BCAR3_RAT
ID BCAR3_RAT Reviewed; 825 AA.
AC D3ZAZ5;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Breast cancer anti-estrogen resistance protein 3 homolog {ECO:0000305};
DE AltName: Full=BCAR3 adapter protein, NSP family member {ECO:0000305};
DE AltName: Full=Novel SH2-containing protein 2 {ECO:0000305};
DE AltName: Full=SH2 domain-containing protein 3B {ECO:0000305};
DE AltName: Full=p130Cas-binding protein AND-34 {ECO:0000305};
GN Name=Bcar3 {ECO:0000312|RGD:1311688};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000312|Proteomes:UP000002494};
RN [1] {ECO:0000312|Proteomes:UP000002494}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000312|Proteomes:UP000002494};
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2] {ECO:0000312|EMBL:EDL82101.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0007744|PubMed:22673903}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [4] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH BCAR1.
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).
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 (By similarity). 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 (PubMed:24216110). In response to
CC vasoconstrictor peptide EDN1, involved in the activation of RAP1
CC downstream of PTK2B via interaction with phosphorylated BCAR1 (By
CC similarity). Inhibits cell migration and invasion via regulation of
CC TGFB-mediated matrix digestion, actin filament rearrangement, and
CC inhibition of invadopodia activity (By similarity). May inhibit
CC TGFB/SMAD signaling, via facilitating BCAR1 and SMAD2 and/or SMAD3
CC interaction (By similarity). Regulates EGF-induced DNA synthesis (By
CC similarity). Required for the maintenance of ocular lens morphology and
CC structural integrity, potentially via regulation of focal adhesion
CC complex signaling (By similarity). Acts upstream of PTPRA to regulate
CC the localization of BCAR1 and PTPRA to focal adhesions, via regulation
CC of SRC-mediated phosphorylation of PTPRA (By similarity). Positively
CC regulates integrin-induced tyrosine phosphorylation of BCAR1 (By
CC similarity). Acts as a guanine nucleotide exchange factor (GEF) for
CC small GTPases RALA, RAP1A and RRAS (By similarity). However, in a
CC contrasting study, lacks GEF activity towards RAP1 (By similarity).
CC {ECO:0000250|UniProtKB:O75815, ECO:0000250|UniProtKB:Q9QZK2,
CC ECO:0000269|PubMed:24216110}.
CC -!- SUBUNIT: Part of a complex comprised of PTPRA, BCAR1, BCAR3 and SRC;
CC the formation of the complex is dependent on integrin mediated-tyrosine
CC phosphorylation of PTPRA (By similarity). Within the complex, interacts
CC (via SH2 domain) with PTPRA (when phosphorylated on 'Tyr-792') (By
CC similarity). Interacts (via Ras-GEF domain) with BCAR1
CC (PubMed:24216110). Interacts (via Ras-GEF domain) with NEDD9 (By
CC similarity). Interacts with PTK2/FAK1 (By similarity). Interacts with
CC PTPN1. Interacts (via SH2 domain) with EGFR (when tyrosine-
CC phosphorylated) (By similarity). {ECO:0000250|UniProtKB:O75815,
CC ECO:0000250|UniProtKB:Q9QZK2, ECO:0000269|PubMed:24216110}.
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 -!- DOMAIN: The SH2 domain mediates interaction with tyrosine-
CC phosphorylated proteins (By similarity). However, not involved in the
CC binding to phosphorylated BCAR1 (By similarity). Required for cell
CC cycle progression in response to INS/insulin (By similarity). Required
CC for regulation of EGF-induced DNA synthesis (By similarity).
CC {ECO:0000250|UniProtKB:O75815, ECO:0000250|UniProtKB:Q9QZK2}.
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:0000250|UniProtKB:O75815}.
CC -!- PTM: Phosphorylated on tyrosine residues.
CC {ECO:0000250|UniProtKB:Q9QZK2}.
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 (By
CC similarity). {ECO:0000250|UniProtKB:O75815,
CC ECO:0000250|UniProtKB:Q9QZK2}.
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DR EMBL; AABR07013194; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07013195; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07013196; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07013197; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07013198; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07013199; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07013200; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473952; EDL82101.1; -; Genomic_DNA.
DR RefSeq; NP_001101192.1; NM_001107722.1.
DR AlphaFoldDB; D3ZAZ5; -.
DR SMR; D3ZAZ5; -.
DR STRING; 10116.ENSRNOP00000062880; -.
DR iPTMnet; D3ZAZ5; -.
DR PhosphoSitePlus; D3ZAZ5; -.
DR PaxDb; D3ZAZ5; -.
DR PeptideAtlas; D3ZAZ5; -.
DR Ensembl; ENSRNOT00000065111; ENSRNOP00000062880; ENSRNOG00000013737.
DR GeneID; 310838; -.
DR KEGG; rno:310838; -.
DR CTD; 8412; -.
DR RGD; 1311688; Bcar3.
DR eggNOG; ENOG502QPX3; Eukaryota.
DR GeneTree; ENSGT00940000154130; -.
DR HOGENOM; CLU_015281_0_0_1; -.
DR InParanoid; D3ZAZ5; -.
DR OMA; RSDAYQD; -.
DR OrthoDB; 138275at2759; -.
DR TreeFam; TF323756; -.
DR PRO; PR:D3ZAZ5; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Proteomes; UP000234681; Chromosome 2.
DR Bgee; ENSRNOG00000013737; Expressed in jejunum and 20 other tissues.
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; ISO:RGD.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISS:UniProtKB.
DR GO; GO:0086100; P:endothelin receptor signaling pathway; ISO:RGD.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0002089; P:lens morphogenesis in camera-type eye; ISO:RGD.
DR GO; GO:0045740; P:positive regulation of DNA replication; ISS:UniProtKB.
DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
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 Acetylation; Cell junction; Cytoplasm; Guanine-nucleotide releasing factor;
KW Methylation; Phosphoprotein; Reference proteome; SH2 domain.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..825
FT /note="Breast cancer anti-estrogen resistance protein 3
FT homolog"
FT /id="PRO_0000449050"
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..84
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 300..320
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:0000250|UniProtKB:O75815"
FT COMPBIAS 69..84
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 78
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 182
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 290
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 334
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZK2"
FT MOD_RES 442
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZK2"
SQ SEQUENCE 825 AA; 92477 MW; 473EA12F02A892E1 CRC64;
MAAGKFASLP RHMPVNHQFP LASSMDLLSS KSPLAEHRTE AYPDVSIHGT LPRKKKGPPP
IRSCDSASHM GTLPHSKSPR QSSPLTQDLI LEKPLPDWKG DSFAFRDPYL LDPTLEYVKF
SKERHIMDRT PERLKKELEE ELLLSSEDLR SHAWYHGRIP RQVSENLVQR DGDFLVRDSL
SSPGNFVLTC QWKNLAQHFK INRTVLRLSE AYSRVQYQFE MESFDSIPGL VRCYVGNRRP
ISQQSGAIIF QPINRTVPLW CLEERYGTSP GRGREGSFAE GRPDVVKRLS LTTGGIQARD
HSLPRGNLLR NKDKSGSQPA CLDHVQDRKA ATLKAHQSES HLPIGCKLPP QSPSVDTSPC
PNSPVFRTGS EPTLSPALVR RFSSDARAGE ALRGSDSQLC PKPPPKPCKV PFLKVPPSPS
PWLNSEANYC ELNPAFAVGC DRGAKLLSQA LDSHEMLLTA KQNGASGPRN SGINYSILDG
DDQGRHWDPL AVQTDEGQED ETKFVPPVME TVSSFRPNDF ESKLLPPENK PLETAMLKHA
KELFTNHDAR VIAQHMLSVD CKVARILEVS EDMKRSMGVS SGLELITLPH GRQLRLDIIE
RHNTMAIGIA VDILGCTGTL ENRAGTLNKI IQVAMELKDT MGDLYSFSAI MKALEMPQIT
RLEKTWTALR HHYTQTAILY EKQLKPFSKI LHEGRESTYV PASSVSVPLL MPLVTLMERQ
AVTFEGTDMW EKNDESCEIM LSHLATARFM AEASESYRMN AERVLADFQP DEEMTEILKT
EFQMRLLWGS KGAEVNQNER YDKFNQILTA LSRKLEPPSG KQAEL
