BCR (gene)

The breakpoint cluster region protein (BCR) also known as renal carcinoma antigen NY-REN-26 is a is_associated_with::protein that in humans is encoded by the BCR is_associated_with::gene. BCR is one of the two genes in the BCR-ABL complex, which is associated with the is_associated_with::Philadelphia chromosome. Two transcript variants encoding different isoforms have been found for this gene.

Function
Although the BCR-ABL is_associated_with::fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The protein has is_associated_with::serine/threonine kinase activity and is a is_associated_with::GTPase-activating protein for is_associated_with::RAC1 and is_associated_with::CDC42.

Clinical significance
A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with is_associated_with::chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the BCR gene. The translocation produces a fusion protein that is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint.

Structure
The Bcr-Abl oncoprotein oligomerisation domain found at the is_associated_with::N-terminus of BCR is essential for the is_associated_with::oncogenicity of the BCR-ABL fusion protein. The Bcr-Abl oncoprotein oligomerisation domain consists of a short N-terminal is_associated_with::helix (alpha-1), a flexible loop and a long C-terminal helix (alpha-2). Together these form an N-shaped structure, with the loop allowing the two helices to assume a parallel orientation. The monomeric domains associate into a dimer through the formation of an antiparallel is_associated_with::coiled coil between the alpha-2 helices and domain swapping of two alpha-1 helices, where one alpha-1 helix swings back and packs against the alpha-2 helix from the second is_associated_with::monomer. Two dimers then associate into a is_associated_with::tetramer.

Interactions
BCR gene has been shown to interact with:


 * is_associated_with::Abl gene,
 * is_associated_with::CD117,
 * is_associated_with::CRKL
 * FES,
 * is_associated_with::Grb2,
 * is_associated_with::GRB10,
 * is_associated_with::HCK,
 * is_associated_with::MLLT4,
 * PXN,
 * is_associated_with::PIK3CG,
 * is_associated_with::PTPN6,
 * is_associated_with::PTPRT(PTPrho)
 * is_associated_with::SOS1, and
 * is_associated_with::XPB.