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 neuroend ocrine cells, and a major autoantigen in insulin-dependent diabetes mellitu s. 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 cov ering 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 wit h 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 int racellular 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 upstre am of the translational start site. A 3-kb 5'-upstream region was sequenced , revealing a GC-rich region and TATA-less sequence containing several pote ntial transcription-regulating sites (i.e., Spl, CREB, GATA-1, and MZF). Fu nctional promoter activity was confirmed by transient transfection of U87MG cells with deletion mutants linked to a luciferase reporter gene. (C) 1998 Academic Press.