Q61140 (BCAR1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Breast cancer anti-estrogen resistance protein 1

Alternative name(s):
CRK-associated substrate
p130cas

Gene names

Name:	Bcar1
Synonyms:	Cas, Crkas

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	874 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion. Implicated in induction of cell migration By similarity. Has been shown to be essential in cardiovascular development during embryogenesis.
Subunit structure	Forms complexes in vivo with PTK2/FAK1, adapter protein CRKL and LYN kinase. Can heterodimerize with NEDD9. Interacts with activated CSPG4. Interacts with BMX, INPPL1/SHIP2 and PEAK1 By similarity. Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas By similarity. Interacts with BCAR3, the interaction regulates adhesion-dependent serine phosphorylation. Interacts with NPHP1, PTK2B/PYK2 and SH2D3C. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8
Subcellular location	Cell junction › focal adhesion By similarity. Cytoplasm By similarity. Note: Unphosphorylated form localizes in the cytoplasm and can move to the membrane upon tyrosine phosphorylation By similarity.
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 ABL SH2 domains. The HLH motif is absolutely required for the induction of pseudohyphal growth in yeast and mediates heterodimerization with NEDD9. A serine-rich region promotes activation of the serum response element (SRE) By similarity. The SH3 domain is necessary for the localization of the protein to focal adhesions and interacts with one proline-rich region of PTK2/FAK1.
Post-translational modification	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 By similarity. Dephosphorylated by PTPN14 at Tyr-132 By similarity.
Sequence similarities	Belongs to the CAS family. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	SH3 domain SH3-binding
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB G-protein coupled receptor signaling pathway Inferred from direct assay PubMed 9083073. Source: UniProtKB actin filament organization Inferred from sequence or structural similarity. Source: UniProtKB antigen receptor-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cell chemotaxis Inferred from electronic annotation. Source: Ensembl cell migration Inferred from sequence or structural similarity. Source: UniProtKB cellular response to hepatocyte growth factor stimulus Inferred from electronic annotation. Source: Ensembl epidermal growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB hepatocyte growth factor receptor signaling pathway Inferred from electronic annotation. Source: Ensembl insulin receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB integrin-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB neurotrophin TRK receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB platelet-derived growth factor receptor signaling pathway Inferred from direct assay PubMed 9083073. Source: UniProtKB positive regulation of cell migration Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of endothelial cell migration Inferred from electronic annotation. Source: Ensembl vascular endothelial growth factor receptor signaling pathway Inferred from electronic annotation. Source: Ensembl
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB focal adhesion Inferred from sequence or structural similarity. Source: UniProtKB lamellipodium Inferred from direct assay PubMed 15728191. Source: MGI plasma membrane Inferred from electronic annotation. Source: Ensembl ruffle Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	protein binding Inferred from physical interaction Ref.1. Source: UniProtKB signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Nphp1	Q9QY53	2	EBI-77088,EBI-77230
Ptk2	P34152	3	EBI-77088,EBI-77070
PTPN1	P18031	5	EBI-77088,EBI-968788	From a different organism.
Srcin1	Q9QWI6	2	EBI-77088,EBI-775592

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Cas-B (identifier: Q61140-1)

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.

Isoform Cas-A (identifier: Q61140-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 874	874	Breast cancer anti-estrogen resistance protein 1		PRO_0000064855
Regions
	Domain	6 – 26	21	SH3
	Region	119 – 420	302	Substrate for kinases By similarity
	Region	750 – 800	51	Divergent helix-loop-helix motif
	Motif	639 – 647	9	SH3-binding Potential
	Compositional bias	74 – 87	14	Pro-rich
	Compositional bias	426 – 618	193	Ser-rich
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine By similarity
	Modified residue	132	1	Phosphotyrosine Ref.9
	Modified residue	143	1	Phosphoserine By similarity
	Modified residue	253	1	Phosphotyrosine; by ABL1 By similarity
	Modified residue	273	1	Phosphothreonine By similarity
	Modified residue	296	1	Phosphoserine By similarity
	Modified residue	366	1	Phosphotyrosine Ref.9
	Modified residue	376	1	Phosphotyrosine Ref.9
	Modified residue	414	1	Phosphotyrosine Ref.9
	Modified residue	432	1	Phosphoserine By similarity
	Modified residue	441	1	Phosphoserine By similarity
	Modified residue	643	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 4	4	MTVP → MKYL in isoform Cas-A.		VSP_004134
Experimental info
	Sequence conflict	72	1	V → A in AAA93381. Ref.1
	Sequence conflict	72	1	V → A in AAA93248. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Cas-B [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 81E56BC7AD87B095	FASTA	874	94,285
	10 20 30 40 50 60 MTVPNVLAKA LYDNVAESPD ELSFRKGDIM TVLERDTQGL DGWWLCSLHG RQGIVPGNRL 70 80 90 100 110 120 KILVGMYDKK PVGPGPGPPA TPPQPQPSLP QGVHAPVPPA SQYSPMLPTA YQPQSDNVYL 130 140 150 160 170 180 VPTPSKTQQG LYQAPGPNPQ FQSPPAKQTS TFSKQTPHHS FPSPATDLYQ VPPGPGSPAQ 190 200 210 220 230 240 DIYQVPPSAG IGHDIYQVPP SLDTRGWEGT KPPAKVVVPT RVGQGYVYEA AQTEQDEYDT 250 260 270 280 290 300 PRHLLAPGPQ DIYDVPPVRG LLPNQYGQEV YDTPPMAVKG PNGRDPLLDV YDVPPSVEKG 310 320 330 340 350 360 LLSSSHHSVY DVPPSVSKDV PDGPLLREET YDVPPAFAKP KPFDPTRHPL ILAAPPPDSP 370 380 390 400 410 420 AAEDVYDVPP PAPDLYDVPP GLRRPGPGTL YDVPRERVLP PEVADGSVVD DGVYAVPPPA 430 440 450 460 470 480 EREAPTDGKR LSASSTGSTR SSQSASSLEV VVPGREPLEL EVAVESLARL QQGVSTTVAH 490 500 510 520 530 540 LLDLVGSASG PGGWRGTSEP QEPPAQDLKA AVAAVHGAVH ELLEFARGAV SNATHTSDRT 550 560 570 580 590 600 LHAKLSRQLQ KMEDVYQTLV VHGQVLDSGR GSPGFTPEDL DRLVACSRAV PEDAKQLASF 610 620 630 640 650 660 LHGNASLLFR RTKAPGPGPE GSSSLHPNPT DKASSIQSRP LPSPPKFTSQ DSPDGQYENS 670 680 690 700 710 720 EGGWMEDYDY VHLQGKEEFE KTQKELLERG NIMRQGKGQL ELQQLKQFER LEQEVSRPID 730 740 750 760 770 780 HDLANWTPAQ PLVPGRTGGL GPSDRQLLLF YLEQCEANLT TLTDAVDAFF TAVATNQPPK 790 800 810 820 830 840 IFVAHSKFVI LSAHKLVFIG DTLSRQAKAA DVRSQVTHYS NLLCDLLRGI VATTKAAALQ 850 860 870 YPSPSAAQDM VDRVKELGHS TQQFRRVLGQ LAAA
	Isoform Cas-A [UniParc]. Checksum: 25B8F5D1D61CC8B1	FASTA	874	94,392
	10 20 30 40 50 60 MKYLNVLAKA LYDNVAESPD ELSFRKGDIM TVLERDTQGL DGWWLCSLHG RQGIVPGNRL 70 80 90 100 110 120 KILVGMYDKK PVGPGPGPPA TPPQPQPSLP QGVHAPVPPA SQYSPMLPTA YQPQSDNVYL 130 140 150 160 170 180 VPTPSKTQQG LYQAPGPNPQ FQSPPAKQTS TFSKQTPHHS FPSPATDLYQ VPPGPGSPAQ 190 200 210 220 230 240 DIYQVPPSAG IGHDIYQVPP SLDTRGWEGT KPPAKVVVPT RVGQGYVYEA AQTEQDEYDT 250 260 270 280 290 300 PRHLLAPGPQ DIYDVPPVRG LLPNQYGQEV YDTPPMAVKG PNGRDPLLDV YDVPPSVEKG 310 320 330 340 350 360 LLSSSHHSVY DVPPSVSKDV PDGPLLREET YDVPPAFAKP KPFDPTRHPL ILAAPPPDSP 370 380 390 400 410 420 AAEDVYDVPP PAPDLYDVPP GLRRPGPGTL YDVPRERVLP PEVADGSVVD DGVYAVPPPA 430 440 450 460 470 480 EREAPTDGKR LSASSTGSTR SSQSASSLEV VVPGREPLEL EVAVESLARL QQGVSTTVAH 490 500 510 520 530 540 LLDLVGSASG PGGWRGTSEP QEPPAQDLKA AVAAVHGAVH ELLEFARGAV SNATHTSDRT 550 560 570 580 590 600 LHAKLSRQLQ KMEDVYQTLV VHGQVLDSGR GSPGFTPEDL DRLVACSRAV PEDAKQLASF 610 620 630 640 650 660 LHGNASLLFR RTKAPGPGPE GSSSLHPNPT DKASSIQSRP LPSPPKFTSQ DSPDGQYENS 670 680 690 700 710 720 EGGWMEDYDY VHLQGKEEFE KTQKELLERG NIMRQGKGQL ELQQLKQFER LEQEVSRPID 730 740 750 760 770 780 HDLANWTPAQ PLVPGRTGGL GPSDRQLLLF YLEQCEANLT TLTDAVDAFF TAVATNQPPK 790 800 810 820 830 840 IFVAHSKFVI LSAHKLVFIG DTLSRQAKAA DVRSQVTHYS NLLCDLLRGI VATTKAAALQ 850 860 870 YPSPSAAQDM VDRVKELGHS TQQFRRVLGQ LAAA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas." Polte T.R., Hanks S.K. Proc. Natl. Acad. Sci. U.S.A. 92:10678-10682(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS CAS-A AND CAS-B), INTERACTION WITH PTK2/FAK1. Tissue: Embryo.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Placenta.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6.
[4]	"AND-34, a novel p130Cas-binding thymic stromal cell protein regulated by adhesion and inflammatory cytokines." Cai D., Clayton L.K., Smolyar A., Lerner A. J. Immunol. 163:2104-2112(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BCAR3.
[5]	"Crk-associated substrate p130(Cas) interacts with nephrocystin and both proteins localize to cell-cell contacts of polarized epithelial cells." Donaldson J.C., Dempsey P.J., Reddy S., Bouton A.H., Coffey R.J., Hanks S.K. Exp. Cell Res. 256:168-178(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NPHP1.
[6]	"p130Cas regulates the activity of AND-34, a novel Ral, Rap1, and R-Ras guanine nucleotide exchange factor." Gotoh T., Cai D., Tian X., Feig L.A., Lerner A. J. Biol. Chem. 275:30118-30123(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BCAR3.
[7]	"Chat, a Cas/HEF1-associated adaptor protein that integrates multiple signaling pathways." Sakakibara A., Hattori S. J. Biol. Chem. 275:6404-6410(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SH2D3C.
[8]	"A novel hematopoietic adaptor protein, Chat-H, positively regulates T cell receptor-mediated interleukin-2 production by Jurkat cells." Sakakibara A., Hattori S., Nakamura S., Katagiri T. J. Biol. Chem. 278:6012-6017(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SH2D3C. Tissue: Spleen.
[9]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-132; TYR-366; TYR-376 AND TYR-414, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Brain.
[11]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-253, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic fibroblast.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U48853 mRNA. Translation: AAA93381.1. U28151 mRNA. Translation: AAA93248.1. AK145863 mRNA. Translation: BAE26705.1. BC057578 mRNA. Translation: AAH57578.1.
CCDS	CCDS52675.1. [Q61140-1]
RefSeq	NP_001185768.1. NM_001198839.1. [Q61140-2] NP_034084.2. NM_009954.3. [Q61140-1]
UniGene	Mm.3758.
3D structure databases
ProteinModelPortal	Q61140.
SMR	Q61140. Positions 5-71, 454-614, 743-874.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	198886. 6 interactions.
IntAct	Q61140. 14 interactions.
MINT	MINT-100691.
PTM databases
PhosphoSite	Q61140.
Proteomic databases
MaxQB	Q61140.
PaxDb	Q61140.
PRIDE	Q61140.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000166232; ENSMUSP00000129584; ENSMUSG00000031955. [Q61140-1]
GeneID	12927.
KEGG	mmu:12927.
UCSC	uc009nmt.2. mouse. [Q61140-2] uc009nmu.2. mouse. [Q61140-1]
Organism-specific databases
CTD	9564.
MGI	MGI:108091. Bcar1.
Phylogenomic databases
eggNOG	NOG82196.
GeneTree	ENSGT00490000043324.
HOGENOM	HOG000261698.
HOVERGEN	HBG004354.
KO	K05726.
OMA	FAKAKPF.
OrthoDB	EOG7QRQTD.
TreeFam	TF328782.
Gene expression databases
Bgee	Q61140.
CleanEx	MM_BCAR1.
Genevestigator	Q61140.
Family and domain databases
InterPro	IPR028848. BCAR1. IPR021901. CAS_DUF3513. IPR014928. Serine_rich. IPR001452. SH3_domain. IPR013315. Spectrin_alpha_SH3. [Graphical view]
PANTHER	PTHR10654:SF5. PTHR10654:SF5. 1 hit.
Pfam	PF12026. DUF3513. 1 hit. PF08824. Serine_rich. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00452. SH3DOMAIN. PR01887. SPECTRNALPHA.
SMART	SM00326. SH3. 1 hit. [Graphical view]
SUPFAM	SSF50044. SSF50044. 1 hit.
PROSITE	PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	282588.
PRO	Q61140.
SOURCE	Search...

Entry information

Entry name

BCAR1_MOUSE

Accession

Primary (citable) accession number: Q61140
Secondary accession number(s): Q60869, Q6PFF9

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	July 27, 2011
Last modified:	July 9, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program