Scientific Background: BCR (also known as breakpoint cluster region) encodes a phosphoprotein that has serine/threonine kinase activity (1). The human c-ABL oncogene is translocated from chromosome 9 to a region on chromosome 22 (associated with BCR) in chronic myelocytic leukemia. In classical t(9;22) translocation, as observed in chronic granulocytic leukemia (CGL), a hybrid DNA unit is produced comprising the BCR gene product plus the translocated c-ABL gene from chromosome 9. The BCR-ABL hybrid protein (p210) is formed that displays increased tyrosine kinase activity. A similar DNA rearrangement of the p210 protein is also found in cases of Philadelphia-positive acute lymphoblastic leukemia (ALL) (2).
2. Eridani, S. et al: Molecular biology of Philadelphia chromosome in chronic granulocytic leukaemia and acute lymphoblastic leukaemia. Cytotechnology; 1: 33-36.
NCBI and Uniprot Product Information
NCBI Description
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]
Uniprot Description
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.
Research Articles on BCR
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Product Notes
The BCR bcr (Catalog #AAA515124) is a Recombinant Protein produced from Sf9 insect cells and is intended for research purposes only. The product is available for immediate purchase. The immunogen sequence is 1-695 with tag GST tag!!Expression System||Sf9 insect cells using baculovirus!!Source Note||Recombinant human BCR (1-695) was expressed by baculovirus in Sf9 insect cells. AAA Biotech's BCR can be used in a range of immunoassay formats including, but not limited to, Western Blot (WB). Researchers should empirically determine the suitability of the BCR bcr for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "BCR, Recombinant Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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