During comprehensive sequence analysis of human chromosome 22, we identified a novel gene family consisting of five members (YPEL1 through YPEL5) which has high homology with Drosophila yippee gene. We cloned and sequenced cDNAs for all five genes and determined their exon/intron organization. These YPEL genes showed high homology (43.8-96.6%) at amino acid sequence level among them. Mouse counterparts (Ypel1 through Ypel5) were also identified in the syntenic region of mouse chromosomes and their cDNAs were cloned and sequenced. Each of five pairs of human/mouse orthologs revealed extremely high homology. Thus, we named these genes as members of YPEL gene family. We searched YPEL family genes from the public databases, and found 100 genes from 68 species including animals, plants and fungi. Amino acid sequences of these 100 YPEL proteins were extremely similar and a consensus sequence of C-X-2-C-X-19-G-X-3-L-X-5-N-X-13-G-X-8-C-X-2-C-X-4-GWXY-X-10-K-X-6-E was established for all the YPEL family proteins without exception. Interestingly, the indirect immunofluorescent staining indicated that YPEL 1-4 proteins are localized to the centrosome and nucleolus during interphase and at several dot-like structures around the mitotic apparatus during mitotic phase of COS-7 cells. YPEL5 protein is localized to the centrosome and nucleus during interphase and at the mitotic spindle during mitosis of the same cell line. Thus, the YPEL family proteins were found in essentially all the eukaryotes and hence they must play important roles in the maintenance of life. The subcellular localization of YPEL proteins in association with centrosome or mitotic spindle suggests a novel function involved in the cell division. (C) 2004 Elsevier B.V. All rights reserved.