BCAR3_MACFA
ID BCAR3_MACFA Reviewed; 825 AA.
AC Q4R8R1;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 2.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Breast cancer anti-estrogen resistance protein 3 homolog;
GN Name=BCAR3; ORFNames=QtsA-11767;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-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-798') (By similarity). Interacts (via Ras-GEF domain) with BCAR1
CC (By similarity). 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}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE00510.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB168388; BAE00510.1; ALT_INIT; mRNA.
DR RefSeq; NP_001272015.1; NM_001285086.1.
DR AlphaFoldDB; Q4R8R1; -.
DR SMR; Q4R8R1; -.
DR STRING; 9541.XP_005542749.1; -.
DR GeneID; 101867222; -.
DR CTD; 8412; -.
DR eggNOG; ENOG502QPX3; Eukaryota.
DR OrthoDB; 138275at2759; -.
DR Proteomes; UP000233100; 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: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..825
FT /note="Breast cancer anti-estrogen resistance protein 3
FT homolog"
FT /id="PRO_0000230285"
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 31..93
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 73..93
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:O75815"
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; 92592 MW; 7384B4A51AB6FE4D CRC64;
MAAGKFASLP RNMPVNHQFP LASSMDLLSS KSPLTEHRPD AYQDVSIHGT LPRKKKGPPP
IRSCDDFSHM GTLPHSKSPQ QNSPVTQDSI QESPWQDRHC ETFTFRDPHL LDPTLEYVKF
SKERHIMDRT PEKLKKELEE ELLLSSEDLR SHAWYHGRIP RQVSENLVQR DGDFLVRDSL
SSPGNFVLTC QWKNLAQHFK INRTVLRLSE AYSRVQYQFE MESFDSIPGL VRCYVGNRRP
ISQQSGAIIF QPINRTVPLR CLEERYGISP GQAREGSLTE GRPDVTKRLS LTMGGVQARE
QNLPRGNLLR NKEKSGSQPA CLDHMQDRRA LSLKAHQSES YLPIGCKLPP QSSGVDTSPC
PNSPVFRTGS EPALSPAVVR RVSSDARAGE ALRGSDSQLC PKPPPKPCKV PFLKAPSSPS
AWLNSEANYC ELNPAFATGC GRGAKLPLCA QGSPTELLTA KQNGALGPRN SGINYLILDD
DDRERPWEPA AAQTEKGQWD KGEFVAPLLE TVSSFRPNDF KSKFLPPENK PLETAMLKRA
KELFTNNDPK VIAQHILSMD CRVARILEVS EEMRRNMGVS SGLELITLPH GHQLRLDIIE
RHSTMAIGIA VYILGCTGTL EDRAATLSKV IQVAVELKDS MGDLYSFSAL MKALEMPQIT
RLEKTWTALR HQYTQTAILY EKQLKPFSKI LHEGRESTCV PPNNVSVPLL MPLVTLMERQ
AVTFEGTDMW EKNDQSCEIM LNHLATARLM AEATDSYRMN AERILAGFQP DEEMNEICKT
EFQMRLLWGS KGAQVNQAER YEKFNQILTA LSRKLEPPPV KQAEL
