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Protein

Breast cancer anti-estrogen resistance protein 1

Gene

BCAR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion. Implicated in induction of cell migration. Overexpression confers antiestrogen resistance on breast cancer cells.2 Publications

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB-KW
  • signal transducer activity Source: ProtInc

GO - Biological processi

  • actin filament organization Source: UniProtKB
  • antigen receptor-mediated signaling pathway Source: UniProtKB
  • B cell receptor signaling pathway Source: UniProtKB
  • cell adhesion Source: UniProtKB-KW
  • cell chemotaxis Source: BHF-UCL
  • cell division Source: UniProtKB
  • cell migration Source: UniProtKB
  • cell proliferation Source: ProtInc
  • cellular response to hepatocyte growth factor stimulus Source: BHF-UCL
  • epidermal growth factor receptor signaling pathway Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • hepatocyte growth factor receptor signaling pathway Source: BHF-UCL
  • insulin receptor signaling pathway Source: UniProtKB
  • integrin-mediated signaling pathway Source: UniProtKB
  • neurotrophin TRK receptor signaling pathway Source: UniProtKB
  • platelet-derived growth factor receptor signaling pathway Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of endothelial cell migration Source: BHF-UCL
  • regulation of apoptotic process Source: UniProtKB
  • regulation of cell growth Source: UniProtKB
  • T cell receptor signaling pathway Source: UniProtKB
  • vascular endothelial growth factor receptor signaling pathway Source: BHF-UCL

Keywordsi

Biological processCell adhesion

Enzyme and pathway databases

ReactomeiR-HSA-186763. Downstream signal transduction.
R-HSA-372708. p130Cas linkage to MAPK signaling for integrins.
R-HSA-4420097. VEGFA-VEGFR2 Pathway.
R-HSA-8849471. PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
SignaLinkiP56945.
SIGNORiP56945.

Names & Taxonomyi

Protein namesi
Recommended name:
Breast cancer anti-estrogen resistance protein 1
Alternative name(s):
CRK-associated substrate
Cas scaffolding protein family member 1
p130cas
Gene namesi
Name:BCAR1
Synonyms:CAS, CASS1, CRKAS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:971. BCAR1.

Subcellular locationi

GO - Cellular componenti

  • actin cytoskeleton Source: Ensembl
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • focal adhesion Source: BHF-UCL
  • lamellipodium Source: Ensembl
  • ruffle Source: UniProtKB

Keywords - Cellular componenti

Cell junction, Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi9564.
OpenTargetsiENSG00000050820.
PharmGKBiPA25281.

Polymorphism and mutation databases

BioMutaiBCAR1.
DMDMi288558806.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000648541 – 870Breast cancer anti-estrogen resistance protein 1Add BLAST870

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine1 Publication1
Modified residuei128Phosphotyrosine; by SRC1 Publication1
Modified residuei134PhosphoserineCombined sources1
Modified residuei139PhosphoserineCombined sources1 Publication1
Modified residuei234PhosphotyrosineBy similarity1
Modified residuei249Phosphotyrosine; by ABL1By similarity1
Modified residuei269PhosphothreonineCombined sources1
Modified residuei292PhosphoserineCombined sources1
Modified residuei362PhosphotyrosineBy similarity1
Modified residuei372PhosphotyrosineBy similarity1
Modified residuei410PhosphotyrosineBy similarity1
Modified residuei428PhosphoserineCombined sources1
Modified residuei437Phosphoserine1 Publication1
Modified residuei639PhosphoserineCombined sources1 Publication1

Post-translational modificationi

PTK2/FAK1 activation mediates phosphorylation at the YDYVHL motif; phosphorylation is most likely catalyzed by SRC family members. SRC-family kinases are recruited to the phosphorylated sites and can phosphorylate other tyrosine residues. Tyrosine phosphorylation is triggered by integrin-mediated adhesion of cells to the extracellular matrix.4 Publications
Dephosphorylated by PTPN14 at Tyr-128.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP56945.
MaxQBiP56945.
PaxDbiP56945.
PeptideAtlasiP56945.
PRIDEiP56945.

PTM databases

iPTMnetiP56945.
PhosphoSitePlusiP56945.

Expressioni

Tissue specificityi

Widely expressed with an abundant expression in the testis. Low level of expression seen in the liver, thymus, and peripheral blood leukocytes. The protein has been detected in a B-cell line.

Gene expression databases

BgeeiENSG00000050820.
CleanExiHS_BCAR1.
ExpressionAtlasiP56945. baseline and differential.
GenevisibleiP56945. HS.

Organism-specific databases

HPAiCAB000443.
HPA042282.

Interactioni

Subunit structurei

Forms complexes in vivo with PTK2/FAK1, adapter protein CRKL and LYN kinase. Can heterodimerize with NEDD9. Interacts with BCAR3, the interaction regulates adhesion-dependent serine phosphorylation. Interacts with NPHP1 and SH2D3C. Interacts with activated CSPG4. Interacts with BMX, INPPL1/SHIP2 and PEAK1. Part of a collagen-stimulated complex involved in cell migration made of CDC42, CRK, TNK2 and BCAR1/p130cas. Interacts with TNK2 via SH3 domains. Interacts with PTK2B/PYK2.8 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB-KW

Protein-protein interaction databases

BioGridi114934. 68 interactors.
DIPiDIP-33855N.
IntActiP56945. 46 interactors.
MINTiMINT-1505539.
STRINGi9606.ENSP00000391669.

Structurei

Secondary structure

1870
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 12Combined sources8
Beta strandi29 – 34Combined sources6
Helixi37 – 39Combined sources3
Beta strandi43 – 48Combined sources6
Beta strandi51 – 56Combined sources6
Helixi57 – 59Combined sources3
Beta strandi60 – 68Combined sources9
Helixi740 – 770Combined sources31
Helixi775 – 801Combined sources27
Helixi806 – 835Combined sources30
Helixi840 – 870Combined sources31

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WYXX-ray1.14A/B3-71[»]
3T6GX-ray2.50B/D645-870[»]
ProteinModelPortaliP56945.
SMRiP56945.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP56945.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini3 – 65SH3PROSITE-ProRule annotationAdd BLAST63

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni115 – 416Substrate for kinasesBy similarityAdd BLAST302
Regioni746 – 796Divergent helix-loop-helix motifAdd BLAST51

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi635 – 643SH3-bindingSequence analysis9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi74 – 87Pro-richAdd BLAST14
Compositional biasi422 – 614Ser-richAdd BLAST193

Domaini

Contains a central domain (substrate domain) containing multiple potential SH2-binding sites and a C-terminal domain containing a divergent helix-loop-helix (HLH) motif. The SH2-binding sites putatively bind CRK, NCK and ABL1 SH2 domains. The HLH motif is absolutely required for the induction of pseudohyphal growth in yeast and mediates heterodimerization with NEDD9 (By similarity).By similarity
A serine-rich region promotes activation of the serum response element (SRE).
The SH3 domain is necessary for the localization of the protein to focal adhesions and interacts with one proline-rich region of PTK2/FAK11.

Sequence similaritiesi

Belongs to the CAS family.Curated

Keywords - Domaini

SH3 domain, SH3-binding

Phylogenomic databases

eggNOGiENOG410IEDD. Eukaryota.
ENOG410ZSUM. LUCA.
GeneTreeiENSGT00490000043324.
HOGENOMiHOG000261698.
HOVERGENiHBG004354.
InParanoidiP56945.
KOiK05726.
OMAiLANMPDY.
OrthoDBiEOG091G0RVA.
PhylomeDBiP56945.
TreeFamiTF328782.

Family and domain databases

InterProiView protein in InterPro
IPR028848. BCAR1.
IPR021901. CAS_C.
IPR014928. Serine_rich.
IPR001452. SH3_domain.
IPR013315. Spectrin_alpha_SH3.
PANTHERiPTHR10654:SF24. PTHR10654:SF24. 1 hit.
PfamiView protein in Pfam
PF12026. DUF3513. 1 hit.
PF08824. Serine_rich. 1 hit.
PF00018. SH3_1. 1 hit.
PRINTSiPR00452. SH3DOMAIN.
PR01887. SPECTRNALPHA.
SMARTiView protein in SMART
SM00326. SH3. 1 hit.
SUPFAMiSSF50044. SSF50044. 1 hit.
PROSITEiView protein in PROSITE
PS50002. SH3. 1 hit.

Sequences (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P56945-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MNHLNVLAKA LYDNVAESPD ELSFRKGDIM TVLEQDTQGL DGWWLCSLHG
60 70 80 90 100
RQGIVPGNRL KILVGMYDKK PAGPGPGPPA TPAQPQPGLH APAPPASQYT
110 120 130 140 150
PMLPNTYQPQ PDSVYLVPTP SKAQQGLYQV PGPSPQFQSP PAKQTSTFSK
160 170 180 190 200
QTPHHPFPSP ATDLYQVPPG PGGPAQDIYQ VPPSAGMGHD IYQVPPSMDT
210 220 230 240 250
RSWEGTKPPA KVVVPTRVGQ GYVYEAAQPE QDEYDIPRHL LAPGPQDIYD
260 270 280 290 300
VPPVRGLLPS QYGQEVYDTP PMAVKGPNGR DPLLEVYDVP PSVEKGLPPS
310 320 330 340 350
NHHAVYDVPP SVSKDVPDGP LLREETYDVP PAFAKAKPFD PARTPLVLAA
360 370 380 390 400
PPPDSPPAED VYDVPPPAPD LYDVPPGLRR PGPGTLYDVP RERVLPPEVA
410 420 430 440 450
DGGVVDSGVY AVPPPAEREA PAEGKRLSAS STGSTRSSQS ASSLEVAGPG
460 470 480 490 500
REPLELEVAV EALARLQQGV SATVAHLLDL AGSAGATGSW RSPSEPQEPL
510 520 530 540 550
VQDLQAAVAA VQSAVHELLE FARSAVGNAA HTSDRALHAK LSRQLQKMED
560 570 580 590 600
VHQTLVAHGQ ALDAGRGGSG ATLEDLDRLV ACSRAVPEDA KQLASFLHGN
610 620 630 640 650
ASLLFRRTKA TAPGPEGGGT LHPNPTDKTS SIQSRPLPSP PKFTSQDSPD
660 670 680 690 700
GQYENSEGGW MEDYDYVHLQ GKEEFEKTQK ELLEKGSITR QGKSQLELQQ
710 720 730 740 750
LKQFERLEQE VSRPIDHDLA NWTPAQPLAP GRTGGLGPSD RQLLLFYLEQ
760 770 780 790 800
CEANLTTLTN AVDAFFTAVA TNQPPKIFVA HSKFVILSAH KLVFIGDTLS
810 820 830 840 850
RQAKAADVRS QVTHYSNLLC DLLRGIVATT KAAALQYPSP SAAQDMVERV
860 870
KELGHSTQQF RRVLGQLAAA
Length:870
Mass (Da):93,372
Last modified:February 9, 2010 - v2
Checksum:iB81EC3430049E795
GO
Isoform 2 (identifier: P56945-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MNHL → MLTHRPQEAEQRGRTPGPSFEW

Note: No experimental confirmation available.
Show »
Length:888
Mass (Da):95,469
Checksum:i4CA6EC5C8EFE3DA6
GO
Isoform 3 (identifier: P56945-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     304-304: A → AVSKCQGNARARLRLWGVW

Show »
Length:888
Mass (Da):95,454
Checksum:iFF81642D11EB93AC
GO
Isoform 4 (identifier: P56945-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MNHL → MQGK
     64-211: Missing.

Note: No experimental confirmation available.
Show »
Length:722
Mass (Da):77,731
Checksum:i2537ED6C3BEBE512
GO
Isoform 5 (identifier: P56945-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MNHL → ME

Note: No experimental confirmation available.
Show »
Length:868
Mass (Da):93,137
Checksum:iDB6B70B2AB1926CD
GO
Isoform 6 (identifier: P56945-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MNHL → MPAKPFLSSVLLSWKVLDFSGPGPQGTGQPCSCGHWAEGQGGPPEPAGGP

Note: No experimental confirmation available.
Show »
Length:916
Mass (Da):97,877
Checksum:i3A5FDEB4BA15527B
GO
Isoform 7 (identifier: P56945-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MNHL → MHCPGEAPLAAPRPTPKDPCLR

Note: No experimental confirmation available.
Show »
Length:888
Mass (Da):95,216
Checksum:iCD3BA8494536FC76
GO
Isoform 8 (identifier: P56945-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MNHL → MSVP

Note: No experimental confirmation available.
Show »
Length:870
Mass (Da):93,291
Checksum:i2262F3718326A675
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti63L → S in BAB55230 (PubMed:14702039).Curated1
Sequence conflicti236I → T in AAF27527 (Ref. 2) Curated1
Sequence conflicti254V → I in BAG54099 (PubMed:14702039).Curated1
Sequence conflicti349A → G in AAF27527 (Ref. 2) Curated1
Sequence conflicti363D → Y in AAF27527 (Ref. 2) Curated1
Sequence conflicti385T → A in AAS48631 (Ref. 4) Curated1
Sequence conflicti428S → P in BAB55230 (PubMed:14702039).Curated1
Sequence conflicti471S → G in BAB55230 (PubMed:14702039).Curated1
Sequence conflicti600N → S in AAS48631 (Ref. 4) Curated1
Sequence conflicti700Q → R in BAH13763 (PubMed:14702039).Curated1
Sequence conflicti714P → L in BAG54099 (PubMed:14702039).Curated1
Sequence conflicti740D → G in AAS48631 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05897076P → S4 PublicationsCorresponds to variant dbSNP:rs1035539Ensembl.1
Natural variantiVAR_035798407S → T in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_057820491R → L. Corresponds to variant dbSNP:rs16957558Ensembl.1
Natural variantiVAR_057821558H → R. Corresponds to variant dbSNP:rs16957552Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0435591 – 4MNHL → MLTHRPQEAEQRGRTPGPSF EW in isoform 2. 1 Publication4
Alternative sequenceiVSP_0461271 – 4MNHL → MQGK in isoform 4. 1 Publication4
Alternative sequenceiVSP_0467481 – 4MNHL → ME in isoform 5. 1 Publication4
Alternative sequenceiVSP_0467491 – 4MNHL → MPAKPFLSSVLLSWKVLDFS GPGPQGTGQPCSCGHWAEGQ GGPPEPAGGP in isoform 6. 1 Publication4
Alternative sequenceiVSP_0467501 – 4MNHL → MHCPGEAPLAAPRPTPKDPC LR in isoform 7. 1 Publication4
Alternative sequenceiVSP_0467511 – 4MNHL → MSVP in isoform 8. 1 Publication4
Alternative sequenceiVSP_04612864 – 211Missing in isoform 4. 1 PublicationAdd BLAST148
Alternative sequenceiVSP_045355304A → AVSKCQGNARARLRLWGVW in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ242987 mRNA. Translation: CAB75875.2.
AF218451 mRNA. Translation: AAF27527.1.
AB040024 mRNA. Translation: BAA92711.1.
AY545071 mRNA. Translation: AAS48631.1.
AK027608 mRNA. Translation: BAB55230.1.
AK124815 mRNA. Translation: BAG54099.1.
AK293808 mRNA. Translation: BAG57215.1.
AK294513 mRNA. Translation: BAG57726.1.
AK295809 mRNA. Translation: BAG58627.1.
AK302617 mRNA. Translation: BAH13763.1.
AC009078 Genomic DNA. No translation available.
CCDSiCCDS10915.1. [P56945-1]
CCDS54037.1. [P56945-5]
CCDS54038.1. [P56945-3]
CCDS54039.1. [P56945-4]
CCDS54040.1. [P56945-6]
CCDS54041.1. [P56945-8]
CCDS54042.1. [P56945-2]
CCDS54043.1. [P56945-7]
RefSeqiNP_001164185.1. NM_001170714.1. [P56945-6]
NP_001164186.1. NM_001170715.1. [P56945-7]
NP_001164187.1. NM_001170716.1. [P56945-2]
NP_001164188.1. NM_001170717.1. [P56945-3]
NP_001164189.1. NM_001170718.1. [P56945-8]
NP_001164190.1. NM_001170719.1. [P56945-5]
NP_001164191.1. NM_001170720.1. [P56945-4]
NP_001164192.1. NM_001170721.1.
NP_055382.2. NM_014567.3. [P56945-1]
XP_016879386.1. XM_017023897.1. [P56945-6]
UniGeneiHs.479747.

Genome annotation databases

EnsembliENST00000162330; ENSP00000162330; ENSG00000050820. [P56945-1]
ENST00000393420; ENSP00000377072; ENSG00000050820. [P56945-3]
ENST00000393422; ENSP00000377074; ENSG00000050820. [P56945-7]
ENST00000418647; ENSP00000391669; ENSG00000050820. [P56945-6]
ENST00000420641; ENSP00000392708; ENSG00000050820. [P56945-2]
ENST00000535626; ENSP00000440370; ENSG00000050820. [P56945-4]
ENST00000538440; ENSP00000443841; ENSG00000050820. [P56945-8]
ENST00000542031; ENSP00000440415; ENSG00000050820. [P56945-5]
GeneIDi9564.
KEGGihsa:9564.
UCSCiuc002fdv.4. human. [P56945-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiBCAR1_HUMAN
AccessioniPrimary (citable) accession number: P56945
Secondary accession number(s): B3KWD7
, B4DEV4, B4DGB5, B4DIW5, B7Z7X7, E9PCL5, E9PCV2, F5GXA2, F5GXV6, F5H7Z0, F8WA69, Q6QEF7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: February 9, 2010
Last modified: July 5, 2017
This is version 175 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families