Bcr

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 protein has serine/threonine kinase activity and is a GTPase-activating protein for p21rac. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Full Name

BCR, RhoGEF And GTPase Activating Protein

Function

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:7479768, PubMed:1903516, PubMed:17116687).
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:7479768, PubMed:23940119).
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).

Biological Process

Activation of GTPase activity Source: UniProtKB
Focal adhesion assembly Source: UniProtKB
Keratinocyte differentiation Source: UniProtKB
Modulation of chemical synaptic transmission Source: UniProtKB
Platelet-derived growth factor receptor signaling pathway Source: Ensembl
Protein autophosphorylation Source: Ensembl
Protein phosphorylation Source: ProtInc
Regulation of Rho protein signal transduction Source: UniProtKB
Regulation of small GTPase mediated signal transduction Source: Reactome
Signal transduction Source: ProtInc
Small GTPase mediated signal transduction Source: UniProtKB

Cellular Location

Postsynaptic density; Dendritic spine; Axon; Synapse

Involvement in disease

Leukemia, chronic myeloid (CML): A 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.
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).

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.