BCR, Recombinant Protein

ALL; CML; PHL; BCR1; D22S11; D22S662; FLJ1645

For Research Use Only. Not for use in diagnostic procedures.

Chromosome: 22; NC_000022.10 (23522402..23660224). Location: 22q11.23

Sf9 insect cells

50mM Tris-HCl, pH 7.5, 150mM NaCl, 10mM glutathione, 0.1mM EDTA, 0.25mM DTT, 0.1mM PMSF, 25% glycerol.

Store product at -70 degree C. For optimal storage, aliquot target into smaller quantities after centrifugation and store at recommended temperature. For most favorable performance, avoid repeated handling and multiple freeze/thaw cycles.

Small volumes of BCR recombinant protein vial(s) may occasionally become entrapped in the seal of the product vial during shipment and storage. If necessary, briefly centrifuge the vial on a tabletop centrifuge to dislodge any liquid in the container`s cap. Certain products may require to ship with dry ice and additional dry ice fee may apply.

Recombinant human BCR (1-695) was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag.

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).

Cellular Proteins; Signaling Proteins - Cellular Proteins

Western Blot (WB)

~120 kDa

breakpoint cluster region

breakpoint cluster region protein; BCR/FGFR1 chimera protein; FGFR1/BCR chimera protein; renal carcinoma antigen NY-REN-26

Breakpoint cluster region protein

BCR1; D22S11  [Similar Products]

BCR_HUMAN

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.

1. Stam, K. et al: Evidence that the phl gene encodes a 160,000-dalton phosphoprotein with associated kinase activity. Mol. Cell Biol. 1987; 7(5): 1955-1960.
2. Eridani, S. et al: Molecular biology of Philadelphia chromosome in chronic granulocytic leukaemia and acute lymphoblastic leukaemia. Cytotechnology; 1: 33-36.

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