BCR (gene)

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 fusion protein, which is associated with the Philadelphia chromosome. Two transcript variants encoding different isoforms have been found for this gene.

BCR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1K1F, 2AIN
Identifiers
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
External IDs	OMIM: 151410; MGI: 88141; HomoloGene: 3192; GeneCards: BCR; OMA:BCR - orthologs
Gene location (Human) Chr. Chromosome 22 (human)[1] Band 22q11.23 Start 23,179,704 bp[1] End 23,318,037 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 C1|10 38.49 cM Start 74,896,424 bp[2] End 75,020,753 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in nucleus accumbens caudate nucleus putamen anterior pituitary olfactory zone of nasal mucosa sural nerve right frontal lobe prefrontal cortex amygdala right lobe of thyroid gland Top expressed in olfactory tubercle nucleus accumbens superior frontal gyrus globus pallidus visual cortex primary visual cortex dentate gyrus of hippocampal formation granule cell ventromedial nucleus neural layer of retina anterior amygdaloid area More reference expression data BioGPS n/a
Gene ontology Molecular function transferase activity nucleotide binding guanyl-nucleotide exchange factor activity kinase activity protein serine/threonine kinase activity protein binding enzyme binding protein tyrosine kinase activity ATP binding GTPase activator activity Cellular component cytoplasm cytosol postsynaptic membrane membrane postsynaptic density plasma membrane synapse cell junction extracellular exosome protein-containing complex Schaffer collateral - CA1 synapse glutamatergic synapse postsynaptic density, intracellular component intracellular anatomical structure Biological process positive regulation of phagocytosis 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 positive regulation of GTPase activity modulation of chemical synaptic transmission small GTPase mediated signal transduction keratinocyte differentiation focal adhesion assembly activation of GTPase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 613 110279 Ensembl ENSG00000186716 ENSMUSG00000009681 UniProt P11274 Q6PAJ1 RefSeq (mRNA) NM_004327 NM_021574 NM_001081412 RefSeq (protein) NP_004318 NP_067585 NP_001074881 Location (UCSC) Chr 22: 23.18 – 23.32 Mb Chr 10: 74.9 – 75.02 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Bcr-Abl oncoprotein oligomerisation domain
structure of the bcr-abl oncoprotein oligomerization domain
Identifiers
Symbol	Bcr-Abl_Oligo
Pfam	PF09036
InterPro	IPR015123
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Structure

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.^[5] Structure-based engineering starting from the antiparallel coiled coil domain of the BCR-ABL oncoprotein (BCR30-65) resulted in a new pH-sensitive homodimeric antiparallel coiled coil.^[6]

Function

Although the BCR-ABL fusion protein has been much studied, the function of the normal BCR gene product is still not clear. The protein has serine/threonine kinase activity and is a guanine nucleotide exchange factor for the Rho family of GTPases including RhoA.^[7][8]

Interactions

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]

Clinical significance

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.^[30]

See also

• Abl gene