Genomic structure and promoter sequence of the insulin-dependent diabetes mellitus autoantigen, IA-2 (PTPRN)

Genomics. 1998 Dec 1;54(2):338-43. doi: 10.1006/geno.1998.5583.


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.

MeSH terms

  • Autoantibodies / genetics*
  • Autoantibodies / immunology
  • Autoantigens
  • Base Sequence
  • Cloning, Molecular
  • Diabetes Mellitus, Type 1 / genetics*
  • Exons / genetics
  • Genes, Reporter / genetics
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / immunology
  • Humans
  • Introns / genetics
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / genetics*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Restriction Mapping
  • Sequence Analysis, DNA
  • Sequence Deletion / genetics
  • Transfection / genetics
  • Tumor Cells, Cultured


  • Autoantibodies
  • Autoantigens
  • ICA512 autoantibody
  • Membrane Proteins
  • PTPRN protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Glutamate Decarboxylase

Associated data

  • GENBANK/AF042285