BCAR3_HUMAN
ID BCAR3_HUMAN Reviewed; 825 AA.
AC O75815; D3DT43; Q5TEW3; Q6UW40; Q9BR50;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Breast cancer anti-estrogen resistance protein 3;
DE AltName: Full=Novel SH2-containing protein 2;
DE AltName: Full=SH2 domain-containing protein 3B;
GN Name=BCAR3; Synonyms=NSP2, SH2D3B; ORFNames=UNQ271/PRO308;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=9582273; DOI=10.1093/emboj/17.10.2799;
RA van Agthoven T., van Agthoven T.L.A., Dekker A., van der Spek P.J.,
RA Vreede L., Dorssers L.C.J.;
RT "Identification of BCAR3 by a random search for genes involved in
RT antiestrogen resistance of human breast cancer cells.";
RL EMBO J. 17:2799-2808(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=10187783; DOI=10.1074/jbc.274.15.10047;
RA Lu Y., Brush J., Stewart T.A.;
RT "NSP1 defines a novel family of adaptor proteins linking integrin and
RT tyrosine kinase receptors to the c-Jun N-terminal kinase/stress-activated
RT protein kinase signaling pathway.";
RL J. Biol. Chem. 274:10047-10052(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Heart;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182 AND SER-375, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP FUNCTION, AND INTERACTION WITH BCAR1 AND EGFR.
RX PubMed=18722344; DOI=10.1016/j.bbrc.2008.08.040;
RA Oh M.J., van Agthoven T., Choi J.E., Jeong Y.J., Chung Y.H., Kim C.M.,
RA Jhun B.H.;
RT "BCAR3 regulates EGF-induced DNA synthesis in normal human breast MCF-12A
RT cells.";
RL Biochem. Biophys. Res. Commun. 375:430-434(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32; SER-83; SER-290; SER-358;
RP SER-363 AND SER-375, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP FUNCTION, AND INTERACTION WITH BCAR1.
RX PubMed=19086031; DOI=10.1002/jcp.21649;
RA Rufanova V.A., Alexanian A., Wakatsuki T., Lerner A., Sorokin A.;
RT "Pyk2 mediates endothelin-1 signaling via p130Cas/BCAR3 cascade and
RT regulates human glomerular mesangial cell adhesion and spreading.";
RL J. Cell. Physiol. 219:45-56(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP IDENTIFICATION IN A COMPLEX WITH PTPRA; BCAR1 AND SRC, AND MUTAGENESIS OF
RP ARG-177 AND ARG-748.
RX PubMed=22801373; DOI=10.1128/mcb.00214-12;
RA Sun G., Cheng S.Y., Chen M., Lim C.J., Pallen C.J.;
RT "Protein tyrosine phosphatase alpha phosphotyrosyl-789 binds BCAR3 to
RT position Cas for activation at integrin-mediated focal adhesions.";
RL Mol. Cell. Biol. 32:3776-3789(2012).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP FUNCTION.
RX PubMed=24216110; DOI=10.1016/j.bbrc.2013.10.161;
RA Oh M.J., Yi S.J., Kim H.S., Kim J.H., Jeong Y.H., van Agthoven T.,
RA Jhun B.H.;
RT "Functional roles of BCAR3 in the signaling pathways of insulin leading to
RT DNA synthesis, membrane ruffling and GLUT4 translocation.";
RL Biochem. Biophys. Res. Commun. 441:911-916(2013).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78 AND SER-375, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-334 AND ARG-442, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [20] {ECO:0007744|PDB:3T6A}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 502-825, FUNCTION, INTERACTION
RP WITH BCAR1, AND MUTAGENESIS OF LEU-744 AND ARG-748.
RX PubMed=22081014; DOI=10.1038/nsmb.2152;
RA Mace P.D., Wallez Y., Dobaczewska M.K., Lee J.J., Robinson H.,
RA Pasquale E.B., Riedl S.J.;
RT "NSP-Cas protein structures reveal a promiscuous interaction module in cell
RT signaling.";
RL Nat. Struct. Mol. Biol. 18:1381-1387(2011).
CC -!- FUNCTION: Acts as an adapter protein downstream of several growth
CC factor receptors to promote cell proliferation, migration, and
CC redistribution of actin fibers (PubMed:24216110). Specifically involved
CC in INS/insulin signaling pathway by mediating MAPK1/ERK2-MAPK3/ERK1
CC activation and DNA synthesis (PubMed:24216110). Promotes insulin-
CC mediated membrane ruffling (By similarity). In response to
CC vasoconstrictor peptide EDN1, involved in the activation of RAP1
CC downstream of PTK2B via interaction with phosphorylated BCAR1
CC (PubMed:19086031). Inhibits cell migration and invasion via regulation
CC of TGFB-mediated matrix digestion, actin filament rearrangement, and
CC inhibition of invadopodia activity (By similarity). May inhibit TGFB-
CC SMAD signaling, via facilitating BCAR1 and SMAD2 and/or SMAD3
CC interaction (By similarity). Regulates EGF-induced DNA synthesis
CC (PubMed:18722344). Required for the maintenance of ocular lens
CC morphology and structural integrity, potentially via regulation of
CC focal adhesion complex signaling (By similarity). Acts upstream of
CC PTPRA to regulate the localization of BCAR1 and PTPRA to focal
CC adhesions, via regulation of SRC-mediated phosphorylation of PTPRA (By
CC similarity). Positively regulates integrin-induced tyrosine
CC phosphorylation of BCAR1 (By similarity). Acts as a guanine nucleotide
CC exchange factor (GEF) for small GTPases RALA, RAP1A and RRAS (By
CC similarity). However, in a contrasting study, lacks GEF activity
CC towards RAP1 (PubMed:22081014). {ECO:0000250|UniProtKB:D3ZAZ5,
CC ECO:0000250|UniProtKB:Q9QZK2, ECO:0000269|PubMed:18722344,
CC ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:22081014,
CC ECO:0000269|PubMed:24216110}.
CC -!- SUBUNIT: Part of a complex comprised of PTPRA, BCAR1, BCAR3 (via SH2
CC domain) and SRC; the formation of the complex is dependent on integrin
CC mediated-tyrosine phosphorylation of PTPRA (PubMed:22801373). Within
CC the complex, interacts (via SH2 domain) with PTPRA (when phosphorylated
CC on 'Tyr-798') (PubMed:22801373). Interacts (via Ras-GEF domain) with
CC BCAR1 (PubMed:18722344, PubMed:19086031, PubMed:22081014). Interacts
CC (via Ras-GEF domain) with NEDD9 (By similarity). Interacts with
CC PTK2/FAK1 (By similarity). Interacts with PTPN1. Interacts (via SH2
CC domain) with EGFR (when tyrosine-phosphorylated) (PubMed:18722344).
CC {ECO:0000250|UniProtKB:Q9QZK2, ECO:0000269|PubMed:18722344,
CC ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:22081014,
CC ECO:0000269|PubMed:22801373}.
CC -!- INTERACTION:
CC O75815; Q9BXS5: AP1M1; NbExp=3; IntAct=EBI-702336, EBI-541426;
CC O75815; Q2TAC2-2: CCDC57; NbExp=3; IntAct=EBI-702336, EBI-10961624;
CC O75815; P04626: ERBB2; NbExp=2; IntAct=EBI-702336, EBI-641062;
CC O75815; P35637: FUS; NbExp=3; IntAct=EBI-702336, EBI-400434;
CC O75815; O95995: GAS8; NbExp=3; IntAct=EBI-702336, EBI-1052570;
CC O75815; P35568: IRS1; NbExp=3; IntAct=EBI-702336, EBI-517592;
CC O75815; P10721: KIT; NbExp=3; IntAct=EBI-702336, EBI-1379503;
CC O75815; Q14511: NEDD9; NbExp=4; IntAct=EBI-702336, EBI-2108053;
CC O75815; Q9UJX0: OSGIN1; NbExp=4; IntAct=EBI-702336, EBI-9057006;
CC O75815; P57075-2: UBASH3A; NbExp=3; IntAct=EBI-702336, EBI-7353612;
CC O75815-1; P56945: BCAR1; NbExp=3; IntAct=EBI-15953103, EBI-702093;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9QZK2}. Cell
CC junction, focal adhesion {ECO:0000250|UniProtKB:Q9QZK2}.
CC Note=Localization to focal adhesions depends on interaction with PTPRA.
CC {ECO:0000250|UniProtKB:Q9QZK2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O75815-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75815-2; Sequence=VSP_017814;
CC Name=3;
CC IsoId=O75815-3; Sequence=VSP_046716, VSP_046717;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Found in several cancer
CC cell lines, but not in nonmalignant breast tissue.
CC {ECO:0000269|PubMed:10187783, ECO:0000269|PubMed:9582273}.
CC -!- DOMAIN: The SH2 domain mediates interaction with tyrosine-
CC phosphorylated proteins (PubMed:18722344). However, not involved in the
CC binding to phosphorylated BCAR1 (PubMed:18722344). Required for cell
CC cycle progression in response to INS/insulin (PubMed:24216110).
CC Required for regulation of EFR-induced DNA synthesis (PubMed:18722344).
CC {ECO:0000269|PubMed:18722344, ECO:0000269|PubMed:24216110}.
CC -!- DOMAIN: The Ras-GEF domain appears to adopt a closed conformation
CC rendering it incapable of carrying out canonical exchange factor
CC function, this closed conformation is probably required for interaction
CC with BCAR1. {ECO:0000269|PubMed:22081014}.
CC -!- PTM: Phosphorylated on tyrosine residues.
CC {ECO:0000250|UniProtKB:Q9QZK2}.
CC -!- MISCELLANEOUS: Overexpression confers anti-estrogen resistance via
CC RRAS-independent activation of the PI3K pathway, and activation of the
CC cyclin D1 promoter in breast cancer cell lines (PubMed:9582273). Plays
CC a role in insulin-mediated ERK activation and DNA synthesis in breast
CC cancer cells (PubMed:24216110). {ECO:0000269|PubMed:24216110,
CC ECO:0000269|PubMed:9582273}.
CC -!- CAUTION: The guanine nucleotide exchange factor (GEF) activity is
CC controversial. One study showed GEF activity towards RALA, RAP1A and
CC RRAS (By similarity). However, in another study, a construct containing
CC only the Ras-GEF domain lacks GEF activity towards RAP1
CC (PubMed:22081014). {ECO:0000250|UniProtKB:Q9QZK2,
CC ECO:0000269|PubMed:22081014}.
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DR EMBL; U92715; AAC39777.1; -; mRNA.
DR EMBL; AF124250; AAD28245.1; -; mRNA.
DR EMBL; AY358996; AAQ89355.1; -; mRNA.
DR EMBL; AL833121; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL049796; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL109613; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359820; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL512488; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471097; EAW73065.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW73066.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW73068.1; -; Genomic_DNA.
DR EMBL; BC039895; AAH39895.1; -; mRNA.
DR CCDS; CCDS58010.1; -. [O75815-3]
DR CCDS; CCDS745.1; -. [O75815-1]
DR CCDS; CCDS76181.1; -. [O75815-2]
DR RefSeq; NP_001248337.1; NM_001261408.1. [O75815-1]
DR RefSeq; NP_001248338.1; NM_001261409.1. [O75815-1]
DR RefSeq; NP_001248339.1; NM_001261410.1. [O75815-3]
DR RefSeq; NP_001295180.1; NM_001308251.1. [O75815-2]
DR RefSeq; NP_003558.1; NM_003567.3. [O75815-1]
DR RefSeq; XP_016857969.1; XM_017002480.1. [O75815-1]
DR PDB; 3T6A; X-ray; 2.40 A; A/B/C/D=502-825.
DR PDBsum; 3T6A; -.
DR AlphaFoldDB; O75815; -.
DR SMR; O75815; -.
DR BioGRID; 114000; 64.
DR DIP; DIP-33857N; -.
DR IntAct; O75815; 42.
DR MINT; O75815; -.
DR STRING; 9606.ENSP00000359264; -.
DR iPTMnet; O75815; -.
DR PhosphoSitePlus; O75815; -.
DR BioMuta; BCAR3; -.
DR EPD; O75815; -.
DR jPOST; O75815; -.
DR MassIVE; O75815; -.
DR MaxQB; O75815; -.
DR PaxDb; O75815; -.
DR PeptideAtlas; O75815; -.
DR PRIDE; O75815; -.
DR ProteomicsDB; 50205; -. [O75815-1]
DR ProteomicsDB; 50206; -. [O75815-2]
DR ProteomicsDB; 65066; -.
DR Antibodypedia; 2973; 170 antibodies from 34 providers.
DR DNASU; 8412; -.
DR Ensembl; ENST00000260502.11; ENSP00000260502.6; ENSG00000137936.18. [O75815-1]
DR Ensembl; ENST00000370243.1; ENSP00000359263.1; ENSG00000137936.18. [O75815-1]
DR Ensembl; ENST00000370244.5; ENSP00000359264.1; ENSG00000137936.18. [O75815-1]
DR Ensembl; ENST00000370247.7; ENSP00000359267.3; ENSG00000137936.18. [O75815-3]
DR Ensembl; ENST00000539242.5; ENSP00000441343.1; ENSG00000137936.18. [O75815-2]
DR GeneID; 8412; -.
DR KEGG; hsa:8412; -.
DR MANE-Select; ENST00000260502.11; ENSP00000260502.6; NM_003567.4; NP_003558.1.
DR UCSC; uc001dpx.6; human. [O75815-1]
DR CTD; 8412; -.
DR DisGeNET; 8412; -.
DR GeneCards; BCAR3; -.
DR HGNC; HGNC:973; BCAR3.
DR HPA; ENSG00000137936; Low tissue specificity.
DR MIM; 604704; gene.
DR neXtProt; NX_O75815; -.
DR OpenTargets; ENSG00000137936; -.
DR PharmGKB; PA25283; -.
DR VEuPathDB; HostDB:ENSG00000137936; -.
DR eggNOG; ENOG502QPX3; Eukaryota.
DR GeneTree; ENSGT00940000154130; -.
DR HOGENOM; CLU_015281_0_0_1; -.
DR InParanoid; O75815; -.
DR OMA; RSDAYQD; -.
DR OrthoDB; 138275at2759; -.
DR PhylomeDB; O75815; -.
DR TreeFam; TF323756; -.
DR PathwayCommons; O75815; -.
DR SignaLink; O75815; -.
DR BioGRID-ORCS; 8412; 30 hits in 1072 CRISPR screens.
DR ChiTaRS; BCAR3; human.
DR GeneWiki; BCAR3; -.
DR GenomeRNAi; 8412; -.
DR Pharos; O75815; Tbio.
DR PRO; PR:O75815; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O75815; protein.
DR Bgee; ENSG00000137936; Expressed in parotid gland and 190 other tissues.
DR ExpressionAtlas; O75815; baseline and differential.
DR Genevisible; O75815; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:UniProtKB-KW.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IMP:UniProtKB.
DR GO; GO:0086100; P:endothelin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0002089; P:lens morphogenesis in camera-type eye; IEA:Ensembl.
DR GO; GO:0045740; P:positive regulation of DNA replication; IMP:UniProtKB.
DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0009410; P:response to xenobiotic stimulus; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR CDD; cd00155; RasGEF; 1.
DR CDD; cd10337; SH2_BCAR3; 1.
DR Gene3D; 1.10.840.10; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR028849; BCAR3.
DR InterPro; IPR023578; Ras_GEF_dom_sf.
DR InterPro; IPR001895; RASGEF_cat_dom.
DR InterPro; IPR036964; RASGEF_cat_dom_sf.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR044102; SH2_SHEP1/BCAR3/NSP1.
DR PANTHER; PTHR14247:SF10; PTHR14247:SF10; 1.
DR Pfam; PF00617; RasGEF; 1.
DR Pfam; PF00017; SH2; 1.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF48366; SSF48366; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50009; RASGEF_CAT; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell junction; Cytoplasm;
KW Guanine-nucleotide releasing factor; Methylation; Phosphoprotein;
KW Reference proteome; SH2 domain.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..825
FT /note="Breast cancer anti-estrogen resistance protein 3"
FT /id="PRO_0000230284"
FT DOMAIN 154..253
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 548..818
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT REGION 40..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 744..748
FT /note="Mediates the interaction with BCAR1/p130CAS"
FT /evidence="ECO:0000305|PubMed:22081014"
FT COMPBIAS 74..93
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 78
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 182
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243"
FT MOD_RES 290
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 334
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 442
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZK2"
FT VAR_SEQ 1..324
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_017814"
FT VAR_SEQ 1..91
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_046716"
FT VAR_SEQ 92..117
FT /note="ESPWQDRHGETFTFRDPHLLDPTVEY -> MPKECSAFHALSAALCCFYHRK
FT SFIG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_046717"
FT VARIANT 464
FT /note="E -> G (in dbSNP:rs12062278)"
FT /id="VAR_050689"
FT VARIANT 593
FT /note="Q -> H (in dbSNP:rs17110107)"
FT /id="VAR_050690"
FT MUTAGEN 177
FT /note="R->K: Abolishes localization to focal adhesions.
FT Reduces interaction with PTPRA."
FT /evidence="ECO:0000269|PubMed:22801373"
FT MUTAGEN 744
FT /note="L->E: Weakens interaction with BCAR1."
FT /evidence="ECO:0000269|PubMed:22081014"
FT MUTAGEN 748
FT /note="R->A: Abolishes interaction with BCAR1 and SRC."
FT /evidence="ECO:0000269|PubMed:22081014,
FT ECO:0000269|PubMed:22801373"
FT CONFLICT 519
FT /note="E -> G (in Ref. 4; AL833121)"
FT /evidence="ECO:0000305"
FT CONFLICT 543
FT /note="L -> P (in Ref. 4; AL833121)"
FT /evidence="ECO:0000305"
FT HELIX 517..519
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 534..546
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 549..563
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 571..577
FT /evidence="ECO:0007829|PDB:3T6A"
FT STRAND 578..580
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 582..585
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 589..591
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 592..614
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 620..639
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 644..655
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 657..660
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 663..672
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 674..682
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 684..692
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 696..698
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 711..717
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 724..726
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 732..734
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 737..752
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 754..764
FT /evidence="ECO:0007829|PDB:3T6A"
FT TURN 765..767
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 772..777
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 780..792
FT /evidence="ECO:0007829|PDB:3T6A"
FT HELIX 797..815
FT /evidence="ECO:0007829|PDB:3T6A"
SQ SEQUENCE 825 AA; 92566 MW; C55D61BB4AC7D0F2 CRC64;
MAAGKFASLP RNMPVNHQFP LASSMDLLSS RSPLAEHRPD AYQDVSIHGT LPRKKKGPPP
IRSCDDFSHM GTLPHSKSPR QNSPVTQDGI QESPWQDRHG ETFTFRDPHL LDPTVEYVKF
SKERHIMDRT PEKLKKELEE ELLLSSEDLR SHAWYHGRIP RQVSENLVQR DGDFLVRDSL
SSPGNFVLTC QWKNLAQHFK INRTVLRLSE AYSRVQYQFE MESFDSIPGL VRCYVGNRRP
ISQQSGAIIF QPINRTVPLR CLEEHYGTSP GQAREGSLTK GRPDVAKRLS LTMGGVQARE
QNLPRGNLLR NKEKSGSQPA CLDHMQDRRA LSLKAHQSES YLPIGCKLPP QSSGVDTSPC
PNSPVFRTGS EPALSPAVVR RVSSDARAGE ALRGSDSQLC PKPPPKPCKV PFLKVPSSPS
AWLNSEANYC ELNPAFATGC GRGAKLPSCA QGSHTELLTA KQNEAPGPRN SGVNYLILDD
DDRERPWEPA AAQMEKGQWD KGEFVTPLLE TVSSFRPNEF ESKFLPPENK PLETAMLKRA
KELFTNNDPK VIAQHVLSMD CRVARILGVS EEMRRNMGVS SGLELITLPH GHQLRLDIIE
RHNTMAIGIA VDILGCTGTL EDRAATLSKI IQVAVELKDS MGDLYSFSAL MKALEMPQIT
RLEKTWTALR HQYTQTAILY EKQLKPFSKL LHEGRESTCV PPNNVSVPLL MPLVTLMERQ
AVTFEGTDMW EKNDQSCEIM LNHLATARFM AEAADSYRMN AERILAGFQP DEEMNEICKT
EFQMRLLWGS KGAQVNQTER YEKFNQILTA LSRKLEPPPV KQAEL
