The breakpoint cluster region protein (BCR) also known as renal carcinoma antigen NY-REN-26 is a protein that in humans is encoded by the BCR gene. BCR is one of the two genes in the BCR-ABL complex, which is associated with the Philadelphia chromosome. Two transcript variants encoding different isoforms have been found for this gene.
BCR |
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Available structures |
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PDB | Ortholog search: PDBe RCSB |
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List of PDB id codes |
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1K1F, 2AIN |
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Identifiers |
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Aliases | BCR, Bcr, 5133400C09Rik, AI561783, AI853148, mKIAA3017, ALL, BCR1, CML, D22S11, D22S662, PHL, RhoGEF and GTPase activating protein, BCR gene, BCR activator of RhoGEF and GTPase |
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External IDs | OMIM: 151410 MGI: 88141 HomoloGene: 3192 GeneCards: BCR |
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Gene location (Human) |
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| Chr. | Chromosome 22 (human)[1] |
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| Band | 22q11.23 | Start | 23,179,704 bp[1] |
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End | 23,318,037 bp[1] |
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Gene location (Mouse) |
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| Chr. | Chromosome 10 (mouse)[2] |
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| Band | 10 C1|10 38.49 cM | Start | 75,060,592 bp[2] |
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End | 75,184,921 bp[2] |
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Gene ontology |
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Molecular function | • transferase activity • nucleotide binding • guanyl-nucleotide exchange factor activity • kinase activity • protein serine/threonine kinase activity • GO:0001948 protein binding • enzyme binding • protein tyrosine kinase activity • ATP binding • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity
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Cellular component | • cytoplasm • cytosol • postsynaptic membrane • membrane • GO:0097483, GO:0097481 postsynaptic density • cell membrane • synapse • cell junction • extracellular exosome • protein-containing complex • Schaffer collateral - CA1 synapse • glutamatergic synapse • postsynaptic density, intracellular component • intracellular anatomical structure
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Biological process | • positive regulation of phagocytosis • GO:0007243 intracellular signal transduction • neuromuscular process controlling balance • phosphorylation • regulation of cell cycle • negative regulation of blood vessel remodeling • protein phosphorylation • negative regulation of cellular extravasation • response to lipopolysaccharide • brain development • regulation of vascular permeability • negative regulation of cell migration • negative regulation of neutrophil degranulation • inner ear morphogenesis • protein autophosphorylation • platelet-derived growth factor receptor signaling pathway • regulation of Rho protein signal transduction • regulation of small GTPase mediated signal transduction • negative regulation of inflammatory response • actin cytoskeleton organization • signal transduction • peptidyl-tyrosine phosphorylation • renal system process • homeostasis of number of cells • regulation of nitrogen compound metabolic process • definitive hemopoiesis • negative regulation of respiratory burst • intracellular protein transmembrane transport • cellular response to lipopolysaccharide • negative regulation of reactive oxygen species metabolic process • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • modulation of chemical synaptic transmission • small GTPase mediated signal transduction • keratinocyte differentiation • focal adhesion assembly • GO:0032861, GO:0032862, GO:0032856 activation of GTPase activity
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Sources:Amigo / QuickGO |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | | |
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RefSeq (protein) | | |
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Location (UCSC) | Chr 22: 23.18 – 23.32 Mb | Chr 10: 75.06 – 75.18 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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structure of the bcr-abl oncoprotein oligomerization domain |
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Bcr-Abl_Oligo |
PF09036 |
IPR015123 |
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structures / ECOD | RCSB PDB; PDBe; PDBj | structure summary |
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Although the BCR-ABL fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The protein has serine/threonine kinase activity and is a guanine nucleotide exchange factor for Rho family GTPases including RhoA.[5][6]
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 that is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint.[7]
Schematic of the BCR-ABL formation through chromosomal translocation
The BCR-ABL oncoprotein oligomerisation domain found at the N-terminus of BCR is essential for the oncogenicity of the BCR-ABL fusion protein. The BCR-ABL oncoprotein oligomerisation domain consists of a short N-terminal helix (alpha-1), a flexible loop and a long C-terminal helix (alpha-2). Together these form an N-shaped structure, with the loop allowing the two helices to assume a parallel orientation. The monomeric domains associate into a dimer through the formation of an antiparallel coiled coil between the alpha-2 helices and domain swapping of two alpha-1 helices, where one alpha-1 helix swings back and packs against the alpha-2 helix from the second monomer. Two dimers then associate into a tetramer.[8]
The BCR protein has been shown to interact with:
- Abl gene,[9][10][11]
- CD117,[12]
- CRKL[13][14][15][16]
- FES,[17][18]
- Grb2,[9][13][14][18][19][20]
- GRB10,[13]
- HCK,[21][22]
- MLLT4,[23]
- PXN,[24][25]
- PIK3CG,[13][24][26]
- PTPN6,[27]
- PTPRT(PTPrho)[28]
- SOS1,[9][18] and
- XPB.[29]
- BCR+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- Human BCR genome location and BCR gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: P11274 (Human Breakpoint cluster region protein) at the PDBe-KB.
This article incorporates text from the public domain Pfam and InterPro: IPR015123