BCAR3_BOVIN
ID BCAR3_BOVIN Reviewed; 826 AA.
AC Q58DL5; Q2KJF5;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 2.
DT 25-MAY-2022, entry version 92.
DE RecName: Full=Breast cancer anti-estrogen resistance protein 3 homolog;
GN Name=BCAR3;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). Promotes insulin-mediated
CC membrane ruffling (By similarity). In response to vasoconstrictor
CC peptide EDN1, involved in the activation of RAP1 downstream of PTK2B
CC via interaction with phosphorylated BCAR1. Inhibits cell migration and
CC invasion via regulation of TGFB-mediated matrix digestion, actin
CC filament rearrangement, and inhibition of invadopodia activity. May
CC inhibit TGFB-SMAD signaling, via facilitating BCAR1 and SMAD2 and/or
CC SMAD3 interaction (By similarity). Regulates EGF-induced DNA synthesis
CC (By similarity). Required for the maintenance of ocular lens morphology
CC and structural integrity, potentially via regulation of focal adhesion
CC complex signaling. Acts upstream of PTPRA to regulate the localization
CC of BCAR1 and PTPRA to focal adhesions, via regulation of SRC-mediated
CC phosphorylation of PTPRA. Positively regulates integrin-induced
CC tyrosine phosphorylation of BCAR1. 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 (By similarity). {ECO:0000250|UniProtKB:D3ZAZ5,
CC ECO:0000250|UniProtKB:O75815, ECO:0000250|UniProtKB:Q9QZK2}.
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 (By similarity). Within the
CC complex, interacts (via SH2 domain) with PTPRA (when phosphorylated on
CC 'Tyr-797') (By similarity). Interacts (via Ras-GEF domain) with BCAR1
CC (By similarity). Interacts with (via Ras-GEF domain) 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}.
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; BT021582; AAX46429.1; -; mRNA.
DR EMBL; BC105366; AAI05367.1; -; mRNA.
DR RefSeq; NP_001019654.1; NM_001024483.1.
DR RefSeq; XP_005204326.1; XM_005204269.3.
DR RefSeq; XP_005204327.1; XM_005204270.3.
DR RefSeq; XP_010801601.1; XM_010803299.2.
DR AlphaFoldDB; Q58DL5; -.
DR SMR; Q58DL5; -.
DR STRING; 9913.ENSBTAP00000055991; -.
DR iPTMnet; Q58DL5; -.
DR PaxDb; Q58DL5; -.
DR PRIDE; Q58DL5; -.
DR GeneID; 506231; -.
DR KEGG; bta:506231; -.
DR CTD; 8412; -.
DR eggNOG; ENOG502QPX3; Eukaryota.
DR HOGENOM; CLU_015281_0_0_1; -.
DR InParanoid; Q58DL5; -.
DR OrthoDB; 138275at2759; -.
DR TreeFam; TF323756; -.
DR Proteomes; UP000009136; Unplaced.
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:0001784; F:phosphotyrosine residue binding; ISS:UniProtKB.
DR GO; GO:0086100; P:endothelin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IBA:GO_Central.
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 2: Evidence at transcript 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 /evidence="ECO:0000250|UniProtKB:O75815"
FT CHAIN 2..826
FT /note="Breast cancer anti-estrogen resistance protein 3
FT homolog"
FT /id="PRO_0000230283"
FT DOMAIN 154..253
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 549..819
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT REGION 46..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 268..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 294..321
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 348..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 480..501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 745..749
FT /note="Mediates the interaction with BCAR1/p130CAS"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT COMPBIAS 268..283
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 348..371
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 291
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 335
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 359
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 364
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75815"
FT MOD_RES 472
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZK2"
FT CONFLICT 110
FT /note="L -> I (in Ref. 1; AAX46429)"
FT /evidence="ECO:0000305"
FT CONFLICT 764
FT /note="R -> K (in Ref. 2; AAI05367)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 826 AA; 92765 MW; 9E5EF3BFF75E9EB4 CRC64;
MAAGKFASLP RNMPVNHQFP LASSMDLLSS KSPLVERRAD AYQDVSIHGT LPRKKKGPPP
IRSCDNFSHV GTLPHSRSPR HHSPLIQDVI QEQPLQDWKG EAFTFRDQHL LDPTLEYVKF
SKERHVMDRT PERLKKELEE ELLLSSEDLR SHAWYHGRIP RQVSENLMQR DGDFLVRDSL
SSPGDFVLTC QWKNLPQHFK IRRTVVRLSE AYSRVQYQFE MESFDSIPGL VRCYVGNRRP
ISQQSGAIIF QPVNRTVPLR CLEERYGASS PDRAHEGSLT EGRPDAAKRL SLTVGGTQAR
EQGLPRGNLL RNKEKSGSQP ACLDHMQDRR ALSLKAHQSE SYLPIGGKLT PQSPSVGTSP
CPNSPVFRTG SEPTLSPAVV RRVSSDARPG EALRGSDSQL CPKPPPKPCK APLLKAPPSP
SIWLNSEANY CELNPALAAS YDGASRLPFC AQDSYVELLT AKQNGGLGTR NSDTSYLILD
DDDRTRPWKP PPAPGDTVGE DQDTFVMPLL ETTSSFKPND FESKLLPPEN KPLETSMLKR
AKELFTNSDP KVIAQHLLSV DCKVARILEV SEEMRKNMGV NSGLELITLP YGHQLRLDII
ERHNTMAIGI AVDILGCTGS LEDRAATLNK IIQVAVELKD SMGDLYSFSA IMKALEMPQI
TRLEKTWTAL RHQYTQTAIL YEKQLKPFSK VLHEGRESTC VPPNNVSVPL LMPLVTLMER
EAVTFEGTDM WEKNDESCEI MLNHLATARL MAEAADSYRM NAERILAGFQ PDEEMSEVFK
TEFQMRLLWG SKGAQVNQTE RYEKFNQILT ALSRKLEPPP VKQMEF
