BCR-RET Recombinant Protein

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]

Bcr: 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.

Protein type: ATYPICAL group; BCR family; EC 2.7.11.1; GAP; GAP, Rac/Rho; GEF, Rac/Rho; Kinase, protein; Oncoprotein; Protein kinase, Ser/Thr (non-receptor); Protein kinase, atypical

Chromosomal Location of Human Ortholog: 22q11.23

Cellular Component: cytosol; membrane; postsynaptic density; protein complex

Molecular Function: GTPase activator activity; kinase activity; protein binding; protein-tyrosine kinase activity

Biological Process: positive regulation of GTPase activity; protein amino acid phosphorylation; regulation of small GTPase mediated signal transduction; signal transduction

Disease: Leukemia, Acute Lymphoblastic; Leukemia, Chronic Myeloid