Parker, N; Porter, ACG; (2004) Identification of a novel gene family that includes the interferon-inducible human genes 6-16 and ISG12. BMC GENOMICS , 5 , Article 8. 10.1186/1471-2164-5-8.

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Abstract

Background: The human 6 - 16 and ISG12 genes are transcriptionally upregulated in a variety of cell types in response to type I interferon (IFN). The predicted products of these genes are small (12.9 and 11.5 kDa respectively), hydrophobic proteins that share 36% overall amino acid identity. Gene disruption and over-expression studies have so far failed to reveal any biochemical or cellular roles for these proteins.Results: We have used in silico analyses to identify a novel family of genes ( the ISG12 gene family) related to both the human 6 - 16 and ISG12 genes. Each ISG12 family member codes for a small hydrophobic protein containing a conserved similar to80 amino-acid motif ( the ISG12 motif). So far we have detected 46 family members in 25 organisms, ranging from unicellular eukaryotes to humans. Humans have four ISG12 genes: the 6 - 16 gene at chromosome 1p35 and three genes ( ISG12( a), ISG12(b) and ISG12( c)) clustered at chromosome 14q32. Mice have three family members ( ISG12( a), ISG12(b1) and ISG12(b2)) clustered at chromosome 12F1 (syntenic with human chromosome 14q32). There does not appear to be a murine 6 - 16 gene. On the basis of phylogenetic analyses, genomic organisation and intron-alignments we suggest that this family has arisen through divergent inter- and intra-chromosomal gene duplication events. The transcripts from human and mouse genes are detectable, all but two ( human ISG12( b) and ISG12( c)) being upregulated in response to type I IFN in the cell lines tested.Conclusions: Members of the eukaryotic ISG12 gene family encode a small hydrophobic protein with at least one copy of a newly defined motif of similar to80 amino-acids ( the ISG12 motif). In higher eukaryotes, many of the genes have acquired a responsiveness to type I IFN during evolution suggesting that a role in resisting cellular or environmental stress may be a unifying property of all family members. Analysis of gene-function in higher eukaryotes is complicated by the possibility of functional redundancy between family-members. Genetic studies in organisms ( e. g. Dictyostelium discoideum) with just one family member so far identified may be particularly helpful in this respect.

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