| 简介 | 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]
Diseases associated with BCR include Leukemia, Chronic Myeloid and B-Lymphoblastic Leukemia/Lymphoma With T(9;22)(Q34.1;Q11.2). Among its related pathways are Ponatinib Pathway, Pharmacokinetics/Pharmacodynamics and RHOC GTPase cycle. Gene Ontology (GO) annotations related to this gene include protein tyrosine kinase activity and enzyme binding. An important paralog of this gene is ABR.
Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins.
The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42.
Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:17116687, 1903516, 7479768).
The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1.
Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:23940119, 7479768).
The amino terminus contains an intrinsic kinase activity (PubMed:1657398).
Functions as an important negative regulator of neuronal RAC1 activity (By similarity).
Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687).
Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (PubMed:23940119).
breakpoint cluster region
Postsynaptic density {ECO:0000250 UniProtKB:Q6PAJ1}
Cell projection, dendritic spine {ECO:0000250 UniProtKB:Q6PAJ1}
Cell projection, axon {ECO:0000250 UniProtKB:Q6PAJ1}
Synapse {ECO:0000250 UniProtKB:F1LXF1}
cytosol 5
extracellular 5
Quaternary structure:
Homotetramer.
Interacts with PDZK1 (PubMed:15494376).
May interact with CCPG1 (By similarity).
Interacts with FES/FPS, ABL1, PIK3R1 and GRB2 (PubMed:15302586, 1712671, 9407116).
Interacts with HCK (PubMed:9407116).
Interacts with SH2D5 (PubMed:25331951).
Interacts with DLG4 (PubMed:20962234). |
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