Alternative titles; symbols
HGNC Approved Gene Symbol: PTPRN2
Cytogenetic location: 7q36.3 Genomic coordinates (GRCh38): 7:157,539,056-158,587,823 (from NCBI)
Cui et al. (1996) used degenerate PCR to screen for protein-tyrosine phosphatases (PTPases) in a human colon carcinoma cell cDNA library and isolated the PTPRN2 gene, which termed IAR (for islet antigen-related). The predicted protein of 1,015 amino acids is 43% identical to IA2 (PTPRN; 601773), an autoantigen associated with insulin-dependent diabetes mellitus (IDDM; 222100). They found that the intracellular domains of IAR and IA2 are 73% identical. Northern blot analysis showed that IAR was expressed as 5.5- and 3.7-kb transcripts primarily in human brain and pancreas. Cui et al. (1996) noted that the IAR extracellular region contains the adhesion recognition peptide sequence RDGS. The authors demonstrated that IAR has phosphatase activity. They found that IAR is reactive with sera from patients with IDDM and that IAR and IA2 identify overlapping but nonidentical sets of IDDM patients. Morahan et al. (1998) noted that autoantibodies to IAR are significantly more predictive of disease than those to IA2.
Kawasaki et al. (1996) cloned and characterized a human cDNA for the PTPRN2 gene, which they called phogrin. Wasmeier and Hutton (1996) originally identified phogrin, named for 'phosphatase homolog in granules of insulinoma,' by expression screening of a rat insulinoma cDNA library. The human phogrin gene, with a predicted molecular mass of 111,303 Da, encodes a 1,015-amino acid polypeptide with a single transmembrane region and 1 putative tyrosine phosphatase catalytic domain. The authors found phogrin to share 74% identity with the ICA512/IA2 cytoplasmic domain, but only 29% identity with the luminal domain. 48% (37 of 77) and 61% (47 of 77) of sera from new-onset patients with type I diabetes were positive for autoantibodies to full-length and the cytoplasmic domain of phogrin, respectively.
Lu et al. (1996) isolated the mouse gene for IAR, termed IA2-beta. Many IDDM sera are known to immunoprecipitate 37-kD and 40-kD tryptic fragments from islet cells. Lu et al. (1996) showed that IA2-beta and IA2 are the precursors of the 37-kD and 40-kD islet cell autoantigens, respectively.
After administration of ghrelin (605353), Doi et al. (2006) observed increases in Ia2-beta in mouse brain, pancreas, and insulinoma cell lines, but not Ia2. Administration of ghrelin or Ia2-beta overexpression inhibited glucose-stimulated insulin secretion in insulinoma cells, and inhibition of Ia2-beta overexpression by RNA interference ameliorated ghrelin's inhibitory effects on glucose-stimulated insulin secretion. Doi et al. (2006) suggested that the inhibitory effects of ghrelin on glucose-stimulated insulin secretion are at least partly due to increased expression of Ia2-beta induced by ghrelin.
By FISH analysis, Smith et al. (1996) mapped the PTPRN2 gene to chromosome 7q36. Morahan et al. (1998) provided refined mapping of the PTPRN and PTPRN2 genes on the high-resolution radiation hybrid map of chromosomes 2 and 7, respectively.
Cui, L., Yu, W.-P., De Aizpurua, H. J., Schmidli, R. S., Pallen, C. J. Cloning and characterization of islet cell antigen-related protein-tyrosine phosphatase (PTP), a novel receptor-like PTP and autoantigen in insulin-dependent diabetes. J. Biol. Chem. 271: 24817-24823, 1996. [PubMed: 8798755]
Doi, A., Shono, T., Nishi, M., Furuta, H., Sasaki, H., Nanjo, K. IA-2-beta, but not IA-2, is induced by ghrelin and inhibits glucose-stimulated insulin secretion. Proc. Nat. Acad. Sci. 103: 885-890, 2006. [PubMed: 16418280] [Full Text: https://doi.org/10.1073/pnas.0502470102]
Kawasaki, E., Hutton, J. C., Eisenbarth, G. S. Molecular cloning and characterization of the human transmembrane protein tyrosine phosphatase homologue, phogrin, an autoantigen of type 1 diabetes. Biochem. Biophys. Res. Commun. 227: 440-447, 1996. [PubMed: 8878534] [Full Text: https://doi.org/10.1006/bbrc.1996.1526]
Lu, J., Li, Q., Xie, H., Chen, Z.-J., Borovitskaya, A. E., Maclaren, N. K., Notkins, A. L., Lan, M. S. Identification of a second transmembrane protein tyrosine phosphatase, IA-2-beta, as an autoantigen in insulin-dependent diabetes mellitus: precursor of the 37-kDa tryptic fragment. Proc. Nat. Acad. Sci. 93: 2307-2311, 1996. [PubMed: 8637868] [Full Text: https://doi.org/10.1073/pnas.93.6.2307]
Morahan, G., Huang, D., Yu, W.-P., Cui, L., DeAizpurua, H., Pallen, C. J. Localization of the genes encoding the type I diabetes autoantigens, protein-tyrosine phosphatases IA2 and IAR. Mammalian Genome 9: 593-594, 1998. [PubMed: 9657860] [Full Text: https://doi.org/10.1007/s003359900824]
Smith, P. D., Barker, K. T., Wang, J., Lu, Y. J., Shipley, J., Crompton, M. R. ICAAR a novel member of a new family of transmembrane, tyrosine phosphatase-like proteins. Biochem. Biophys. Res. Commun. 229: 402-411, 1996. [PubMed: 8954911] [Full Text: https://doi.org/10.1006/bbrc.1996.1817]
Wasmeier, C, Hutton, J. C. Molecular cloning of phogrin, a protein-tyrosine phosphatase homologue localized to insulin secretory granule membranes. J. Biol. Chem. 271: 18161-18170, 1996. [PubMed: 8663434] [Full Text: https://doi.org/10.1074/jbc.271.30.18161]