. | Zhang PJ et al |
| 22034875 | 2011 | The docking protein p130Cas regulates cell sensitivity to proteasome inhibition. | Zhao M et al |
| 17524523 | 2007 | Transient forebrain ischemia effects FAK-coupled signaling in gerbil hippocampus. | Ziemka-Nałecz M et al |
| 10639513 | 2000 | Bcar1/p130Cas protein and primary breast cancer: prognosis and response to tamoxifen treatment. | van der Flier S et al |
Other Information
Locus ID:
NCBI: 9564
MIM: 602941
HGNC: 971
Ensembl: ENSG00000050820
Variants:
dbSNP: 9564
ClinVar: 9564
TCGA: ENSG00000050820
COSMIC: BCAR1
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA448871 | celecoxib | Chemical | Pathway | associated | 22336956 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36375119 | 2023 | BTG1 inactivation drives lymphomagenesis and promotes lymphoma dissemination through activation of BCAR1. | 3 |
| 36400248 | 2023 | The interaction of CFLAR with p130Cas promotes cell migration. | 3 |
| 36375119 | 2023 | BTG1 inactivation drives lymphomagenesis and promotes lymphoma dissemination through activation of BCAR1. | 3 |
| 36400248 | 2023 | The interaction of CFLAR with p130Cas promotes cell migration. | 3 |
| 34922945 | 2022 | Docking Protein p130Cas Regulates Acinar to Ductal Metaplasia During Pancreatic Adenocarcinoma Development and Pancreatitis. | 3 |
| 35031902 | 2022 | Comprehensive immunohistochemical analysis of RET, BCAR1, and BCAR3 expression in patients with Luminal A and B breast cancer subtypes. | 1 |
| 34922945 | 2022 | Docking Protein p130Cas Regulates Acinar to Ductal Metaplasia During Pancreatic Adenocarcinoma Development and Pancreatitis. | 3 |
| 35031902 | 2022 | Comprehensive immunohistochemical analysis of RET, BCAR1, and BCAR3 expression in patients with Luminal A and B breast cancer subtypes. | 1 |
| 33144694 | 2021 | Mutant TP53 interacts with BCAR1 to contribute to cancer cell invasion. | 5 |
| 34169835 | 2021 | A Cas-BCAR3 co-regulatory circuit controls lamellipodia dynamics. | 4 |
| 34192548 | 2021 | Targeting p130Cas- and microtubule-dependent MYC regulation sensitizes pancreatic cancer to ERK MAPK inhibition. | 10 |
| 34326687 | 2021 | BCAR1 plays critical roles in the formation and immunoevasion of invasive circulating tumor cells in lung adenocarcinoma. | 6 |
| 34830244 | 2021 | p130Cas Is Correlated with EREG Expression and a Prognostic Factor Depending on Colorectal Cancer Stage and Localization Reducing FOLFIRI Efficacy. | 0 |
| 33144694 | 2021 | Mutant TP53 interacts with BCAR1 to contribute to cancer cell invasion. | 5 |
| 34169835 | 2021 | A Cas-BCAR3 co-regulatory circuit controls lamellipodia dynamics. | 4 |
Citation
Allison Berrier
BCAR1 (breast cancer anti-estrogen resistance 1)
Atlas Genet Cytogenet Oncol Haematol. 2011-12-01
Online version: http://atlasgeneticsoncology.org/gene/761/bcar1
