BCAR1_RAT
ID BCAR1_RAT Reviewed; 968 AA.
AC Q63767; Q63766;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Breast cancer anti-estrogen resistance protein 1;
DE AltName: Full=CRK-associated substrate;
DE AltName: Full=p130cas;
GN Name=Bcar1; Synonyms=Cas, Crkas;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Fibroblast;
RX PubMed=8070403; DOI=10.1002/j.1460-2075.1994.tb06684.x;
RA Sakai R., Iwamatsu A., Hirano N., Ogawa S., Tanaka T., Mano H., Yazaki Y.,
RA Hirai H.;
RT "A novel signaling molecule, p130, forms stable complexes in vivo with v-
RT Crk and v-Src in a tyrosine phosphorylation-dependent manner.";
RL EMBO J. 13:3748-3756(1994).
RN [2]
RP PHOSPHORYLATION AT TYR-347 BY ABL1.
RX PubMed=7780740; DOI=10.1016/s0960-9822(95)00060-1;
RA Mayer B.J., Hirai H., Sakai R.;
RT "Evidence that SH2 domains promote processive phosphorylation by protein-
RT tyrosine kinases.";
RL Curr. Biol. 5:296-305(1995).
RN [3]
RP PHOSPHORYLATION AT TYROSINE RESIDUES BY PTK2/FAK1.
RX PubMed=9360983; DOI=10.1074/jbc.272.46.29083;
RA Tachibana K., Urano T., Fujita H., Ohashi Y., Kamiguchi K., Iwata S.,
RA Hirai H., Morimoto C.;
RT "Tyrosine phosphorylation of Crk-associated substrates by focal adhesion
RT kinase. A putative mechanism for the integrin-mediated tyrosine
RT phosphorylation of Crk-associated substrates.";
RL J. Biol. Chem. 272:29083-29090(1997).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-737, AND IDENTIFICATION BY
RP 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).
CC -!- FUNCTION: Docking protein which plays a central coordinating role for
CC tyrosine-kinase-based signaling related to cell adhesion (By
CC similarity). Implicated in induction of cell migration and cell
CC branching (By similarity). Involved in the BCAR3-mediated inhibition of
CC TGFB signaling (By similarity). {ECO:0000250|UniProtKB:P56945,
CC ECO:0000250|UniProtKB:Q61140}.
CC -!- SUBUNIT: Forms complexes in vivo with PTK2/FAK1, adapter protein CRKL
CC and LYN kinase. Can heterodimerize with NEDD9. Component of a complex
CC comprised of SH2D3C, BCAR1/CAS, and CRK (By similarity). Within the
CC complex, interacts with SH2D3C (via C-terminus), and CRK (By
CC similarity). Part of a complex comprised of PTPRA, BCAR1, BCAR3 (via
CC SH2 domain) and SRC; the formation of the complex is dependent on
CC intergrin mediated-tyrosine phosphorylation of PTPRA (By similarity).
CC Interacts with BCAR3 (via Ras-GEF domain); the interaction regulates
CC adhesion-dependent serine phosphorylation (By similarity). Interacts
CC with SMAD2 and SMAD3 (By similarity). Interacts with NPHP1 (By
CC similarity). Interacts with PTK2B/PYK2 (By similarity). Interacts (via
CC C-terminus) with SH2D3C/CHAT isoform 2 (via C-terminus) (By
CC similarity). Interacts with activated CSPG4. Interacts with BMX,
CC INPPL1/SHIP2 and PEAK1 (By similarity). Part of a collagen stimulated
CC complex involved in cell migration composed of CDC42, CRK, TNK2 and
CC BCAR1/p130cas (By similarity). Interacts with TNK2 via SH3 domains.
CC Interacts with PTK2B/PYK2 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P56945, ECO:0000250|UniProtKB:Q61140}.
CC -!- INTERACTION:
CC Q63767; P18031: PTPN1; Xeno; NbExp=5; IntAct=EBI-1176801, EBI-968788;
CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion
CC {ECO:0000250|UniProtKB:Q61140}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q61140}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q61140}. Note=Unphosphorylated form localizes in
CC the cytoplasm (By similarity). Localizes to focal adhesion sites
CC following integrin engagement (By similarity).
CC {ECO:0000250|UniProtKB:Q61140}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=Q63767-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q63767-2; Sequence=VSP_004135;
CC -!- TISSUE SPECIFICITY: Widely expressed. Higher expression in lung,
CC intestine and testis.
CC -!- DOMAIN: Contains a central domain (substrate domain) containing
CC multiple potential SH2-binding sites and a C-terminal domain containing
CC a divergent helix-loop-helix (HLH) motif. The SH2-binding sites
CC putatively bind CRK, NCK and ABL SH2 domains. The HLH motif is
CC absolutely required for the induction of pseudohyphal growth in yeast
CC and mediates heterodimerization with NEDD9.
CC -!- DOMAIN: A serine-rich region promotes activation of the serum response
CC element (SRE).
CC -!- DOMAIN: The SH3 domain is necessary for the localization of the protein
CC to focal adhesions and interacts with one proline-rich region of
CC PTK2/FAK1.
CC -!- PTM: PTK2/FAK1 activation mediates phosphorylation at the YDYVHL motif;
CC phosphorylation is most likely catalyzed by SRC family members. SRC-
CC family kinases are recruited to the phosphorylated sites and can
CC phosphorylate other tyrosine residues. Tyrosine phosphorylation is
CC triggered by integrin mediated adhesion of cells to the extracellular
CC matrix. {ECO:0000269|PubMed:7780740, ECO:0000269|PubMed:9360983}.
CC -!- PTM: Phosphorylated by SRC kinase in a EDN1- and PTK2B-mediated manner;
CC phosphorylation strengthens its interaction with BCAR3 as part of the
CC PTK2B/BCAR1/BCAR3/RAP1 signaling pathway.
CC {ECO:0000250|UniProtKB:P56945}.
CC -!- PTM: Dephosphorylated by PTPN14 at Tyr-226. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the CAS family. {ECO:0000305}.
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DR EMBL; D29766; BAA06169.1; -; mRNA.
DR EMBL; D29766; BAA06170.1; -; mRNA.
DR PIR; S46992; S46992.
DR RefSeq; NP_037063.1; NM_012931.1. [Q63767-1]
DR PDB; 1X27; X-ray; 2.70 A; I/J/K/L/M/N=759-767.
DR PDB; 1Z23; NMR; -; A=546-708.
DR PDBsum; 1X27; -.
DR PDBsum; 1Z23; -.
DR AlphaFoldDB; Q63767; -.
DR BMRB; Q63767; -.
DR SMR; Q63767; -.
DR BioGRID; 247449; 5.
DR CORUM; Q63767; -.
DR IntAct; Q63767; 7.
DR MINT; Q63767; -.
DR STRING; 10116.ENSRNOP00000039940; -.
DR iPTMnet; Q63767; -.
DR PhosphoSitePlus; Q63767; -.
DR PaxDb; Q63767; -.
DR PRIDE; Q63767; -.
DR GeneID; 25414; -.
DR KEGG; rno:25414; -.
DR UCSC; RGD:2406; rat. [Q63767-1]
DR CTD; 9564; -.
DR RGD; 2406; Bcar1.
DR eggNOG; ENOG502QQHE; Eukaryota.
DR InParanoid; Q63767; -.
DR OrthoDB; 1086228at2759; -.
DR PhylomeDB; Q63767; -.
DR Reactome; R-RNO-186763; Downstream signal transduction.
DR Reactome; R-RNO-372708; p130Cas linkage to MAPK signaling for integrins.
DR Reactome; R-RNO-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-RNO-8849471; PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
DR EvolutionaryTrace; Q63767; -.
DR PRO; PR:Q63767; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:RGD.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:RGD.
DR GO; GO:0007015; P:actin filament organization; ISS:UniProtKB.
DR GO; GO:0090527; P:actin filament reorganization; IBA:GO_Central.
DR GO; GO:0050851; P:antigen receptor-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0050853; P:B cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0060326; P:cell chemotaxis; ISO:RGD.
DR GO; GO:0016477; P:cell migration; IMP:RGD.
DR GO; GO:1990859; P:cellular response to endothelin; IPI:RGD.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; ISO:RGD.
DR GO; GO:0071732; P:cellular response to nitric oxide; IPI:RGD.
DR GO; GO:0086100; P:endothelin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0048012; P:hepatocyte growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; IMP:RGD.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:RGD.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; ISO:RGD.
DR CDD; cd12001; SH3_BCAR1; 1.
DR Gene3D; 1.20.120.830; -; 1.
DR InterPro; IPR028848; BCAR1.
DR InterPro; IPR035745; BCAR1_SH3.
DR InterPro; IPR021901; CAS_C.
DR InterPro; IPR037362; CAS_fam.
DR InterPro; IPR014928; Serine_rich_dom.
DR InterPro; IPR038319; Serine_rich_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR10654; PTHR10654; 1.
DR PANTHER; PTHR10654:SF15; PTHR10654:SF15; 1.
DR Pfam; PF12026; CAS_C; 1.
DR Pfam; PF08824; Serine_rich; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell adhesion;
KW Cell junction; Cell projection; Cytoplasm; Direct protein sequencing;
KW Phosphoprotein; Reference proteome; SH3 domain; SH3-binding.
FT CHAIN 1..968
FT /note="Breast cancer anti-estrogen resistance protein 1"
FT /id="PRO_0000064856"
FT DOMAIN 97..159
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 164..277
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 213..514
FT /note="Substrate for kinases"
FT REGION 393..416
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 503..544
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 705..756
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 844..894
FT /note="Divergent helix-loop-helix motif"
FT MOTIF 733..741
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 166..188
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 199..257
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 523..543
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 717..751
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P56945"
FT MOD_RES 226
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P56945"
FT MOD_RES 237
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56945"
FT MOD_RES 332
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q61140"
FT MOD_RES 347
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000269|PubMed:7780740"
FT MOD_RES 367
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P56945"
FT MOD_RES 390
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56945"
FT MOD_RES 460
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q61140"
FT MOD_RES 470
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q61140"
FT MOD_RES 508
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q61140"
FT MOD_RES 526
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56945"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56945"
FT MOD_RES 737
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 5..98
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_004135"
FT HELIX 554..581
FT /evidence="ECO:0007829|PDB:1Z23"
FT STRAND 591..594
FT /evidence="ECO:0007829|PDB:1Z23"
FT HELIX 599..624
FT /evidence="ECO:0007829|PDB:1Z23"
FT HELIX 634..661
FT /evidence="ECO:0007829|PDB:1Z23"
FT STRAND 664..666
FT /evidence="ECO:0007829|PDB:1Z23"
FT HELIX 671..702
FT /evidence="ECO:0007829|PDB:1Z23"
SQ SEQUENCE 968 AA; 104262 MW; E861641BFD68D377 CRC64;
MKYLVSVGAG PARRAGGLED VSWGPRVSRR PQSYRAARHV NESLPRSAFR VPAAHGASVT
PSAALGSGLP ETQPEAVCRG TEKPRFAEGC KPAASRDKNV LAKALYDNVA ESPDELSFRK
GDIMTVLERD TQGLDGWWLC SLHGRQGIVP GNRLKILVGM YDKKPAAPGP GPPATPPQPQ
PSLPQGVHTP VPPASQYSPM LPTAYQPQPD NVYLVPTPSK TQQGLYQAPG PNPQFQSPPA
KQTSTFSKQT PHHSFPSPAT DLYQVPPGPG SPAQDIYQVP PSAGTGHDIY QVPPSLDTRS
WEGTKPPAKV VVPTRVGQGY VYEASQAEQD EYDTPRHLLA PGSQDIYDVP PVRGLLPNQY
GQEVYDTPPM AVKGPNGRDP LLDVYDVPPS VEKGLPPSNH HSVYDVPPSV SKDVPDGPLL
REETYDVPPA FAKPKPFDPT RHPLILAAPP PDSPPAEDVY DVPPPAPDLY DVPPGLRRPG
PGTLYDVPRE RVLPPEVADG SVIDDGVYAV PPPAEREAPT DGKRLSASST GSTRSSQSAS
SLEVVVPGRE PLELEVAVET LARLQQGVST TVAHLLDLVG SASGPGGWRS TSEPQEPPVQ
DLKAAVAAVH GAVHELLEFA RSAVSSATHT SDRTLHAKLS RQLQKMEDVY QTLVVHGQVL
DSGRGGPGFT LDDLDRLVAC SRAVPEDAKQ LASFLHGNAS LLFRRTKAPG PGPEGSSSLH
LNPTDKASSI QSRPLPSPPK FTSQDSPDGQ YENSEGGWME DYDYVHLQGK EEFEKTQKEL
LEKGNIVRQG KGQLELQQLK QFERLEQEVS RPIDHDLANW TPAQPLVPGR TGGLGPSDRQ
LLLFYLEQCE ANLTTLTDAV DAFFTAVATN QPPKIFVAHS KFVILSAHKL VFIGDTLSRQ
AKAADVRSKV THYSNLLCDL LRGIVATTKA AALQYPSPSA AQDMVDRVKE LGHSTQQFRR
VLGQLAAA
