BCAR3 Gene

HGNC Family	SH2 domain containing
Name	breast cancer anti-estrogen resistance 3
Description	Breast tumors are initially dependent on estrogens for growth and progression and can be inhibited by anti-estrogens such as tamoxifen. However, breast cancers progress to become anti-estrogen resistant. Breast cancer anti-estrogen resistance gene 3 was identified in the search for genes involved in the development of estrogen resistance. The gene encodes a component of intracellular signal transduction that causes estrogen-independent proliferation in human breast cancer cells. The protein contains a putative src homology 2 (SH2) domain, a hall mark of cellular tyrosine kinase signaling molecules, and is partly homologous to the cell division cycle protein CDC48. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BCAR3 (also known as AND‐34 or NSP2) functions as a multifaceted adaptor protein that integrates signals from growth factor receptors and integrin‐mediated adhesion complexes to modulate cell behavior. In breast cancer, elevated BCAR3 expression has been shown to promote cytoskeletal remodeling, membrane protrusiveness, and migration through its tight association with the focal adhesion protein p130Cas. This interaction facilitates the assembly of signaling complexes that activate Src family kinases, Rac and PI3K/Akt cascades, thereby contributing to anti‐estrogen resistance and estrogen‐independent proliferation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In experimental models, over‐expression of BCAR3 disrupts cadherin‐mediated cell–cell adhesion and augments motility, while disruption of the BCAR3–p130Cas complex impairs migration and can re‐sensitize resistant cells to anti‐estrogens."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " Structural studies further reveal that BCAR3 adopts a “closed” conformation that permits high‐affinity, promiscuous binding to Cas family proteins, thus acting as an enzyme–to–adaptor conversion module that bridges diverse signaling inputs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In addition, in other cell types such as B lymphocytes, mesangial cells, and lens epithelial cells, BCAR3 regulates small GTPases and focal adhesion turnover—processes essential for proper adhesion, cell spreading, and survival."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": " Moreover, emerging evidence suggests that BCAR3 can antagonize prometastatic transforming growth factor β (TGFβ)/Smad signaling, thereby potentially suppressing invasive progression in breast tumors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Collectively, BCAR3 stands out as a pivotal modulator of cell adhesion, migration, and endocrine resistance in breast cancer through its regulation of key downstream signaling pathways, making it a promising target for therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Randy S Schrecengost, Rebecca B Riggins, Keena S Thomas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Breast cancer antiestrogen resistance-3 expression regulates breast cancer cell migration through promotion of p130Cas membrane localization and membrane ruffling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-06-3455"}], "href": "https://doi.org/10.1158/0008-5472.CAN-06-3455"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17616674"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17616674"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kyriacos N Felekkis, Radha P Narsimhan, Richard Near, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AND-34 activates phosphatidylinositol 3-kinase and induces anti-estrogen resistance in a SH2 and GDP exchange factor-like domain-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2005)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15671247"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15671247"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Natasha R Schuh, Michael S Guerrero, Randy S Schrecengost, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BCAR3 regulates Src/p130 Cas association, Src kinase activity, and breast cancer adhesion signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.046631"}], "href": "https://doi.org/10.1074/jbc.M109.046631"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19940159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19940159"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Anthony Makkinje, Pierre Vanden Borre, Richard I Near, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Breast cancer anti-estrogen resistance 3 (BCAR3) protein augments binding of the c-Src SH3 domain to Crk-associated substrate (p130cas)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.389981"}], "href": "https://doi.org/10.1074/jbc.M112.389981"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22711540"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22711540"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yi Yu, Larry A Feig "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of R-Ras and Ral GTPases in estrogen-independent proliferation of breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1205961"}], "href": "https://doi.org/10.1038/sj.onc.1205961"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12386818"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12386818"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yann Wallez, Stefan J Riedl, Elena B Pasquale "}, {"type": "b", "children": [{"type": "t", "text": "Association of the breast cancer antiestrogen resistance protein 1 (BCAR1) and BCAR3 scaffolding proteins in cell signaling and antiestrogen resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.541839"}], "href": "https://doi.org/10.1074/jbc.M113.541839"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24584939"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24584939"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Shefali Soni, Bor-Tyh Lin, Avery August, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of a phosphorylated p130(Cas) substrate domain attenuates the phosphatidylinositol 3-kinase/Akt survival pathway in tamoxifen resistant breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.22136"}], "href": "https://doi.org/10.1002/jcb.22136"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19330798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19330798"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Marie-Line Garron, Diana Arsenieva, Jessie Zhong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural insights into the association between BCAR3 and Cas family members, an atypical complex implicated in anti-oestrogen resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2008.12.010"}], "href": "https://doi.org/10.1016/j.jmb.2008.12.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19103205"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19103205"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Dongpo Cai, Kyriakos N Felekkis, Richard I Near, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The GDP exchange factor AND-34 is expressed in B cells, associates with HEF1, and activates Cdc42."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.170.2.969"}], "href": "https://doi.org/10.4049/jimmunol.170.2.969"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12517963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12517963"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Richard I Near, Richard S Smith, Paul A Toselli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of AND-34/BCAR3 expression in mice results in rupture of the adult lens."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Vis (2009)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19365570"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19365570"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Elena Campos-Sanchez, Nerea Deleyto-Seldas, Veronica Dominguez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2017.04.069"}], "href": "https://doi.org/10.1016/j.celrep.2017.04.069"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28538178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28538178"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jimin Guo, Lucie Canaff, Charles Vincent Rajadurai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Breast cancer anti-estrogen resistance 3 inhibits transforming growth factor β/Smad signaling and associates with favorable breast cancer disease outcomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13058-014-0476-9"}], "href": "https://doi.org/10.1186/s13058-014-0476-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25499443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25499443"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Pierre Vanden Borre, Richard I Near, Anthony Makkinje, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BCAR3/AND-34 can signal independent of complex formation with CAS family members or the presence of p130Cas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2011.01.018"}], "href": "https://doi.org/10.1016/j.cellsig.2011.01.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21262352"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21262352"}]}]}]}
Synonyms	SH2D3B, AND-34
Proteins	BCAR3_HUMAN
NCBI Gene ID	8412
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

BCAR3 has 8,596 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 119 datasets.

Click the + buttons to view associations for BCAR3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

BCAR3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by BCAR3 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of BCAR3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of BCAR3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of BCAR3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of BCAR3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of BCAR3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of BCAR3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of BCAR3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of BCAR3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of BCAR3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of BCAR3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of BCAR3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of BCAR3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with BCAR3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with BCAR3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of BCAR3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of BCAR3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of BCAR3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of BCAR3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing BCAR3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing BCAR3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing BCAR3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with BCAR3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with BCAR3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of BCAR3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with BCAR3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with BCAR3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with BCAR3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of BCAR3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by BCAR3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with BCAR3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with BCAR3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with BCAR3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with BCAR3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with BCAR3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at BCAR3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of BCAR3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of BCAR3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing BCAR3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with BCAR3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.