Description: Homo sapiens breakpoint cluster region (BCR), transcript variant 1, mRNA. RefSeq Summary (NM_004327): A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the BCR gene. The translocation produces a fusion protein which is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint. Although the BCR-ABL fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The unregulated tyrosine kinase activity of BCR-ABL1 contributes to the immortality of leukaemic cells. The BCR protein has serine/threonine kinase activity and is a GTPase-activating protein for p21rac and other kinases. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2020]. Transcript (Including UTRs) Position: hg19 chr22:23,522,552-23,660,224 Size: 137,673 Total Exon Count: 23 Strand: + Coding Region Position: hg19 chr22:23,523,148-23,657,709 Size: 134,562 Coding Exon Count: 23
ID:BCR_HUMAN DESCRIPTION: RecName: Full=Breakpoint cluster region protein; EC=2.7.11.1; AltName: Full=Renal carcinoma antigen NY-REN-26; 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. SUBUNIT: Homotetramer. Interacts with PDZK1. May interact with CCPG1 (By similarity). Interacts with FES/FPS, ABL1, PIK3R1 and GRB2. Interacts with HCK. INTERACTION: Q9H2K2:TNKS2; NbExp=3; IntAct=EBI-712838, EBI-4398527; 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. DOMAIN: The DH domain is involved in interaction with CCPG1 (By similarity). PTM: 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. 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). SIMILARITY: Contains 1 C2 domain. SIMILARITY: Contains 1 DH (DBL-homology) domain. SIMILARITY: Contains 1 PH domain. SIMILARITY: Contains 1 Rho-GAP domain. SEQUENCE CAUTION: Sequence=BAE06073.1; Type=Erroneous initiation; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/BCR.html";
Blood Vessels Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903301]
In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.
Body Height Daniel F Gudbjartsson et al. Nature genetics 2008, Many sequence variants affecting diversity of adult human height., Nature genetics.
[PubMed 18391951]
depressive disorder, major; bipolar disorder Hashimoto, R. et al. 2005, The Breakpoint Cluster Region Gene on Chromosome 22q11 is Associated with Bipolar Disorder, Biological psychiatry. 2005 May;57(10):1097-102.
[PubMed 15866548]
Our results suggest that genetic variations in the BCR gene could confer susceptibility to bipolar disorder and major depressive disorder.
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.
ModBase Predicted Comparative 3D Structure on P11274
Front
Top
Side
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.
Biological Process: GO:0002692 negative regulation of cellular extravasation GO:0003014 renal system process GO:0006468 protein phosphorylation GO:0007165 signal transduction GO:0007420 brain development GO:0016310 phosphorylation GO:0018108 peptidyl-tyrosine phosphorylation GO:0030036 actin cytoskeleton organization GO:0030336 negative regulation of cell migration GO:0032496 response to lipopolysaccharide GO:0035023 regulation of Rho protein signal transduction GO:0035556 intracellular signal transduction GO:0042472 inner ear morphogenesis GO:0043114 regulation of vascular permeability GO:0043314 negative regulation of neutrophil degranulation GO:0043547 positive regulation of GTPase activity GO:0046777 protein autophosphorylation GO:0048008 platelet-derived growth factor receptor signaling pathway GO:0048872 homeostasis of number of cells GO:0050728 negative regulation of inflammatory response GO:0050766 positive regulation of phagocytosis GO:0050885 neuromuscular process controlling balance GO:0051056 regulation of small GTPase mediated signal transduction GO:0051171 regulation of nitrogen compound metabolic process GO:0051726 regulation of cell cycle GO:0060216 definitive hemopoiesis GO:0060268 negative regulation of respiratory burst GO:0060313 negative regulation of blood vessel remodeling GO:0065002 intracellular protein transmembrane transport GO:0071222 cellular response to lipopolysaccharide GO:2000378 negative regulation of reactive oxygen species metabolic process
Y00661 - Human bcr mRNA (break point cluster gene). X02596 - Human mRNA for bcr (breakpoint cluster region) gene in Philadelphia chromosome. BC066122 - Homo sapiens breakpoint cluster region, mRNA (cDNA clone IMAGE:30341883). JD211267 - Sequence 192291 from Patent EP1572962. AB209991 - Homo sapiens mRNA for BCR variant protein, clone: aj01345. AB384354 - Synthetic construct DNA, clone: pF1KSDB0005, Homo sapiens BCR gene for breakpoint cluster region protein, complete cds, without stop codon, in Flexi system. EU216070 - Homo sapiens BCR/ABL fusion protein isoform Y4 (BCR/ABL fusion) mRNA, complete cds. EU216064 - Homo sapiens BCR/ABL fusion protein isoform X7 (BCR/ABL fusion) mRNA, complete cds. EU216062 - Homo sapiens BCR/ABL fusion protein isoform X5 (BCR/ABL fusion) mRNA, complete cds. EU216059 - Homo sapiens BCR/ABL fusion protein isoform X2 (BCR/ABL fusion) mRNA, complete cds. EU216061 - Homo sapiens BCR/ABL fusion protein isoform X4 (BCR/ABL fusion) mRNA, complete cds. EU216068 - Homo sapiens BCR/ABL fusion protein isoform Y2 (BCR/ABL fusion) mRNA, complete cds. EU216067 - Homo sapiens BCR/ABL fusion protein isoform Y1 (BCR/ABL fusion) mRNA, complete cds. EU216065 - Homo sapiens BCR/ABL fusion protein isoform X8 (BCR/ABL fusion) mRNA, complete cds. AM491362 - Homo sapiens partial mRNA for bcr-abl1 e6a2 chimeric protein. X14676 - Human bcr-abl mRNA fragment (clone 10b). AJ298916 - Homo sapiens partial mRNA for BCR/FGFR1 chimaeric fusion protein. HQ622706 - Homo sapiens BCR-ABL1 e8a2 variant (BCR-ABL1) mRNA, partial cds. DQ912588 - Homo sapiens BCR/ABL fusion protein e1a5 (BCR/ABL fusion) mRNA, partial cds, alternatively spliced. M17542 - Human bcr/abl protein gene (product of translocation t(22q11; 9q34)), exons 1 and 2. X14677 - Human bcr-abl mRNA 5' fragment (clone 8a). X14675 - Human bcr-abl mRNA 5' fragment (clone 3c). AK303241 - Homo sapiens cDNA FLJ58654 complete cds, highly similar to Breakpoint cluster region protein (EC 2.7.11.1). AK128501 - Homo sapiens cDNA FLJ46653 fis, clone TRACH3005173. DQ912589 - Homo sapiens BCR/ABL fusion protein e13a5 (BCR/ABL fusion) mRNA, partial cds, alternatively spliced. DQ912590 - Homo sapiens BCR/ABL fusion protein e14a5 (BCR/ABL fusion) mRNA, partial cds, alternatively spliced. M64437 - Human BCR mRNA, 5' end. JD443520 - Sequence 424544 from Patent EP1572962. JC506674 - Sequence 42 from Patent EP2733220. JC737786 - Sequence 42 from Patent WO2014075939. JC506688 - Sequence 56 from Patent EP2733220. JC737800 - Sequence 56 from Patent WO2014075939. JC506666 - Sequence 34 from Patent EP2733220. JC737778 - Sequence 34 from Patent WO2014075939. JC506661 - Sequence 29 from Patent EP2733220. JC737773 - Sequence 29 from Patent WO2014075939. JD406875 - Sequence 387899 from Patent EP1572962. JD461506 - Sequence 442530 from Patent EP1572962. JD406253 - Sequence 387277 from Patent EP1572962. JD208476 - Sequence 189500 from Patent EP1572962. X06418 - Human bcr-abl mRNA of acute lymphocytic leukaemia (ALL) patients. EU216072 - Homo sapiens BCR/ABL fusion protein isoform Y6 (BCR/ABL fusion) mRNA, complete cds. EU216058 - Homo sapiens BCR/ABL fusion protein isoform X1 (BCR/ABL fusion) mRNA, complete cds. EU216063 - Homo sapiens BCR/ABL fusion protein isoform X6 (BCR/ABL fusion) mRNA, complete cds. EU216069 - Homo sapiens BCR/ABL fusion protein isoform Y3 (BCR/ABL fusion) mRNA, complete cds. M19730 - Human acute lymphocytic leukemia (ALL) BCR-ABL mRNA encoding P185-ALL-ABL protein. DQ898313 - Homo sapiens isolate e1a4 BCR/ABL fusion protein (BCR/ABL fusion) mRNA, partial cds, alternatively spliced. S72479 - BCR...ABL {e1/a3 junction, translocation breakpoint} [human, Japanese ALL patient 3, bone marow, mononuclear cells, mRNA Mutant, 3 genes, 131 nt]. AF251769 - Homo sapiens bcr/abl e1-a3 chimeric fusion protein (BCR/ABLe1-a3) mRNA, partial cds. AB742170 - Homo sapiens mRNA for BCR/FGFR1 chimera protein, partial cds. AY536245 - Homo sapiens isolate BCRcml2L1I072001 breakpoint cluster region protein (BCR) mRNA, partial cds. AY536247 - Homo sapiens isolate BCRcml2k10I072001 breakpoint cluster region protein (BCR) mRNA, partial cds. AY536248 - Homo sapiens isolate BCRall115I012001 breakpoint cluster region protein (BCR) mRNA, partial cds. AY536250 - Homo sapiens isolate BCRallcl2frB012001 breakpoint cluster region protein (BCR) mRNA, partial cds. AY533677 - Homo sapiens BCR mRNA, partial cds. AY536246 - Homo sapiens isolate BCRCML2K191I072001 breakpoint cluster region protein (BCR) mRNA, partial cds. AK024483 - Homo sapiens mRNA for FLJ00077 protein, partial cds. BC169208 - Synthetic construct Homo sapiens clone IMAGE:9093269 breakpoint cluster region isoform 1 (BCR) gene, partial cds. KU234180 - Homo sapiens BCR-ABL1 fusion protein mRNA, partial cds. AB742171 - Homo sapiens mRNA for FGFR1/BCR chimera protein, partial cds. AJ298917 - Homo sapiens partial mRNA for FGFR1/BCR chimaeric fusion peptide. AB069693 - Homo sapiens mRNA for bcr/abl e8a2 fusion protein, partial cds. EU154998 - Homo sapiens BCR/ABL e8a2 fusion protein mRNA, partial cds. EU394717 - Homo sapiens BCR/ABL e8a2 fusion protein (BCR/ABL fusion) mRNA, exons 7, 8, a2 and partial cds. AY536244 - Homo sapiens isolate BCRcml2K192I072001 breakpoint cluster region protein (BCR) mRNA, partial cds. AY536249 - Homo sapiens isolate BCRcml2K23I072001 breakpoint cluster region protein (BCR) mRNA, partial cds. E00984 - Probe detection of breakpoint cluster region. M30829 - Human bcr/abl fusion protein mRNA, partial cds, clone K28. M30832 - Human bcr/abl fusion protein, partial cds, clone E3. AM491363 - Homo sapiens partial mRNA for bcr-abl1 e19a2 chimeric protein. EU236680 - Homo sapiens BCR/ABL b3a3 fusion protein (BCR/ABL fusion) mRNA, partial cds. EU394718 - Homo sapiens BCR/ABL e14a2 fusion protein (BCR/ABL fusion) mRNA, exons 12 through 14, a2, a3, a2 and partial cds. AF192533 - Homo sapiens BCR-ABL fusion protein (BCR-ABL fusion) mRNA, partial cds. AY043457 - Homo sapiens BCR-ABL fusion protein (BCR-ABL fusion) mRNA, partial cds. AF321981 - Homo sapiens BCR-ABL fusion transcript e15a2 mRNA sequence. DQ898314 - Homo sapiens isolate e13a4 BCR/ABL fusion protein (BCR/ABL fusion) mRNA, partial cds, alternatively spliced. DQ898315 - Homo sapiens isolate e14a4 BCR/ABL fusion protein (BCR/ABL fusion) mRNA, partial cds, alternatively spliced. S72478 - BCR...ABL {b3/a3 junction, translocation breakpoint} [human, Japanese CML patient 1 and ALL patient 2, peripheral blood, mononuclear cells, mRNA Mutant, 3 genes, 140 nt]. AF487522 - Homo sapiens BCRe18/ABL1e3 fusion protein (BCR/ABL fusion) mRNA, partial cds. AK122842 - Homo sapiens cDNA FLJ16453 fis, clone BRAWH3003019, highly similar to Breakpoint cluster region protein (EC 2.7.1.-). BC031568 - Homo sapiens breakpoint cluster region, mRNA (cDNA clone IMAGE:5192593), with apparent retained intron. EU394716 - Homo sapiens BCR/ABL e18-int1b-a2 fusion protein (BCR/ABL fusion) mRNA, exons, 2 and partial cds. DL490042 - Novel nucleic acids. AK124310 - Homo sapiens cDNA FLJ42318 fis, clone TRACH2021398. DQ576853 - Homo sapiens piRNA piR-44965, complete sequence. JD252663 - Sequence 233687 from Patent EP1572962. JD405642 - Sequence 386666 from Patent EP1572962. JD384569 - Sequence 365593 from Patent EP1572962. JD139025 - Sequence 120049 from Patent EP1572962. JD141908 - Sequence 122932 from Patent EP1572962. JD061380 - Sequence 42404 from Patent EP1572962. BC063619 - Homo sapiens breakpoint cluster region, mRNA (cDNA clone IMAGE:4181461). BC083493 - Homo sapiens breakpoint cluster region, mRNA (cDNA clone IMAGE:3868167), partial cds. BC041705 - Homo sapiens breakpoint cluster region, mRNA (cDNA clone IMAGE:4939126). BC127668 - Homo sapiens cDNA clone IMAGE:40128089. BC053641 - Homo sapiens breakpoint cluster region, mRNA (cDNA clone IMAGE:4500154). JD498487 - Sequence 479511 from Patent EP1572962. JD462977 - Sequence 444001 from Patent EP1572962. JD199865 - Sequence 180889 from Patent EP1572962. JD475980 - Sequence 457004 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa05200 - Pathways in cancer hsa05220 - Chronic myeloid leukemia
BioCarta from NCI Cancer Genome Anatomy Project h_gleevecpathway - Inhibition of Cellular Proliferation by Gleevec h_integrinPathway - Integrin Signaling Pathway
Reactome (by CSHL, EBI, and GO)
Protein P11274 (Reactome details) participates in the following event(s):
R-HSA-1839031 Dimerization of cytosolic FGFR1 fusion proteins R-HSA-1839067 Phosphorylation of BCR moiety of BCR-FGFR1 R-HSA-1839095 p-BCR-pFGFR1 binds GRB2:GAB2 R-HSA-194922 GAPs inactivate Rho GTPase:GTP by hydrolysis R-HSA-1839039 Tyrosine kinase inhibitors bind and inhibit cytosolic FGFR1 fusion dimer phosphorylation R-HSA-1839065 Phosphorylation of cytosolic FGFR1 fusion dimers R-HSA-1839110 p-BCR-p-FGFR1 phosphorylates GAB2 R-HSA-1839114 BCR-FGFR1:GRB2:p-GAB2 binds PIK3R1 R-HSA-1839080 Activated cytosolic FGFR1 fusions bind PIK3CA R-HSA-1839112 Phosphorylation of STAT5 by cytosolic FGFR1 fusions R-HSA-1839102 BCR-FGFR1 fusion:GRB2:p-GAB2:PIK3R1 binds PIK3CA R-HSA-1839094 Activated FGFR1 mutants and fusions bind PLCG1 R-HSA-1839100 p-4Y- PLCG1 dissociates from activated FGFR1 mutants and fusions R-HSA-1839098 Activated FGFR1 mutants and fusions phosphorylate PLCG1 R-HSA-1839091 Cytosolic FGFR1 fusion protein-associated PI3K phosphorylates PIP2 to PIP3 R-HSA-1839107 BCR-FGFR1-associated PI3K phosphorylates PIP2 to PIP3. R-HSA-1839117 Signaling by cytosolic FGFR1 fusion mutants R-HSA-194840 Rho GTPase cycle R-HSA-1839124 FGFR1 mutant receptor activation R-HSA-194315 Signaling by Rho GTPases R-HSA-5655302 Signaling by FGFR1 in disease R-HSA-162582 Signal Transduction R-HSA-1226099 Signaling by FGFR in disease R-HSA-5663202 Diseases of signal transduction R-HSA-1643685 Disease