Genomic Structure and Promoter Sequence of the Insulin-Dependent Diabetes Mellitus Autoantigen, IA-2 (PTPRN)

IA-2 is a transmembrane protein tyrosine phosphatase, expressed in neuroendocrine cells, and a major autoantigen in insulin-dependent diabetes mellitus. In the present study we elucidated the structure of the IA-2 gene (HGMW-approved symbol PTPRN) and its promoter sequence. A 40-kb genomic clone covering the whole IA-2 coding sequence and 4 kb proximal 5′-upstream sequence was isolated and mapped. The IA-2 gene encompasses approximately 20 kb with 23 exons ranging from 34 bp to more than 650 bp. The extracellular domain is encoded by exons 1–12, the transmembrane region by exon 13, and the intracellular domain by exons 14–23. The transcriptional start site(s) of the IA-2 gene was mapped by 5′ rapid amplification of cDNA ends to 97 bp upstream of the translational start site. A 3-kb 5′-upstream region was sequenced, revealing a GC-rich region and TATA-less sequence containing several potential transcription-regulating sites (i.e., Sp1, CREB, GATA-1, and MZF). Functional promoter activity was confirmed by transient transfection of U87MG cells with deletion mutants linked to a luciferase reporter gene.