title: 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).
abstract: A new gene family has been identified on the basis of in-depth bioinformatics analysis of the Down syndrome candidate region 1 (DSCR1) gene, located on 21q22.1. We have determined the complete coding sequences of similar genes in Saccharomyces cerevisiae and Caenorhabditis elegans, as well as that of a novel human gene, named DSCR1L2 (DSCR1-like 2). Peripheral blood leukocyte cDNA sequencing predicts as its product a 241-amino-acid protein highly similar to products of the human genes DSCR1 and ZAKI-4 (HGMW-approved symbol DSCR1L1). The highest level of expression of DSCR1L2 mRNA was found by Northern blot analysis in heart and skeletal muscles, liver, kidney, and peripheral 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-p35.3) (Human Chromosome 1, Sanger Centre). Exon/intron organization is highly conserved between DSCR1 and DSCR1L2. Two alternative DSCR1L2 mRNA splicing forms have been recognized, with one lacking 10 amino acids in the middle of the protein. Analysis of expressed sequence tags (ESTs) shows DSCR1L2 expression in fetal tissues (heart, liver, and spleen) and in adenocarcinomas. ESTs related to the murine DSCR1L2 orthologue are found in the 2-cell stage 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 sequence analysis based on tools utilizing both hidden Markov models and BLAST. The identification of this new gene family should allow a better understanding of the functions of the genes belonging to it.
authors.affiliation: Istituto di Istologia ed Embriologia Generale, Università di Bologna, Bologna, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Strippoli
authors.forename: L
authors.initials: L
authors.lastname: Lenzi
authors.forename: M
authors.initials: M
authors.lastname: Petrini
authors.forename: P
authors.initials: P
authors.lastname: Carinci
authors.forename: M
authors.initials: M
authors.lastname: Zannotti
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D004314:Down Syndrome / Q000235:genetics*; D005091:Exons; D020224:Expressed Sequence Tags; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C486303:Dscr1l1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D011506:Proteins; C108612:RCAN1 protein, human; C100360:RCAN2 protein, human; C408372:RCAN3 protein, human; C473752:RCN-1 protein, C elegans; C486302:RCN1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins