O75815 (BCAR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Breast cancer anti-estrogen resistance protein 3

Alternative name(s):
Novel SH2-containing protein 2
SH2 domain-containing protein 3B

Gene names

Name:	BCAR3
Synonyms:	NSP2, SH2D3B
ORF Names:	UNQ271/PRO308

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	825 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May act as an adapter protein and couple activated growth factor receptors to a signaling pathway that regulates the proliferation in breast cancer cells. When overexpressed, it confers anti-estrogen resistance in breast cancer cell lines. May also be regulated by cellular adhesion to extracellular matrix proteins. Ref.1
Subunit structure	Interacts with BCAR1, NEDD9, PTK2/FAK1 and PTPN1 By similarity.
Tissue specificity	Ubiquitously expressed. Found in several cancer cell lines, but not in nonmalignant breast tissue. Ref.1 Ref.2
Sequence similarities	Contains 1 Ras-GEF domain. Contains 1 SH2 domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH2 domain
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	response to drug Traceable author statement. Source: ProtInc small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	intracellular Inferred from electronic annotation. Source: InterPro
Molecular function	guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: O75815-1)

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 2 (identifier: O75815-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-324: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 825	825	Breast cancer anti-estrogen resistance protein 3		PRO_0000230284
Regions
	Domain	154 – 253	100	SH2
	Domain	548 – 818	271	Ras-GEF
	Compositional bias	479 – 482	4	Poly-Asp
Amino acid modifications
	Modified residue	32	1	Phosphoserine Ref.11
	Modified residue	83	1	Phosphoserine Ref.11
	Modified residue	130	1	Phosphothreonine Ref.7
	Modified residue	182	1	Phosphoserine Ref.8
	Modified residue	212	1	Phosphotyrosine Ref.12
	Modified residue	266	1	Phosphotyrosine Ref.10 Ref.12
	Modified residue	290	1	Phosphoserine Ref.9 Ref.11
	Modified residue	358	1	Phosphoserine Ref.11
	Modified residue	363	1	Phosphoserine Ref.11
	Modified residue	370	1	Phosphoserine By similarity
	Modified residue	375	1	Phosphoserine Ref.8 Ref.11
Natural variations
	Alternative sequence	1 – 324	324	Missing in isoform 2.		VSP_017814
	Natural variant	464	1	E → G. Corresponds to variant rs12062278 [ dbSNP | Ensembl ].		VAR_050689
	Natural variant	593	1	Q → H. Corresponds to variant rs17110107 [ dbSNP | Ensembl ].		VAR_050690

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: C55D61BB4AC7D0F2	FASTA	825	92,566
	10 20 30 40 50 60 MAAGKFASLP RNMPVNHQFP LASSMDLLSS RSPLAEHRPD AYQDVSIHGT LPRKKKGPPP 70 80 90 100 110 120 IRSCDDFSHM GTLPHSKSPR QNSPVTQDGI QESPWQDRHG ETFTFRDPHL LDPTVEYVKF 130 140 150 160 170 180 SKERHIMDRT PEKLKKELEE ELLLSSEDLR SHAWYHGRIP RQVSENLVQR DGDFLVRDSL 190 200 210 220 230 240 SSPGNFVLTC QWKNLAQHFK INRTVLRLSE AYSRVQYQFE MESFDSIPGL VRCYVGNRRP 250 260 270 280 290 300 ISQQSGAIIF QPINRTVPLR CLEEHYGTSP GQAREGSLTK GRPDVAKRLS LTMGGVQARE 310 320 330 340 350 360 QNLPRGNLLR NKEKSGSQPA CLDHMQDRRA LSLKAHQSES YLPIGCKLPP QSSGVDTSPC 370 380 390 400 410 420 PNSPVFRTGS EPALSPAVVR RVSSDARAGE ALRGSDSQLC PKPPPKPCKV PFLKVPSSPS 430 440 450 460 470 480 AWLNSEANYC ELNPAFATGC GRGAKLPSCA QGSHTELLTA KQNEAPGPRN SGVNYLILDD 490 500 510 520 530 540 DDRERPWEPA AAQMEKGQWD KGEFVTPLLE TVSSFRPNEF ESKFLPPENK PLETAMLKRA 550 560 570 580 590 600 KELFTNNDPK VIAQHVLSMD CRVARILGVS EEMRRNMGVS SGLELITLPH GHQLRLDIIE 610 620 630 640 650 660 RHNTMAIGIA VDILGCTGTL EDRAATLSKI IQVAVELKDS MGDLYSFSAL MKALEMPQIT 670 680 690 700 710 720 RLEKTWTALR HQYTQTAILY EKQLKPFSKL LHEGRESTCV PPNNVSVPLL MPLVTLMERQ 730 740 750 760 770 780 AVTFEGTDMW EKNDQSCEIM LNHLATARFM AEAADSYRMN AERILAGFQP DEEMNEICKT 790 800 810 820 EFQMRLLWGS KGAQVNQTER YEKFNQILTA LSRKLEPPPV KQAEL
	Isoform 2 [UniParc]. Checksum: 50F3B53FB4BAF59E	FASTA	501	55,745
	10 20 30 40 50 60 MQDRRALSLK AHQSESYLPI GCKLPPQSSG VDTSPCPNSP VFRTGSEPAL SPAVVRRVSS 70 80 90 100 110 120 DARAGEALRG SDSQLCPKPP PKPCKVPFLK VPSSPSAWLN SEANYCELNP AFATGCGRGA 130 140 150 160 170 180 KLPSCAQGSH TELLTAKQNE APGPRNSGVN YLILDDDDRE RPWEPAAAQM EKGQWDKGEF 190 200 210 220 230 240 VTPLLETVSS FRPNEFESKF LPPENKPLET AMLKRAKELF TNNDPKVIAQ HVLSMDCRVA 250 260 270 280 290 300 RILGVSEEMR RNMGVSSGLE LITLPHGHQL RLDIIERHNT MAIGIAVDIL GCTGTLEDRA 310 320 330 340 350 360 ATLSKIIQVA VELKDSMGDL YSFSALMKAL EMPQITRLEK TWTALRHQYT QTAILYEKQL 370 380 390 400 410 420 KPFSKLLHEG RESTCVPPNN VSVPLLMPLV TLMERQAVTF EGTDMWEKND QSCEIMLNHL 430 440 450 460 470 480 ATARFMAEAA DSYRMNAERI LAGFQPDEEM NEICKTEFQM RLLWGSKGAQ VNQTERYEKF 490 500 NQILTALSRK LEPPPVKQAE L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of BCAR3 by a random search for genes involved in antiestrogen resistance of human breast cancer cells." van Agthoven T., van Agthoven T.L.A., Dekker A., van der Spek P.J., Vreede L., Dorssers L.C.J. EMBO J. 17:2799-2808(1998) [PubMed: 9582273] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION. Tissue: Testis.
[2]	"NSP1 defines a novel family of adaptor proteins linking integrin and tyrosine kinase receptors to the c-Jun N-terminal kinase/stress-activated protein kinase signaling pathway." Lu Y., Brush J., Stewart T.A. J. Biol. Chem. 274:10047-10052(1999) [PubMed: 10187783] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Kidney.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-130, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182 AND SER-375, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-290, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-266, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32; SER-83; SER-290; SER-358; SER-363 AND SER-375, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-212 AND TYR-266, MASS SPECTROMETRY. Tissue: Mammary epithelium.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U92715 mRNA. Translation: AAC39777.1.
AF124250 mRNA. Translation: AAD28245.1.
AY358996 mRNA. Translation: AAQ89355.1.
AL359820, AL109613 Genomic DNA. Translation: CAH73975.1.
AL109613, AL359820 Genomic DNA. Translation: CAI18950.1.
CH471097 Genomic DNA. Translation: EAW73065.1.
CH471097 Genomic DNA. Translation: EAW73066.1.
BC039895 mRNA. Translation: AAH39895.1.

IPI

IPI00179053.
IPI01009616.

RefSeq

NP_003558.1. NM_003567.2.

UniGene

Hs.36958.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3T6A	X-ray	2.40	A/B/C/D	502-825	[»]

ProteinModelPortal

O75815.

SMR

O75815. Positions 147-256.

ModBase

Search...

Protein-protein interaction databases

IntAct

O75815. 3 interactions.

STRING

O75815.

PTM databases

PhosphoSite

O75815.

Proteomic databases

PRIDE

O75815.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000260502; ENSP00000260502; ENSG00000137936.
ENST00000370243; ENSP00000359263; ENSG00000137936.
ENST00000370244; ENSP00000359264; ENSG00000137936.

GeneID

8412.

KEGG

hsa:8412.

UCSC

uc001dpx.2. human.
uc001dpz.1. human.

Organism-specific databases

CTD

8412.

GeneCards

GC01M094027.

H-InvDB

HIX0000788.
HIX0029403.

HGNC

HGNC:973. BCAR3.

HPA

HPA014858.

MIM

604704. gene.

neXtProt

NX_O75815.

PharmGKB

PA25283.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13026.

GeneTree

ENSGT00390000008976.

HOGENOM

HBG402846.

HOVERGEN

HBG053174.

InParanoid

O75815.

OMA

SHMGTLP.

PhylomeDB

O75815.

Gene expression databases

ArrayExpress

O75815.

Bgee

O75815.

CleanEx

HS_BCAR3.

Genevestigator

O75815.

GermOnline

ENSG00000137936. Homo sapiens.

Family and domain databases

InterPro

IPR023578. Ras_GEF_dom.
IPR001895. RasGRF_CDC25.
IPR000980. SH2.
[Graphical view]

Gene3D

G3DSA:1.10.840.10. RasGRF_CDC25. 1 hit.
G3DSA:3.30.505.10. SH2. 1 hit.

Pfam

PF00617. RasGEF. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]

SMART

SM00147. RasGEF. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]

SUPFAM

SSF48366. Ras_GEF. 1 hit.

PROSITE

PS00720. RASGEF. False negative.
PS50009. RASGEF_CAT. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

31494.

SOURCE

Search...

Entry information

Entry name

BCAR3_HUMAN

Accession

Primary (citable) accession number: O75815
Secondary accession number(s): D3DT43, Q6UW40, Q9BR50

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 4, 2006
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.