Molecular cloning, physical mapping, and expression analysis of a novel gene, BCL2L12, encoding a proline-rich protein with a highly conserved BH2 domain of the Bcl-2 family

Members of the Bcl-2 family of apoptosis-regulating proteins contain at lea st one of the four evolutionarily conserved domains, termed BH1, BH2, BH3, or BH4, Here, we report the identification, cloning, physical mapping, and expression pattern of BCL2L12, a novel gene that encodes a BCL2-like prolin e-rich protein. Proline-rich sites have been shown to interact with Src hom ology region 3 (SH3) domains of several tyrosine kinases, mediating their o ncogenic potential. This new gene maps to chromosome 19q13.3 and is located between the IRF3 and the PRMT1/HRMT1L2 genes, close to the RRAS gene. BCL2 L12 is composed of seven coding exons and six intervening introns, spanning a genomic area of 8.8 kb, All of the exon-intron splice sites conform to t he consensus sequence for eukaryotic splice sites. The BCL2L12 protein is c omposed of 334 amino acids, with a calculated molecular mass of 36.8 kDa an d an isoelectric point of 9.45, The BCL2L12 protein contains one BH2 homolo gy domain, one proline-rich region similar to the TC21 protein and, five co nsensus PXXP tetrapeptide sequences. BCL2L12 is expressed mainly in breast, thymus, prostate, fetal liver, colon, placenta, pancreas, small intestine, spinal cord, kidney, and bone marrow and to a lesser extent in many other tissues. We also identified one splice variant of BCL2L12 that is primarily expressed in skeletal muscle. (C) 2001 Academic Press.