BCR 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]

Function: GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. Displays serine/threonine kinase activity. Ref.13 Ref.15

Catalytic activity: ATP + a protein = ADP + a phosphoprotein.

Subunit structure: Homotetramer. Interacts with PDZK1. May interact with CCPG1

By similarity. Interacts with FES/FPS, ABL1, PIK3R1 and GRB2. Interacts with HCK. Ref.14 Ref.16 Ref.19 Ref.20 Ref.27

Domain: The region involved in binding to ABL1 SH2-domain is rich in serine residues and needs to be Ser/Thr phosphorylated prior to SH2 binding. This region is essential for the activation of the ABL1 tyrosine kinase and transforming potential of the chimeric BCR-ABL oncogene. Ref.14The DH domain is involved in interaction with CCPG1

By similarity. Ref.14

Post-translational modification: 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. Ref.16 Ref.19

Involvement in disease: Leukemia, chronic myeloid (CML) [MIM:608232]: 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.Note: The gene represented in this entry is involved in disease pathogenesis.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).

Sequence similarities: Contains 1 C2 domain.Contains 1 DH (DBL-homology) domain.Contains 1 PH domain.Contains 1 Rho-GAP domain.

Sequence caution: The sequence BAE06073.1 differs from that shown. Reason: Erroneous initiation.