BCR (gene)
The breakpoint cluster region protein (BCR) also known as renal carcinoma antigen NY-REN-26 is a protein that in humans is encoded by the "BCR" gene. "BCR" is one of the two genes in the "BCR-ABL" fusion protein, which is associated with the Philadelphia chromosome. Two transcript variants encoding different isoforms have been found for this gene. Function. Although the BCR-ABL fusion protein has been studied endless times, the function of the normal BCR gene product is still not clear. The protein has serine/threonine kinase activity and is a guanine nucleotide exchange factor for Rho  family GTPases including RhoA. Clinical significance. 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 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 N-terminus of BCR is essential for the oncogenicity of the BCR-ABL fusion protein. The BCR-ABL oncoprotein oligomerisation domain consists of a short N -terminal 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 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 monomer. Two dimers then associate into a tetramer. Structure-based engineering starting from the antiparallel coiled coil domain of the BCR-ABL oncoprotein (BCR) resulted in a  new pH-sensitive homodimeric antiparallel coiled coil. Interactions. The BCR protein has been shown to interact with: See also. Abl is also connected to Bcr they are a gene, shaped together.