P11274 (BCR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Breakpoint cluster region protein
EC=2.7.11.1

Alternative name(s):
Renal carcinoma antigen NY-REN-26

Gene names

Name:	BCR
Synonyms:	BCR1, D22S11

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	1271 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. Displays serine/threonine kinase activity. Ref.13 Ref.15
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Homotetramer. Interacts with PDZK1. May interact with CCPG1 By similarity. Interacts with FES/FPS, ABL1, PIK3R1 and GRB2. Interacts with HCK. Ref.14 Ref.16 Ref.20 Ref.21 Ref.29
Domain	The region involved in binding to ABL1 SH2-domain is rich in serine residues and needs to be Ser/Thr phosphorylated prior to SH2 binding. This region is essential for the activation of the ABL1 tyrosine kinase and transforming potential of the chimeric BCR-ABL oncogene. Ref.14 The DH domain is involved in interaction with CCPG1 By similarity. Ref.14
Post-translational modification	Autophosphorylated. Phosphorylated by FES/FPS on tyrosine residues, leading to down-regulation of the BCR kinase activity. Phosphorylation at Tyr-177 by HCK is important for interaction with GRB2. Ref.16 Ref.18 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27
Involvement in disease	Note=A chromosomal aberration involving BCR is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with ABL1. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
Sequence similarities	Contains 1 C2 domain. Contains 1 DH (DBL-homology) domain. Contains 1 PH domain. Contains 1 Rho-GAP domain.
Sequence caution	The sequence BAE06073.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Ligand	ATP-binding Nucleotide-binding
Molecular function	GTPase activation Guanine-nucleotide releasing factor Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW Rho guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: InterPro protein serine/threonine kinase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P11274-1)

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: P11274-2)

The sequence of this isoform differs from the canonical sequence as follows:
     961-1004: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1271

1271

Breakpoint cluster region protein

PRO_0000080933

Regions

Domain

498 – 691

194

DH

Domain

708 – 866

159

PH

Domain

870 – 1002

133

C2

Domain

1054 – 1248

195

Rho-GAP

Region

1 – 426

426

Kinase

Region

197 – 385

189

Binding to ABL SH2-domain

Compositional bias

824 – 827

4

Poly-Leu

Sites

Site

426 – 427

2

Breakpoint for translocation to form BCR-ABL oncogene

Amino acid modifications

Modified residue

122

1

Phosphoserine Ref.25

Modified residue

177

1

Phosphotyrosine; by HCK Ref.16 Ref.18 Ref.23 Ref.27

Modified residue

236

1

Phosphoserine By similarity

Modified residue

246

1

Phosphotyrosine; by FES Ref.20

Modified residue

310

1

Phosphothreonine Ref.18

Modified residue

459

1

Phosphoserine Ref.18 Ref.22 Ref.24 Ref.26 Ref.27

Modified residue

463

1

Phosphoserine Ref.18 Ref.26

Modified residue

591

1

Phosphotyrosine Ref.18

Modified residue

644

1

Phosphotyrosine Ref.18

Modified residue

1264

1

Phosphoserine Ref.19 Ref.27

Natural variations

Alternative sequence

961 – 1004

44

Missing in isoform 2.

VSP_024352

Natural variant

400

1

S → P in a bladder transitional cell carcinoma sample; somatic mutation. Ref.30

VAR_041883

Natural variant

413

1

I → M. Ref.30
Corresponds to variant rs56321828 [ dbSNP | Ensembl ].

VAR_041884

Natural variant

558

1

K → T.
Corresponds to variant rs4437065 [ dbSNP | Ensembl ].

VAR_051983

Natural variant

752

1

D → E. Ref.30
Corresponds to variant rs12484731 [ dbSNP | Ensembl ].

VAR_041885

Natural variant

796

1

N → S. Ref.1 Ref.3 Ref.4 Ref.11 Ref.30
Corresponds to variant rs140504 [ dbSNP | Ensembl ].

VAR_031552

Natural variant

910

1

Y → C. Ref.30
Corresponds to variant rs35537221 [ dbSNP | Ensembl ].

VAR_041886

Natural variant

949

1

V → I. Ref.30
Corresponds to variant rs2229038 [ dbSNP | Ensembl ].

VAR_041887

Natural variant

1037

1

E → K. Ref.30
Corresponds to variant rs16999516 [ dbSNP | Ensembl ].

VAR_031553

Natural variant

1091

1

V → M. Ref.30

VAR_041888

Natural variant

1096

1

T → A. Ref.30

VAR_041889

Natural variant

1104

1

A → G. Ref.30

VAR_041890

Natural variant

1106

1

D → N. Ref.30

VAR_041891

Natural variant

1127

1

T → M.
Corresponds to variant rs35812689 [ dbSNP | Ensembl ].

VAR_031554

Natural variant

1149

1

A → T. Ref.30

VAR_041892

Natural variant

1161

1

E → K. Ref.30

VAR_041893

Natural variant

1187

1

K → E. Ref.30

VAR_041894

Natural variant

1189

1

V → M. Ref.30
Corresponds to variant rs55816482 [ dbSNP | Ensembl ].

VAR_041895

Natural variant

1204

1

A → G. Ref.30
Corresponds to variant rs56265970 [ dbSNP | Ensembl ].

VAR_041896

Natural variant

1235

1

W → R. Ref.30
Corresponds to variant rs55719322 [ dbSNP | Ensembl ].

VAR_041897

Experimental info

Mutagenesis

177

1

Y → F: Abolishes interaction with FES and GRB2. Ref.16 Ref.20

Mutagenesis

1269 – 1271

3

Missing: Abolishes interaction with PDZK1. Ref.21

Mutagenesis

1271

1

V → A: Reduces interaction with PDZK1. Ref.21

Sequence conflict

287

1

M → I in CAA68676. Ref.1

Sequence conflict

418

1

G → D in CAA68676. Ref.1

Sequence conflict

483

1

E → K in CAA68676. Ref.1

Sequence conflict

560

1

F → S in CAA68676. Ref.1

Sequence conflict

690

1

E → D Ref.11

Sequence conflict

733

1

D → E in CAA26441. Ref.4

Secondary structure

1

.

.

.

.

.

1271

Helix Strand Turn

Details...

Helix

4 – 14

11

Helix

28 – 64

37

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 3, 2007. Version 2. Checksum: 4BF66FA1E9D205FE	FASTA	1,271	142,819
	10 20 30 40 50 60 MVDPVGFAEA WKAQFPDSEP PRMELRSVGD IEQELERCKA SIRRLEQEVN QERFRMIYLQ 70 80 90 100 110 120 TLLAKEKKSY DRQRWGFRRA AQAPDGASEP RASASRPQPA PADGADPPPA EEPEARPDGE 130 140 150 160 170 180 GSPGKARPGT ARRPGAAASG ERDDRGPPAS VAALRSNFER IRKGHGQPGA DAEKPFYVNV 190 200 210 220 230 240 EFHHERGLVK VNDKEVSDRI SSLGSQAMQM ERKKSQHGAG SSVGDASRPP YRGRSSESSC 250 260 270 280 290 300 GVDGDYEDAE LNPRFLKDNL IDANGGSRPP WPPLEYQPYQ SIYVGGMMEG EGKGPLLRSQ 310 320 330 340 350 360 STSEQEKRLT WPRRSYSPRS FEDCGGGYTP DCSSNENLTS SEEDFSSGQS SRVSPSPTTY 370 380 390 400 410 420 RMFRDKSRSP SQNSQQSFDS SSPPTPQCHK RHRHCPVVVS EATIVGVRKT GQIWPNDGEG 430 440 450 460 470 480 AFHGDADGSF GTPPGYGCAA DRAEEQRRHQ DGLPYIDDSP SSSPHLSSKG RGSRDALVSG 490 500 510 520 530 540 ALESTKASEL DLEKGLEMRK WVLSGILASE ETYLSHLEAL LLPMKPLKAA ATTSQPVLTS 550 560 570 580 590 600 QQIETIFFKV PELYEIHKEF YDGLFPRVQQ WSHQQRVGDL FQKLASQLGV YRAFVDNYGV 610 620 630 640 650 660 AMEMAEKCCQ ANAQFAEISE NLRARSNKDA KDPTTKNSLE TLLYKPVDRV TRSTLVLHDL 670 680 690 700 710 720 LKHTPASHPD HPLLQDALRI SQNFLSSINE EITPRRQSMT VKKGEHRQLL KDSFMVELVE 730 740 750 760 770 780 GARKLRHVFL FTDLLLCTKL KKQSGGKTQQ YDCKWYIPLT DLSFQMVDEL EAVPNIPLVP 790 800 810 820 830 840 DEELDALKIK ISQIKNDIQR EKRANKGSKA TERLKKKLSE QESLLLLMSP SMAFRVHSRN 850 860 870 880 890 900 GKSYTFLISS DYERAEWREN IREQQKKCFR SFSLTSVELQ MLTNSCVKLQ TVHSIPLTIN 910 920 930 940 950 960 KEDDESPGLY GFLNVIVHSA TGFKQSSNLY CTLEVDSFGY FVNKAKTRVY RDTAEPNWNE 970 980 990 1000 1010 1020 EFEIELEGSQ TLRILCYEKC YNKTKIPKED GESTDRLMGK GQVQLDPQAL QDRDWQRTVI 1030 1040 1050 1060 1070 1080 AMNGIEVKLS VKFNSREFSL KRMPSRKQTG VFGVKIAVVT KRERSKVPYI VRQCVEEIER 1090 1100 1110 1120 1130 1140 RGMEEVGIYR VSGVATDIQA LKAAFDVNNK DVSVMMSEMD VNAIAGTLKL YFRELPEPLF 1150 1160 1170 1180 1190 1200 TDEFYPNFAE GIALSDPVAK ESCMLNLLLS LPEANLLTFL FLLDHLKRVA EKEAVNKMSL 1210 1220 1230 1240 1250 1260 HNLATVFGPT LLRPSEKESK LPANPSQPIT MTDSWSLEVM SQVQVLLYFL QLEAIPAPDS 1270 KRQSILFSTE V
	Isoform 2 [UniParc]. Checksum: EFEE4915DE3FE893	FASTA	1,227	137,729
	10 20 30 40 50 60 MVDPVGFAEA WKAQFPDSEP PRMELRSVGD IEQELERCKA SIRRLEQEVN QERFRMIYLQ 70 80 90 100 110 120 TLLAKEKKSY DRQRWGFRRA AQAPDGASEP RASASRPQPA PADGADPPPA EEPEARPDGE 130 140 150 160 170 180 GSPGKARPGT ARRPGAAASG ERDDRGPPAS VAALRSNFER IRKGHGQPGA DAEKPFYVNV 190 200 210 220 230 240 EFHHERGLVK VNDKEVSDRI SSLGSQAMQM ERKKSQHGAG SSVGDASRPP YRGRSSESSC 250 260 270 280 290 300 GVDGDYEDAE LNPRFLKDNL IDANGGSRPP WPPLEYQPYQ SIYVGGMMEG EGKGPLLRSQ 310 320 330 340 350 360 STSEQEKRLT WPRRSYSPRS FEDCGGGYTP DCSSNENLTS SEEDFSSGQS SRVSPSPTTY 370 380 390 400 410 420 RMFRDKSRSP SQNSQQSFDS SSPPTPQCHK RHRHCPVVVS EATIVGVRKT GQIWPNDGEG 430 440 450 460 470 480 AFHGDADGSF GTPPGYGCAA DRAEEQRRHQ DGLPYIDDSP SSSPHLSSKG RGSRDALVSG 490 500 510 520 530 540 ALESTKASEL DLEKGLEMRK WVLSGILASE ETYLSHLEAL LLPMKPLKAA ATTSQPVLTS 550 560 570 580 590 600 QQIETIFFKV PELYEIHKEF YDGLFPRVQQ WSHQQRVGDL FQKLASQLGV YRAFVDNYGV 610 620 630 640 650 660 AMEMAEKCCQ ANAQFAEISE NLRARSNKDA KDPTTKNSLE TLLYKPVDRV TRSTLVLHDL 670 680 690 700 710 720 LKHTPASHPD HPLLQDALRI SQNFLSSINE EITPRRQSMT VKKGEHRQLL KDSFMVELVE 730 740 750 760 770 780 GARKLRHVFL FTDLLLCTKL KKQSGGKTQQ YDCKWYIPLT DLSFQMVDEL EAVPNIPLVP 790 800 810 820 830 840 DEELDALKIK ISQIKNDIQR EKRANKGSKA TERLKKKLSE QESLLLLMSP SMAFRVHSRN 850 860 870 880 890 900 GKSYTFLISS DYERAEWREN IREQQKKCFR SFSLTSVELQ MLTNSCVKLQ TVHSIPLTIN 910 920 930 940 950 960 KEDDESPGLY GFLNVIVHSA TGFKQSSNLY CTLEVDSFGY FVNKAKTRVY RDTAEPNWNE 970 980 990 1000 1010 1020 LDPQALQDRD WQRTVIAMNG IEVKLSVKFN SREFSLKRMP SRKQTGVFGV KIAVVTKRER 1030 1040 1050 1060 1070 1080 SKVPYIVRQC VEEIERRGME EVGIYRVSGV ATDIQALKAA FDVNNKDVSV MMSEMDVNAI 1090 1100 1110 1120 1130 1140 AGTLKLYFRE LPEPLFTDEF YPNFAEGIAL SDPVAKESCM LNLLLSLPEA NLLTFLFLLD 1150 1160 1170 1180 1190 1200 HLKRVAEKEA VNKMSLHNLA TVFGPTLLRP SEKESKLPAN PSQPITMTDS WSLEVMSQVQ 1210 1220 VLLYFLQLEA IPAPDSKRQS ILFSTEV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"bcr genes and transcripts." Lifshitz B., Fainstein E., Marcelle C., Shtivelman E., Amson R., Gale R.P., Canaani E. Oncogene 2:113-117(1988) [PubMed: 3285291] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT SER-796.
[2]	"Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal translocation." Chissoe S.L., Bodenteich A., Wang Y.-F., Wang Y.-P., Burian D., Clifton S.W., Crabtree J., Freeman A., Iyer K., Jian L., Ma Y., McLaury H.-J., Pan H.-Q., Sarhan O.H., Toth S., Wang Z., Zhang G., Heisterkamp N., Groffen J., Roe B.A. Genomics 27:67-82(1995) [PubMed: 7665185] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Preparation of a set of expression-ready clones of mammalian long cDNAs encoding large proteins by the ORF trap cloning method." Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R., Okazaki N., Koga H., Nagase T., Ohara O. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT SER-796. Tissue: Brain.
[4]	"cDNA sequence for human bcr, the gene that translocates to the abl oncogene in chronic myeloid leukaemia." Hariharan I.K., Adams J.M. EMBO J. 6:115-119(1987) [PubMed: 3107980] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-872, VARIANT SER-796.
[5]	"Overlapping cDNA clones define the complete coding region for the P210c-abl gene product associated with chronic myelogenous leukemia cells containing the Philadelphia chromosome." Mes-Masson A.-M., McLaughlin J., Daley G.Q., Paskind M., Witte O.N. Proc. Natl. Acad. Sci. U.S.A. 83:9768-9772(1986) [PubMed: 3540951] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-693.
[6]	Erratum Mes-Masson A.M., McLaughlin J., Daley G.Q., Paskind M., Witte O.N. Proc. Natl. Acad. Sci. U.S.A. 84:2507-2507(1987) Cited for: SEQUENCE REVISION.
[7]	"Structural organization of the bcr gene and its role in the Ph' translocation." Heisterkamp N., Stam K., Groffen J., de Klein A., Grosveld G. Nature 315:758-761(1985) [PubMed: 2989703] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 683-1271 (ISOFORM 1).
[8]	"Unique organization of the human BCR gene promoter." Zhu Q.S., Heisterkamp N., Groffen J. Nucleic Acids Res. 18:7119-7125(1990) [PubMed: 2263470] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-46 AND 275-426.
[9]	"A new fused transcript in Philadelphia chromosome positive acute lymphocytic leukaemia." Fainstein E., Marcelle C., Rosner A., Canaani E., Gale R.P., Dreazen O., Smith S.D., Croce C.M. Nature 330:386-388(1987) [PubMed: 2825022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 56-426.
[10]	"Alternative 5' end of the bcr-abl transcript in chronic myelogenous leukemia." Romero P., Beran M., Shtalrid M., Andersson B., Talpaz M., Blick M. Oncogene 4:93-98(1989) [PubMed: 2915904] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 362-438, ALTERNATIVE SPLICING.
[11]	"Chronic myeloid leukemia may be associated with several bcr-abl transcripts including the acute lymphoid leukemia-type 7 kb transcript." Selleri L., von Lindern M., Hermans A., Meijer D., Torelli G., Grosveld G. Blood 75:1146-1153(1990) [PubMed: 2407300] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 670-842, VARIANT SER-796.
[12]	"Characterization of the BCR promoter in Philadelphia chromosome-positive and -negative cell lines." Shah N.P., Witte O.N., Denny C.T. Mol. Cell. Biol. 11:1854-1860(1991) [PubMed: 1900918] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-4.
[13]	"Bcr encodes a GTPase-activating protein for p21rac." Diekmann D., Brill S., Garrett M.D., Totty N., Hsuan J., Monfries C., Hall C., Lim L., Hall A. Nature 351:400-402(1991) [PubMed: 1903516] [Abstract] Cited for: FUNCTION.
[14]	"BCR sequences essential for transformation by the BCR-ABL oncogene bind to the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner." Pendergast A.M., Muller A.J., Havlik M.H., Maru Y., Witte O.N. Cell 66:161-171(1991) [PubMed: 1712671] [Abstract] Cited for: INTERACTION WITH ABL1 SH2-DOMAIN.
[15]	"The BCR gene encodes a novel serine/threonine kinase activity within a single exon." Maru Y., Witte O.N. Cell 67:459-468(1991) [PubMed: 1657398] [Abstract] Cited for: FUNCTION AS PROTEIN KINASE.
[16]	"The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent mechanism and phosphorylates the Grb2-binding site of Bcr." Warmuth M., Bergmann M., Priess A., Hauslmann K., Emmerich B., Hallek M. J. Biol. Chem. 272:33260-33270(1997) [PubMed: 9407116] [Abstract] Cited for: PHOSPHORYLATION AT TYR-177 BY HCK, MUTAGENESIS OF TYR-177, INTERACTION WITH HCK AND GRB2.
[17]	"Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed: 10508479] [Abstract] Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma.
[18]	"Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry." Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C. Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003) [PubMed: 12522270] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-177; THR-310; SER-459; SER-463; TYR-591 AND TYR-644, MASS SPECTROMETRY.
[19]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed: 15144186] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1264, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[20]	"The c-Fes tyrosine kinase cooperates with the breakpoint cluster region protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent manner." Laurent C.E., Smithgall T.E. Exp. Cell Res. 299:188-198(2004) [PubMed: 15302586] [Abstract] Cited for: INTERACTION WITH FES/FPS; ABL1; PIK3R1 AND GRB2, MUTAGENESIS OF TYR-177, PHOSPHORYLATION AT TYR-246.
[21]	"Bcr (breakpoint cluster region) protein binds to PDZ-domains of scaffold protein PDZK1 and vesicle coat protein Mint3." Malmberg E.K., Andersson C.X., Gentzsch M., Chen J.H., Mengos A., Cui L., Hansson G.C., Riordan J.R. J. Cell Sci. 117:5535-5541(2004) [PubMed: 15494376] [Abstract] Cited for: INTERACTION WITH PDZK1, MUTAGENESIS OF 1269-THR--GLU-1271 AND VAL-1271.
[22]	"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 SER-459, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[23]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-177, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[24]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-459, MASS SPECTROMETRY. Tissue: Platelet.
[25]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[26]	"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-459 AND SER-463, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[27]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-177; SER-459 AND SER-1264, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[28]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]	"Structure of the Bcr-Abl oncoprotein oligomerization domain." Zhao X., Ghaffari S., Lodish H., Malashkevich V.N., Kim P.S. Nat. Struct. Biol. 9:117-120(2002) [PubMed: 11780146] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 3-72, HOMOTETRAMERIZATION.
[30]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] PRO-400; MET-413; GLU-752; SER-796; CYS-910; ILE-949; LYS-1037; MET-1091; ALA-1096; GLY-1104; ASN-1106; THR-1149; LYS-1161; GLU-1187; MET-1189; GLY-1204 AND ARG-1235.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y00661 mRNA. Translation: CAA68676.1.
U07000 Genomic DNA. Translation: AAB60388.1.
AB209991 mRNA. Translation: BAE06073.1. Different initiation.
X02596 mRNA. Translation: CAA26441.1.
M15025 Genomic DNA. Translation: AAA35594.1.
X52828 Genomic DNA. Translation: CAA37010.1.
X52829 Genomic DNA. Translation: CAA37011.1.
X14676 mRNA. Translation: CAA32806.1.
M64437 mRNA. No translation available.

IPI

IPI00004497.
IPI00472302.

PIR

TVHUA2. A26664.
TVHUBR. A91064.

RefSeq

NP_004318.3. NM_004327.3.
NP_067585.2. NM_021574.2.

UniGene

Hs.517461.
Hs.715409.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1K1F	X-ray	2.20	A/B/C/D/E/F/G/H	1-72	[»]
2AIN	NMR	-	B	1266-1271	[»]

ProteinModelPortal

P11274.

SMR

P11274. Positions 1-67, 497-697, 706-766, 910-1008, 1048-1254.

ModBase

Search...

Protein-protein interaction databases

IntAct

P11274. 12 interactions.

MINT

MINT-1207264.

STRING

P11274.

PTM databases

PhosphoSite

P11274.

Polymorphism databases

DMDM

143811366.

Proteomic databases

PRIDE

P11274.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000305877; ENSP00000303507; ENSG00000186716.

GeneID

613.

KEGG

hsa:613.

UCSC

uc002zww.1. human.
uc002zwx.1. human.

Organism-specific databases

CTD

613.

GeneCards

GC22P023521.

HGNC

HGNC:1014. BCR.

HPA

HPA038337.

MIM

151410. gene.
608232. phenotype.

neXtProt

NX_P11274.

Orphanet

521. Chronic myeloid leukemia.
567. Monosomy 22q11.
99860. Precursor B-cell acute lymphoblastic leukemia.
99861. Precursor T-cell acute lymphoblastic leukemia.

PharmGKB

PA25321.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18137.

HOGENOM

HBG446960.

HOVERGEN

HBG004165.

InParanoid

P11274.

OMA

NDIQREK.

OrthoDB

EOG4FFD11.

PhylomeDB

P11274.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P11274.

Bgee

P11274.

CleanEx

HS_BCR.

Genevestigator

P11274.

GermOnline

ENSG00000186716. Homo sapiens.

Family and domain databases

InterPro

IPR015123. Bcr-Abl_oncoprot_oligo.
IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR018029. C2_membr_targeting.
IPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR011993. PH_type.
IPR001849. Pleckstrin_homology.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 2 hits.
G3DSA:1.10.555.10. RhoGAP. 1 hit.
G3DSA:1.20.900.10. RhoGEF. 1 hit.

KO

K08878.

Pfam

PF09036. Bcr-Abl_Oligo. 1 hit.
PF00168. C2. 1 hit.
PF00169. PH. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]

SMART

SM00239. C2. 1 hit.
SM00233. PH. 1 hit.
SM00324. RhoGAP. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]

SUPFAM

SSF69036. Bcr-Abl_oncoprot_oligo. 1 hit.
SSF49562. C2_CaLB. 1 hit.
SSF48065. DH-domain. 1 hit.
SSF48350. Rho_GAP. 1 hit.

PROSITE

PS50004. C2. 1 hit.
PS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50238. RHOGAP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

2485.

SOURCE

Search...

Entry information

Entry name

BCR_HUMAN

Accession

Primary (citable) accession number: P11274
Secondary accession number(s): P78501 , Q12842, Q4LE80, Q6NZI3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	April 3, 2007
Last modified:	January 25, 2012
This is version 146 of the entry and version 2 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.