Human Gene BCAR1 (uc002fdv.3) Description and Page Index
  Description: Homo sapiens breast cancer anti-estrogen resistance 1 (BCAR1), transcript variant 6, mRNA.
RefSeq Summary (NM_014567): The protein encoded by this gene is a member of the Crk-associated substrate (CAS) family of scaffold proteins, characterized by the presence of multiple protein-protein interaction domains and many serine and tyrosine phosphorylation sites. The encoded protein contains a Src-homology 3 (SH3) domain, a proline-rich domain, a substrate domain which contains 15 repeat of the YxxP consensus phosphorylation motif for Src family kinases, a serine-rich domain, and a bipartite Src-binding domain, which can bind both SH2 and SH3 domains. This adaptor protein functions in multiple cellular pathways, including in cell motility, apoptosis and cell cycle control. Dysregulation of this gene can have a wide range of effects, affecting different pathways, including cardiac development, vascular smooth muscle cells, liver and kidney function, endothelial migration, and cancer. [provided by RefSeq, Sep 2017].
Transcript (Including UTRs)
   Position: hg19 chr16:75,262,928-75,285,526 Size: 22,599 Total Exon Count: 7 Strand: -
Coding Region
   Position: hg19 chr16:75,263,409-75,285,380 Size: 21,972 Coding Exon Count: 7 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr16:75,262,928-75,285,526)mRNA (may differ from genome)Protein (870 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: BCAR1_HUMAN
DESCRIPTION: RecName: Full=Breast cancer anti-estrogen resistance protein 1; AltName: Full=CRK-associated substrate; AltName: Full=Cas scaffolding protein family member 1; AltName: Full=p130cas;
FUNCTION: 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.
SUBUNIT: Forms complexes in vivo with PTK2/FAK1, adapter protein CRKL and LYN kinase. Can heterodimerize with NEDD9. Interacts with BCAR3, NPHP1 and SH2D3C (By similarity). 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.
INTERACTION: P46108:CRK; NbExp=2; IntAct=EBI-702093, EBI-886; O15357:INPPL1; NbExp=2; IntAct=EBI-702093, EBI-1384248; Q9C0H9:SRCIN1; NbExp=3; IntAct=EBI-702093, EBI-1393949; Q9QWI6:Srcin1 (xeno); NbExp=3; IntAct=EBI-702093, EBI-775592; Q04205:TNS (xeno); NbExp=2; IntAct=EBI-702093, EBI-2607590; Q68CZ2:TNS3; NbExp=8; IntAct=EBI-702093, EBI-1220488;
SUBCELLULAR LOCATION: Cell junction, focal adhesion. Cytoplasm. Note=Unphosphorylated form localizes in the cytoplasm and can move to the membrane upon tyrosine phosphorylation (By similarity).
TISSUE SPECIFICITY: 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.
DOMAIN: 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).
DOMAIN: A serine-rich region promotes activation of the serum response element (SRE).
DOMAIN: The SH3 domain is necessary for the localization of the protein to focal adhesions and interacts with one proline-rich region of PTK2/FAK11.
PTM: 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.
SIMILARITY: Belongs to the CAS family.
SIMILARITY: Contains 1 SH3 domain.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): BCAR1
CDC HuGE Published Literature: BCAR1
Positive Disease Associations: Pancreatic Neoplasms
Related Studies:
  1. Pancreatic Neoplasms
    , , . [PubMed 0]

-  MalaCards Disease Associations
  MalaCards Gene Search: BCAR1
Diseases sorted by gene-association score: estrogen resistance (28), differentiating neuroblastoma (15), breast cancer (15), nephronophthisis 1, juvenile (8), cerebral hypoxia (8), cystic kidney disease (6), nephronophthisis (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 25.24 RPKM in Brain - Cerebellum
Total median expression: 569.93 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -87.70146-0.601 Picture PostScript Text
3' UTR -215.70481-0.448 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR021901 - CAS_DUF3513
IPR014928 - Serine_rich
IPR001452 - SH3_domain
IPR013315 - Spectrin_alpha_SH3

Pfam Domains:
PF00018 - SH3 domain
PF07653 - Variant SH3 domain
PF08824 - Serine rich protein interaction domain
PF12026 - Domain of unknown function (DUF3513)
PF14604 - Variant SH3 domain

SCOP Domains:
50044 - SH3-domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1WYX
- X-ray MuPIT

3T6G
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P56945
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004871 signal transducer activity
GO:0005515 protein binding
GO:0017124 SH3 domain binding
GO:0019901 protein kinase binding

Biological Process:
GO:0001558 regulation of cell growth
GO:0007015 actin filament organization
GO:0007155 cell adhesion
GO:0007165 signal transduction
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007229 integrin-mediated signaling pathway
GO:0008283 cell proliferation
GO:0008286 insulin receptor signaling pathway
GO:0010595 positive regulation of endothelial cell migration
GO:0016477 cell migration
GO:0030335 positive regulation of cell migration
GO:0035729 cellular response to hepatocyte growth factor stimulus
GO:0042981 regulation of apoptotic process
GO:0048008 platelet-derived growth factor receptor signaling pathway
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048011 neurotrophin TRK receptor signaling pathway
GO:0048012 hepatocyte growth factor receptor signaling pathway
GO:0050851 antigen receptor-mediated signaling pathway
GO:0050852 T cell receptor signaling pathway
GO:0050853 B cell receptor signaling pathway
GO:0051301 cell division
GO:0060326 cell chemotaxis

Cellular Component:
GO:0001726 ruffle
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005925 focal adhesion
GO:0015629 actin cytoskeleton
GO:0030027 lamellipodium
GO:0030054 cell junction
GO:0005886 plasma membrane


-  Descriptions from all associated GenBank mRNAs
  AK124526 - Homo sapiens cDNA FLJ42535 fis, clone BRACE3003595, highly similar to Breast cancer anti-estrogen resistance protein 1.
AK026121 - Homo sapiens cDNA: FLJ22468 fis, clone HRC10347, highly similar to AB040024 Homo sapiens hp130Cas mRNA for adaptor protein p130Cas.
BC014402 - Homo sapiens, Similar to breast cancer anti-estrogen resistance 1, clone IMAGE:3506960, mRNA, partial cds.
BC062556 - Homo sapiens breast cancer anti-estrogen resistance 1, mRNA (cDNA clone MGC:71216 IMAGE:6427808), complete cds.
AJ242987 - Homo sapiens mRNA for breast cancer anti-estrogen resistance 1 protein (BCAR1 gene).
AK125719 - Homo sapiens cDNA FLJ43731 fis, clone TESTI1000391, highly similar to Breast cancer anti-estrogen resistance protein 1.
AK124844 - Homo sapiens cDNA FLJ42854 fis, clone BRHIP2008607, highly similar to Breast cancer anti-estrogen resistance protein 1.
AK074958 - Homo sapiens cDNA FLJ90477 fis, clone NT2RP3002738, weakly similar to Homo sapiens enhancer of filamentation (HEF1) mRNA.
AB040024 - Homo sapiens hp130Cas mRNA for adaptor protein p130Cas, complete cds.
AK124815 - Homo sapiens cDNA FLJ42825 fis, clone BRCAN2016619, highly similar to Breast cancer anti-estrogen resistance protein 1.
AK302617 - Homo sapiens cDNA FLJ55908 complete cds, highly similar to Breast cancer anti-estrogen resistance protein 1.
AF218451 - Homo sapiens Crk-associated substrate p130Cas mRNA, complete cds.
AK027608 - Homo sapiens cDNA FLJ14702 fis, clone NT2RP3000299, moderately similar to Rattus norvegicus mRNA for Crk-associated substrate, p130.
JD081968 - Sequence 62992 from Patent EP1572962.
JD109823 - Sequence 90847 from Patent EP1572962.
AK293808 - Homo sapiens cDNA FLJ56057 complete cds, highly similar to Breast cancer anti-estrogen resistance protein 1.
JD194546 - Sequence 175570 from Patent EP1572962.
JD070892 - Sequence 51916 from Patent EP1572962.
JD103369 - Sequence 84393 from Patent EP1572962.
JD382318 - Sequence 363342 from Patent EP1572962.
JD486997 - Sequence 468021 from Patent EP1572962.
JD100808 - Sequence 81832 from Patent EP1572962.
JD373052 - Sequence 354076 from Patent EP1572962.
JD459055 - Sequence 440079 from Patent EP1572962.
JD338321 - Sequence 319345 from Patent EP1572962.
JD342573 - Sequence 323597 from Patent EP1572962.
JD080004 - Sequence 61028 from Patent EP1572962.
JD269388 - Sequence 250412 from Patent EP1572962.
JD464515 - Sequence 445539 from Patent EP1572962.
AK294513 - Homo sapiens cDNA FLJ55930 complete cds, highly similar to Breast cancer anti-estrogen resistance protein 1.
AK295809 - Homo sapiens cDNA FLJ55515 complete cds, highly similar to Breast cancer anti-estrogen resistanceprotein 1.
JD118413 - Sequence 99437 from Patent EP1572962.
JD220666 - Sequence 201690 from Patent EP1572962.
JD135246 - Sequence 116270 from Patent EP1572962.
AY545071 - Homo sapiens breast cancer anti-estrogen resistance 1 (BCAR1) mRNA, complete cds, alternatively spliced.
EU831404 - Synthetic construct Homo sapiens clone HAIB:100066433; DKFZo008A0217 breast cancer anti-estrogen resistance 1 protein (BCAR1) gene, encodes complete protein.
AK314722 - Homo sapiens cDNA, FLJ95582, highly similar to Homo sapiens breast cancer anti-estrogen resistance 1 (BCAR1),mRNA.
EU831496 - Synthetic construct Homo sapiens clone HAIB:100066525; DKFZo004A0218 breast cancer anti-estrogen resistance 1 protein (BCAR1) gene, encodes complete protein.
AB587546 - Synthetic construct DNA, clone: pF1KE1059, Homo sapiens BCAR1 gene for breast cancer anti-estrogen resistance 1, without stop codon, in Flexi system.
JD335798 - Sequence 316822 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04062 - Chemokine signaling pathway
hsa04510 - Focal adhesion
hsa04670 - Leukocyte transendothelial migration
hsa04810 - Regulation of actin cytoskeleton
hsa05100 - Bacterial invasion of epithelial cells

BioCarta from NCI Cancer Genome Anatomy Project
h_integrinPathway - Integrin Signaling Pathway
h_cxcr4Pathway - CXCR4 Signaling Pathway
h_cell2cellPathway - Cell to Cell Adhesion Signaling
h_pyk2Pathway - Links between Pyk2 and Map Kinases
h_ptenPathway - PTEN dependent cell cycle arrest and apoptosis

Reactome (by CSHL, EBI, and GO)

Protein P56945 (Reactome details) participates in the following event(s):

R-HSA-372705 Recruitment of p130Cas to FADK1
R-HSA-382052 p130Cas and C3G bind PDGFR bound Crk
R-HSA-5218855 BCAR1 binds p-7Y-PTK2
R-HSA-8848713 PTK6 binds BCAR1
R-HSA-8848726 PTK6 phosphorylates BCAR1
R-HSA-372693 Phosphorylation of p130Cas by SRC-FADK1 complex
R-HSA-5218828 PTK2/SRC-1 phosphorylates BCAR1
R-HSA-372697 Crk binding to p130cas
R-HSA-5218822 CRK binds BCAR1 and or PXN
R-HSA-5218811 DOCK180:ELMO binds CRK
R-HSA-5218839 DOCK180:ELMO exchanges GTP for GDP, activating RAC1
R-HSA-372708 p130Cas linkage to MAPK signaling for integrins
R-HSA-186763 Downstream signal transduction
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-8849471 PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-354192 Integrin alphaIIb beta3 signaling
R-HSA-186797 Signaling by PDGF
R-HSA-194138 Signaling by VEGF
R-HSA-8848021 Signaling by PTK6
R-HSA-76009 Platelet Aggregation (Plug Formation)
R-HSA-9006921 Integrin signaling
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-162582 Signal Transduction
R-HSA-109582 Hemostasis

-  Other Names for This Gene
  Alternate Gene Symbols: B4DIW5, BCAR1_HUMAN, CAS, CASS1, CRKAS, NM_014567, NP_055382, P56945
UCSC ID: uc002fdv.3
RefSeq Accession: NM_014567
Protein: P56945 (aka BCAR1_HUMAN)
CCDS: CCDS10915.1, CCDS54037.1, CCDS54038.1, CCDS54041.1, CCDS54042.1, CCDS54043.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_014567.3
exon count: 7CDS single in 3' UTR: no RNA size: 3257
ORF size: 2613CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 4328.00frame shift in genome: no % Coverage: 99.48
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.