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Protein

Breakpoint cluster region protein

Gene

BCR

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

Functioni

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.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGTPase activation, Guanine-nucleotide releasing factor, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-1839117 Signaling by cytosolic FGFR1 fusion mutants
R-HSA-194840 Rho GTPase cycle
R-HSA-5655302 Signaling by FGFR1 in disease
SignaLinkiP11274
SIGNORiP11274

Names & Taxonomyi

Protein namesi
Recommended name:
Breakpoint cluster region protein (EC:2.7.11.1)
Alternative name(s):
Renal carcinoma antigen NY-REN-26
Gene namesi
Name:BCR
Synonyms:BCR1, D22S11
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000186716.19
HGNCiHGNC:1014 BCR
MIMi151410 gene
neXtProtiNX_P11274

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

Leukemia, chronic myeloid (CML)3 Publications
The gene represented in this entry is involved in disease pathogenesis.
Disease descriptionA clonal myeloproliferative disorder of a pluripotent stem cell with a specific cytogenetic abnormality, the Philadelphia chromosome (Ph), involving myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T-lymphoid cells, but not marrow fibroblasts.
See also OMIM:608232
A chromosomal aberration involving BCR has been found in patients with 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).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi177Y → F: Abolishes interaction with FES and GRB2. 2 Publications1
Mutagenesisi1269 – 1271Missing : Abolishes interaction with PDZK1. 1 Publication3
Mutagenesisi1271V → A: Reduces interaction with PDZK1. 1 Publication1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei426 – 427Breakpoint for translocation to form BCR-ABL oncogene2

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi613
MalaCardsiBCR
MIMi608232 phenotype
OpenTargetsiENSG00000186716
Orphaneti521 Chronic myeloid leukemia
261330 Distal 22q11.2 microdeletion syndrome
99860 Precursor B-cell acute lymphoblastic leukemia
99861 Precursor T-cell acute lymphoblastic leukemia
PharmGKBiPA25321

Chemistry databases

ChEMBLiCHEMBL5146
DrugBankiDB06616 Bosutinib
DB08901 Ponatinib

Polymorphism and mutation databases

BioMutaiBCR
DMDMi143811366

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000809331 – 1271Breakpoint cluster region proteinAdd BLAST1271

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei122PhosphoserineCombined sources1
Modified residuei139PhosphoserineCombined sources1
Modified residuei177Phosphotyrosine; by HCKCombined sources1 Publication1
Modified residuei202PhosphoserineCombined sources1
Modified residuei215PhosphoserineCombined sources1
Modified residuei222PhosphoserineCombined sources1
Modified residuei236PhosphoserineBy similarity1
Modified residuei246Phosphotyrosine; by FES1 Publication1
Modified residuei356PhosphoserineCombined sources1
Modified residuei377PhosphoserineCombined sources1
Modified residuei382PhosphoserineBy similarity1
Modified residuei385PhosphothreonineBy similarity1
Modified residuei459PhosphoserineCombined sources1
Modified residuei463PhosphoserineCombined sources1
Modified residuei471Omega-N-methylarginineBy similarity1
Modified residuei473PhosphoserineCombined sources1
Modified residuei488PhosphoserineCombined sources1
Modified residuei554PhosphotyrosineCombined sources1
Modified residuei641PhosphothreonineCombined sources1
Modified residuei644PhosphotyrosineCombined sources1
Modified residuei693PhosphothreonineCombined sources1
Modified residuei894PhosphoserineCombined sources1
Modified residuei1264PhosphoserineCombined sources1

Post-translational modificationi

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 GRB2.2 Publications

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiP11274
MaxQBiP11274
PaxDbiP11274
PeptideAtlasiP11274
PRIDEiP11274
ProteomicsDBi52729
52730 [P11274-2]

PTM databases

iPTMnetiP11274
PhosphoSitePlusiP11274

Expressioni

Gene expression databases

BgeeiENSG00000186716
CleanExiHS_BCR
ExpressionAtlasiP11274 baseline and differential
GenevisibleiP11274 HS

Organism-specific databases

HPAiCAB010421
CAB018545
HPA038337

Interactioni

Subunit structurei

Homotetramer. Interacts with PDZK1. May interact with CCPG1 (By similarity). Interacts with FES/FPS, ABL1, PIK3R1 and GRB2. Interacts with HCK. Interacts with SH2D5 (PubMed:25331951).By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107083, 79 interactors
ELMiP11274
IntActiP11274, 34 interactors
MINTiP11274
STRINGi9606.ENSP00000303507

Chemistry databases

BindingDBiP11274

Structurei

Secondary structure

11271
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 14Combined sources11
Helixi28 – 64Combined sources37
Helixi492 – 521Combined sources30
Helixi524 – 531Combined sources8
Beta strandi533 – 535Combined sources3
Helixi540 – 546Combined sources7
Turni547 – 549Combined sources3
Helixi550 – 569Combined sources20
Helixi578 – 586Combined sources9
Helixi588 – 611Combined sources24
Helixi613 – 618Combined sources6
Beta strandi630 – 634Combined sources5
Helixi639 – 651Combined sources13
Helixi653 – 661Combined sources9
Helixi670 – 687Combined sources18
Beta strandi694 – 697Combined sources4
Beta strandi709 – 719Combined sources11
Beta strandi722 – 740Combined sources19
Beta strandi751 – 758Combined sources8
Helixi759 – 761Combined sources3
Beta strandi762 – 767Combined sources6
Beta strandi830 – 838Combined sources9
Beta strandi843 – 847Combined sources5
Helixi851 – 865Combined sources15
Helixi876 – 885Combined sources10
Beta strandi1268 – 1271Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K1FX-ray2.20A/B/C/D/E/F/G/H1-72[»]
2AINNMR-B1266-1271[»]
5N6RNMR-A487-702[»]
5N7EX-ray1.65B487-702[»]
5OC7X-ray1.65A/D704-893[»]
ProteinModelPortaliP11274
SMRiP11274
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11274

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini498 – 691DHPROSITE-ProRule annotationAdd BLAST194
Domaini708 – 866PHPROSITE-ProRule annotationAdd BLAST159
Domaini870 – 1002C2PROSITE-ProRule annotationAdd BLAST133
Domaini1054 – 1248Rho-GAPPROSITE-ProRule annotationAdd BLAST195

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 426KinaseAdd BLAST426
Regioni197 – 385Binding to ABL SH2-domainAdd BLAST189

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi824 – 827Poly-Leu4

Domaini

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.
The DH domain is involved in interaction with CCPG1.By similarity

Phylogenomic databases

eggNOGiKOG4269 Eukaryota
ENOG410XPGZ LUCA
GeneTreeiENSGT00920000148945
HOGENOMiHOG000006779
HOVERGENiHBG004165
InParanoidiP11274
KOiK08878
OMAiDRIMGKG
OrthoDBiEOG091G03M3
PhylomeDBiP11274
TreeFamiTF105082

Family and domain databases

CDDicd00160 RhoGEF, 1 hit
Gene3Di1.10.555.10, 1 hit
1.20.900.10, 1 hit
2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR037769 Abr/Bcr
IPR015123 Bcr-Abl_oncoprot_oligo
IPR036481 Bcr-Abl_oncoprot_oligo_sf
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR035899 DBL_dom_sf
IPR000219 DH-domain
IPR001331 GDS_CDC24_CS
IPR001849 PH_domain
IPR008936 Rho_GTPase_activation_prot
IPR000198 RhoGAP_dom
PANTHERiPTHR23182 PTHR23182, 1 hit
PfamiView protein in Pfam
PF09036 Bcr-Abl_Oligo, 1 hit
PF00168 C2, 1 hit
PF00620 RhoGAP, 1 hit
PF00621 RhoGEF, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00233 PH, 1 hit
SM00324 RhoGAP, 1 hit
SM00325 RhoGEF, 1 hit
SUPFAMiSSF48065 SSF48065, 1 hit
SSF48350 SSF48350, 1 hit
SSF69036 SSF69036, 1 hit
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS00741 DH_1, 1 hit
PS50010 DH_2, 1 hit
PS50003 PH_DOMAIN, 1 hit
PS50238 RHOGAP, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P11274-1) [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
MVDPVGFAEA WKAQFPDSEP PRMELRSVGD IEQELERCKA SIRRLEQEVN
60 70 80 90 100
QERFRMIYLQ TLLAKEKKSY DRQRWGFRRA AQAPDGASEP RASASRPQPA
110 120 130 140 150
PADGADPPPA EEPEARPDGE GSPGKARPGT ARRPGAAASG ERDDRGPPAS
160 170 180 190 200
VAALRSNFER IRKGHGQPGA DAEKPFYVNV EFHHERGLVK VNDKEVSDRI
210 220 230 240 250
SSLGSQAMQM ERKKSQHGAG SSVGDASRPP YRGRSSESSC GVDGDYEDAE
260 270 280 290 300
LNPRFLKDNL IDANGGSRPP WPPLEYQPYQ SIYVGGMMEG EGKGPLLRSQ
310 320 330 340 350
STSEQEKRLT WPRRSYSPRS FEDCGGGYTP DCSSNENLTS SEEDFSSGQS
360 370 380 390 400
SRVSPSPTTY RMFRDKSRSP SQNSQQSFDS SSPPTPQCHK RHRHCPVVVS
410 420 430 440 450
EATIVGVRKT GQIWPNDGEG AFHGDADGSF GTPPGYGCAA DRAEEQRRHQ
460 470 480 490 500
DGLPYIDDSP SSSPHLSSKG RGSRDALVSG ALESTKASEL DLEKGLEMRK
510 520 530 540 550
WVLSGILASE ETYLSHLEAL LLPMKPLKAA ATTSQPVLTS QQIETIFFKV
560 570 580 590 600
PELYEIHKEF YDGLFPRVQQ WSHQQRVGDL FQKLASQLGV YRAFVDNYGV
610 620 630 640 650
AMEMAEKCCQ ANAQFAEISE NLRARSNKDA KDPTTKNSLE TLLYKPVDRV
660 670 680 690 700
TRSTLVLHDL LKHTPASHPD HPLLQDALRI SQNFLSSINE EITPRRQSMT
710 720 730 740 750
VKKGEHRQLL KDSFMVELVE GARKLRHVFL FTDLLLCTKL KKQSGGKTQQ
760 770 780 790 800
YDCKWYIPLT DLSFQMVDEL EAVPNIPLVP DEELDALKIK ISQIKNDIQR
810 820 830 840 850
EKRANKGSKA TERLKKKLSE QESLLLLMSP SMAFRVHSRN GKSYTFLISS
860 870 880 890 900
DYERAEWREN IREQQKKCFR SFSLTSVELQ MLTNSCVKLQ TVHSIPLTIN
910 920 930 940 950
KEDDESPGLY GFLNVIVHSA TGFKQSSNLY CTLEVDSFGY FVNKAKTRVY
960 970 980 990 1000
RDTAEPNWNE EFEIELEGSQ TLRILCYEKC YNKTKIPKED GESTDRLMGK
1010 1020 1030 1040 1050
GQVQLDPQAL QDRDWQRTVI AMNGIEVKLS VKFNSREFSL KRMPSRKQTG
1060 1070 1080 1090 1100
VFGVKIAVVT KRERSKVPYI VRQCVEEIER RGMEEVGIYR VSGVATDIQA
1110 1120 1130 1140 1150
LKAAFDVNNK DVSVMMSEMD VNAIAGTLKL YFRELPEPLF TDEFYPNFAE
1160 1170 1180 1190 1200
GIALSDPVAK ESCMLNLLLS LPEANLLTFL FLLDHLKRVA EKEAVNKMSL
1210 1220 1230 1240 1250
HNLATVFGPT LLRPSEKESK LPANPSQPIT MTDSWSLEVM SQVQVLLYFL
1260 1270
QLEAIPAPDS KRQSILFSTE V
Length:1,271
Mass (Da):142,819
Last modified:April 3, 2007 - v2
Checksum:i4BF66FA1E9D205FE
GO
Isoform 2 (identifier: P11274-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:1,227
Mass (Da):137,729
Checksum:iEFEE4915DE3FE893
GO

Sequence cautioni

The sequence BAE06073 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti287M → I in CAA68676 (PubMed:3285291).Curated1
Sequence conflicti418G → D in CAA68676 (PubMed:3285291).Curated1
Sequence conflicti483E → K in CAA68676 (PubMed:3285291).Curated1
Sequence conflicti560F → S in CAA68676 (PubMed:3285291).Curated1
Sequence conflicti690E → D (PubMed:2407300).Curated1
Sequence conflicti733D → E in CAA26441 (PubMed:3107980).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041883400S → P in a bladder transitional cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041884413I → M1 PublicationCorresponds to variant dbSNP:rs56321828Ensembl.1
Natural variantiVAR_051983558K → T. Corresponds to variant dbSNP:rs4437065Ensembl.1
Natural variantiVAR_041885752D → E1 PublicationCorresponds to variant dbSNP:rs12484731Ensembl.1
Natural variantiVAR_031552796N → S5 PublicationsCorresponds to variant dbSNP:rs140504Ensembl.1
Natural variantiVAR_041886910Y → C1 PublicationCorresponds to variant dbSNP:rs35537221Ensembl.1
Natural variantiVAR_041887949V → I1 PublicationCorresponds to variant dbSNP:rs2229038EnsemblClinVar.1
Natural variantiVAR_0315531037E → K1 PublicationCorresponds to variant dbSNP:rs776552570Ensembl.1
Natural variantiVAR_0418881091V → M1 PublicationCorresponds to variant dbSNP:rs778229520Ensembl.1
Natural variantiVAR_0418891096T → A1 PublicationCorresponds to variant dbSNP:rs745459086Ensembl.1
Natural variantiVAR_0418901104A → G1 PublicationCorresponds to variant dbSNP:rs11558696Ensembl.1
Natural variantiVAR_0418911106D → N1 PublicationCorresponds to variant dbSNP:rs879255379EnsemblClinVar.1
Natural variantiVAR_0315541127T → M. Corresponds to variant dbSNP:rs35812689Ensembl.1
Natural variantiVAR_0418921149A → T1 PublicationCorresponds to variant dbSNP:rs200099830Ensembl.1
Natural variantiVAR_0418931161E → K1 Publication1
Natural variantiVAR_0418941187K → E1 Publication1
Natural variantiVAR_0418951189V → M1 PublicationCorresponds to variant dbSNP:rs55816482Ensembl.1
Natural variantiVAR_0418961204A → G1 PublicationCorresponds to variant dbSNP:rs56265970Ensembl.1
Natural variantiVAR_0418971235W → R1 PublicationCorresponds to variant dbSNP:rs55719322Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_024352961 – 1004Missing in isoform 2. 1 PublicationAdd BLAST44

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13806.1 [P11274-1]
CCDS13807.1 [P11274-2]
PIRiA26664 TVHUA2
A91064 TVHUBR
RefSeqiNP_004318.3, NM_004327.3 [P11274-1]
NP_067585.2, NM_021574.2 [P11274-2]
UniGeneiHs.517461
Hs.715409

Genome annotation databases

EnsembliENST00000305877; ENSP00000303507; ENSG00000186716 [P11274-1]
ENST00000359540; ENSP00000352535; ENSG00000186716 [P11274-2]
GeneIDi613
KEGGihsa:613
UCSCiuc002zww.4 human [P11274-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiBCR_HUMAN
AccessioniPrimary (citable) accession number: P11274
Secondary accession number(s): P78501
, Q12842, Q4LE80, Q6NZI3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: April 3, 2007
Last modified: June 20, 2018
This is version 216 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, Reference proteome

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