A new gene family including DSCR1 (Down syndrome candidate region 1) and ZAKI-4: Characterization from yeast to human and identification of DSCR1-like 2, a novel human member (DSCR1L2)

A new gene family has been identified on the basis of in-depth bioinformati cs analysis of the Down syndrome candidate region 1 (DSCR1) gene, located o n 21q22.1. We have determined the complete coding sequences of similar gene s in Saccharomyces cerevisiae and Caenorhabditis elegans, as well as that o f a novel human gene, named DSCR1L2 (DSC1R2-like 2). Peripheral blood leuko cyte cDNA sequencing predicts as its product a 241-amino-acid protein highl y similar to products of the human genes DSCR1 and ZAKI-4 (HGMW-approved sy mbol DSCR1L1). The highest level of expression of DSCR1L2 mRNA was found by Northern blot analysis in heart and skeletal muscles, liver, kidney, and p eripheral blood leukocytes (three transcripts of 3.2, 5.2, and 7.5 kb). The gene consists of four exons and spans about 22 kb on chromosome 1 (1p33-p3 5.3) (Human Chromosome 1, Sanger Centre). Exon/ intron organization is high ly conserved between DSCR1 and DSCR1L2. Two alternative DSCR1L2 mRNA splici ng forms have been recognized, with one lacking 10 amino acids in the middl e of the protein. Analysis of expressed sequence tags (ESTs) shows DSCR1L2 expression in fetal tissues (heart, liver, and spleen) and in adenocarcinom as. ESTs related to the murine DSCR1L2 orthologue are found in the 2-cell s tage mouse embryo, in developing brain stem and spinal cord, and in thymus and T cells. The most prominent feature identified in the protein family is a central short, unique serine-proline motif (including an ISPPXSPP box), which is strongly conserved from yeast to human but is absent in bacteria. Moreover, homology with the RNA-binding domain was weakly but consistently detected in a stretch of 80 amino acids at the amino-terminus by fine seque nce analysis based on tools utilizing both hidden Markov models and BLAST. The identification of this new gene family should allow a better understand ing, of the functions of the genes belonging to it. (C) 2000 Academic Press .