a protein with serine/threonine protein kinase activity and is a GTPase-activating protein (GAP) for RAC1 and CDC42. The amino-terminal region of Bcr contains an oligomerization domain, a serine/threonine kinase domain and a region that binds SH2 domains. The middle of the protein has a PH domain and a region of sequence similarity to the guanine nucleotide exchange factors for the Rho family of GTP binding proteins. The carboxy-terminal region promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. A breakpoint cluster region protein that participates in a t(9;22)(q34;q11) chromosomal translocation that produces a BCR-ABL oncogene responsible for chronic myeloid leukemia (CML), acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The function of wild type Bcr in cells remains unclear. PDGF receptor may use Bcr as a downstream signaling mediator. Tyr177 of human Bcr, phosphorylated in the Bcr-Abl fusion protein, provides a docking site for Gab2 and GRB2, and is important in the transforming activity of Bcr-Abl. Sequence variants of the Bcr protein may be associated with bipolar disorder. Two alternatively spliced isoforms of the human protein have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 126.96.36.199; Kinase, protein; GAPs, Rac/Rho; Protein kinase, atypical; Protein kinase, Ser/Thr (non-receptor); GAPs; ATYPICAL group; BCR family
Cellular Component: protein complex; plasma membrane; cytosol
Molecular Function: protein serine/threonine kinase activity; protein binding; Rho guanyl-nucleotide exchange factor activity; enzyme binding; Rac GTPase activator activity; protein-tyrosine kinase activity; kinase activity; ATP binding; GTPase activator activity
Biological Process: inner ear morphogenesis; peptidyl-tyrosine phosphorylation; regulation of cell cycle; protein amino acid autophosphorylation; platelet-derived growth factor receptor signaling pathway; response to lipopolysaccharide; signal transduction; protein amino acid phosphorylation; regulation of small GTPase mediated signal transduction; negative regulation of neutrophil degranulation; negative regulation of inflammatory response; small GTPase mediated signal transduction; positive regulation of phagocytosis; brain development; actin cytoskeleton organization and biogenesis; neuromuscular process controlling balance; negative regulation of cell migration
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.