An aminophospholipid translocase associated with body fat and type 2 diabetes phenotypes

We have shown that a region on proximal mouse chromosome 7, near the pink-eyed (p) dilution locus, contains an ATPase (pfatp), a putative aminophospholipid translocase. Studies have suggested that this gene is a prime candidate for modulating body fat or involved in lipid metabolism in mouse and humans. Toward further analyses, our objective was to generate the complete genomic structures of mouse and human genes.

The genomic structure of mouse pfatp was deduced by comparing the full-length cDNA sequence with the genomic sequence derived from a mouse BAC. The human ortholog was identified from the National Center for Biotechnology Information database. Full-length cDNA was generated, and the corresponding genomic structure was deduced from the Human Genome Database.

Murine pfatp, and its human ortholog, PFATP, belong to class V of the third subfamily of P-type ATPases. The gene organization is strikingly similar in both organisms and all exon-intron junctions are conserved. A putative promoter region of PFATP contains a strong CpG island. The 5' untranslated regions of the two cDNAs have potential binding sites for multiple transcription factors, including Sp1, USF, AP1, and AP2, involved in adipogenesis and adipocyte metabolism.

We report the generation of the complete genomic structure of a novel aminophospholipid translocase in mice and humans. Because the exact biological role and the subsequent relevance of these ATPases to obesity and diabetes are unknown, these data help to delineate the role of these genes in lipid/adipocyte metabolism.