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Limited but significant sequence similarity has been observed between an uncharacterized human protein, SIN1, and the S. pombe SIN1, Dictyostelium RIP3 and S. cerevisiae AVO1 proteins. The human Sin1 gene has been automatically predicted (MAPKAP1; GenBank accession number NM_024117); however, this sequence appears to be incomplete. In this study, we have cloned and characterized the full-length human Sin1 mRNA and identified a highly conserved domain that defines the family of SIN1 orthologues, members of which are widely distributed in the fungal and metazoan kingdoms. We demonstrate that Sin1 transcripts can use alternative polyadenylation signals and describe a number of Sin1 splice variants that potentially encode functionally different isoforms. (C) 2004 Elsevier B.V. All rights reserved.