The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PTPRN  -  protein tyrosine phosphatase, receptor...

Homo sapiens

Synonyms: IA-2, IA-2/PTP, IA2, ICA 512, ICA3, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PTPRN

  • Islet cell Ag 512 (ICA512) is a recombinant human Ag that was isolated from an islet cDNA expression library by screening with human insulin-dependent diabetes mellitus sera [1].
  • Following phage display characterization of ICA512 autoantigenic epitopes, we developed fluid phase autoantibody radioimmunoassays for a series of ICA512 fragments (F1 [amino acids (aa): 761-964], F2A [aa 256-760], F2B [aa 761-928], and F2C [aa 929-979]) [2].
  • A novel 3.6-kb cDNA, IA-2, with a 2,937-bp open reading frame was isolated from a human insulinoma subtraction library (ISL-153) [3].
  • The biotinylated cytoplasmic domain of IA-2 expressed in Escherichia coli was used as an antigen [4].
  • Through this process, we have been able to identify preparations of GAD65 and IA-2, generated in insect cells using the baculovirus expression system, that stimulate relevant clones and display low inhibitory effects on third-party antigens [5].

High impact information on PTPRN


Chemical compound and disease context of PTPRN


Biological context of PTPRN

  • Assignment of the human gene for receptor-type protein tyrosine phosphatase IA-2 (PTPRN) to chromosome region 2q35 --> q36.1 and identification of an intragenic genetic marker [14].
  • Using a mouse protein tyrosine phosphatase cDNA fragment as a probe, cosmid clones containing segments of the human IA-2 PTPase gene (PTPRN) were isolated [14].
  • IA-2 (islet cell antigen 512) is the primary target of humoral autoimmunity against type 1 diabetes-associated tyrosine phosphatase autoantigens [15].
  • MATERIALS AND METHODS: To determine the proteins with which IA-2 interacts, a yeast two-hybrid system was used to screen a human foetal library, and deletion mutants were used to determine the binding sites [16].
  • The physiological role(s) of these proteins remain poorly defined, although recent studies indicate that IA-2 may be involved in granule trafficking and exocytosis [17].

Anatomical context of PTPRN


Associations of PTPRN with chemical compounds

  • These results indicate that the expression of ICA512/phogrin-A and cytoplasmic ICA is less in patients identified by urinary glucose testing but indicate that with combined autoantibody testing 90% of patients can be identified independent of the mode of diagnosis [20].
  • Phogrin is 74% identical to the ICA512/IA-2 autoantigen of type 1 diabetes in the cytoplasmic domain, but only 29% in the luminal domain [21].
  • Similarly to calpeptin, okadaic acid inhibits ICA512 proteolysis and insulin secretion [22].
  • These findings indicate that glutamine at position 862, and residues 876-880 of the WPD loop of IA-2 are important for several of the IA-2 specific PTP domain epitopes [23].
  • Both cleavage sites are immediately after an arginine residue at position 653 for IA-2 and position 679 for IA-2 beta [24].

Physical interactions of PTPRN


Other interactions of PTPRN

  • In the 17 relatives who developed type 1 diabetes, progression to disease was associated with reactivity to multiple IA-2/IA-2 beta epitopes [15].
  • These data suggest that IA-2 is the primary phosphatase-like autoantigen associated with type 1 diabetes and that studying autoantibody epitope diversity may assist in disease prediction [15].
  • Dephosphorylation of beta2-syntrophin and Ca2+/mu-calpain-mediated cleavage of ICA512 upon stimulation of insulin secretion [22].
  • We report the identification of betaIV spectrin, a novel spectrin isolated as an interactor of the receptor tyrosine phosphatase-like protein ICA512 [26].
  • This cleavage occurs at the plasma membrane and generates an ICA512 cytosolic fragment that is targeted to the nucleus, where it binds the E3-SUMO ligase protein inhibitor of activated signal transducer and activator of transcription-y (PIASy) and up-regulates insulin expression [19].

Analytical, diagnostic and therapeutic context of PTPRN


  1. Islet cell antigen 512 is a diabetes-specific islet autoantigen related to protein tyrosine phosphatases. Rabin, D.U., Pleasic, S.M., Shapiro, J.A., Yoo-Warren, H., Oles, J., Hicks, J.M., Goldstein, D.E., Rae, P.M. J. Immunol. (1994) [Pubmed]
  2. ICA512(IA-2) epitope specific assays distinguish transient from diabetes associated autoantibodies. Miao, D., Yu, L., Tiberti, C., Cuthbertson, D.D., Rewers, M., di Mario, U., Eisenbarth, G.S., Dotta, F. J. Autoimmun. (2002) [Pubmed]
  3. Molecular cloning and identification of a receptor-type protein tyrosine phosphatase, IA-2, from human insulinoma. Lan, M.S., Lu, J., Goto, Y., Notkins, A.L. DNA Cell Biol. (1994) [Pubmed]
  4. Autoantibodies to IA-2 in type 1 diabetes: measurements with a new enzyme-linked immunosorbent assay. Kawasaki, E., Yamaguchi, H., Hattori, H., Egashira, T., Eguchi, K. Ann. N. Y. Acad. Sci. (2002) [Pubmed]
  5. Characterization of preparations of GAD65, proinsulin, and the islet tyrosine phosphatase IA-2 for use in detection of autoreactive T-cells in type 1 diabetes: report of phase II of the Second International Immunology of Diabetes Society Workshop for Standardization of T-cell assays in type 1 diabetes. Peakman, M., Tree, T.I., Endl, J., van Endert, P., Atkinson, M.A., Roep, B.O. Diabetes (2001) [Pubmed]
  6. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Pugliese, A., Zeller, M., Fernandez, A., Zalcberg, L.J., Bartlett, R.J., Ricordi, C., Pietropaolo, M., Eisenbarth, G.S., Bennett, S.T., Patel, D.D. Nat. Genet. (1997) [Pubmed]
  7. Lack of association between early exposure to cow's milk protein and beta-cell autoimmunity. Diabetes Autoimmunity Study in the Young (DAISY). Norris, J.M., Beaty, B., Klingensmith, G., Yu Liping, n.u.l.l., Hoffman, M., Chase, H.P., Erlich, H.A., Hamman, R.F., Eisenbarth, G.S., Rewers, M. JAMA (1996) [Pubmed]
  8. Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes. Aanstoot, H.J., Kang, S.M., Kim, J., Lindsay, L.A., Roll, U., Knip, M., Atkinson, M., Mose-Larsen, P., Fey, S., Ludvigsson, J., Landin, L., Bruining, J., Maclaren, N., Akerblom, H.K., Baekkeskov, S. J. Clin. Invest. (1996) [Pubmed]
  9. Humoral autoreactivity to an alternatively spliced variant of ICA512/IA-2 in Type I diabetes. Park, Y.S., Kawasaki, E., Kelemen, K., Yu, L., Schiller, M.R., Rewers, M., Mizuta, M., Eisenbarth, G.S., Hutton, J.C. Diabetologia (2000) [Pubmed]
  10. Autoantibodies to ICA12 (SOX-13) are not specific for Type I diabetes. Steinbrenner, H., Lohmann, T., Ostendorf, B., Scherbaum, W.A., Seissler, J. Diabetologia (2000) [Pubmed]
  11. Low prevalence of islet autoimmunity in adult diabetes and low predictive value of islet autoantibodies in the general adult population of northern Italy. Bosi, E.P., Garancini, M.P., Poggiali, F., Bonifacio, E., Gallus, G. Diabetologia (1999) [Pubmed]
  12. Transmembrane protein tyrosine phosphatase IA-2 (ICA512) is expressed in human midgut carcinoids but is not detectable in normal enterochromaffin cells. Cunningham, J.L., Lopez-Egido, J.R., Janson, E.T., Eriksson, B., Oberg, K., Gobl, A.E. J. Endocrinol. (2000) [Pubmed]
  13. Utility of ribotyping, restriction endonuclease analysis and pulsed-field gel electrophoresis to discriminate between isolates of Neisseria gonorrhoeae of serovar IA-2 which require arginine, hypoxanthine or uracil for growth. Li, H., Dillon, J.A. J. Med. Microbiol. (1995) [Pubmed]
  14. Assignment of the human gene for receptor-type protein tyrosine phosphatase IA-2 (PTPRN) to chromosome region 2q35 --> q36.1 and identification of an intragenic genetic marker. van den Maagdenberg, A.M., Olde Weghuis, D., Rijss, J., van de Wetering, R.A., Wieringa, B., Geurts van Kessel, A., Hendriks, W.J. Cytogenet. Cell Genet. (1996) [Pubmed]
  15. IA-2 (islet cell antigen 512) is the primary target of humoral autoimmunity against type 1 diabetes-associated tyrosine phosphatase autoantigens. Bonifacio, E., Lampasona, V., Bingley, P.J. J. Immunol. (1998) [Pubmed]
  16. The IA-2 interactome. Hu, Y.F., Zhang, H.L., Cai, T., Harashima, S., Notkins, A.L. Diabetologia (2005) [Pubmed]
  17. A novel strategy for the development of selective active-site inhibitors of the protein tyrosine phosphatase-like proteins islet-cell antigen 512 (IA-2) and phogrin (IA-2beta). Drake, P.G., Peters, G.H., Andersen, H.S., Hendriks, W., Møller, N.P. Biochem. J. (2003) [Pubmed]
  18. ICA 512, an autoantigen of type I diabetes, is an intrinsic membrane protein of neurosecretory granules. Solimena, M., Dirkx, R., Hermel, J.M., Pleasic-Williams, S., Shapiro, J.A., Caron, L., Rabin, D.U. EMBO J. (1996) [Pubmed]
  19. Nuclear translocation of an ICA512 cytosolic fragment couples granule exocytosis and insulin expression in {beta}-cells. Trajkovski, M., Mziaut, H., Altkrüger, A., Ouwendijk, J., Knoch, K.P., Müller, S., Solimena, M. J. Cell Biol. (2004) [Pubmed]
  20. Autoantibodies to multiple islet autoantigens in patients with abrupt onset type 1 diabetes and diabetes diagnosed with urinary glucose screening. Sera, Y., Kawasaki, E., Abiru, N., Ozaki, M., Abe, T., Takino, H., Kondo, H., Yamasaki, H., Yamaguchi, Y., Akazawa, S., Nagataki, S., Uchigata, Y., Matsuura, N., Eguchi, K. J. Autoimmun. (1999) [Pubmed]
  21. Molecular cloning and characterization of the human transmembrane protein tyrosine phosphatase homologue, phogrin, an autoantigen of type 1 diabetes. Kawasaki, E., Hutton, J.C., Eisenbarth, G.S. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  22. Dephosphorylation of beta2-syntrophin and Ca2+/mu-calpain-mediated cleavage of ICA512 upon stimulation of insulin secretion. Ort, T., Voronov, S., Guo, J., Zawalich, K., Froehner, S.C., Zawalich, W., Solimena, M. EMBO J. (2001) [Pubmed]
  23. Fine mapping of diabetes-associated IA-2 specific autoantibodies. Bearzatto, M., Lampasona, V., Belloni, C., Bonifacio, E. J. Autoimmun. (2003) [Pubmed]
  24. Autoantibodies to IA-2 and IA-2 beta in insulin-dependent diabetes mellitus recognize conformational epitopes: location of the 37- and 40-kDa fragments determined. Xie, H., Zhang, B., Matsumoto, Y., Li, Q., Notkins, A.L., Lan, M.S. J. Immunol. (1997) [Pubmed]
  25. The receptor tyrosine phosphatase-like protein ICA512 binds the PDZ domains of beta2-syntrophin and nNOS in pancreatic beta-cells. Ort, T., Maksimova, E., Dirkx, R., Kachinsky, A.M., Berghs, S., Froehner, S.C., Solimena, M. Eur. J. Cell Biol. (2000) [Pubmed]
  26. betaIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous system. Berghs, S., Aggujaro, D., Dirkx, R., Maksimova, E., Stabach, P., Hermel, J.M., Zhang, J.P., Philbrick, W., Slepnev, V., Ort, T., Solimena, M. J. Cell Biol. (2000) [Pubmed]
  27. BCG vaccination and GAD65 and IA-2 autoantibodies in autoimmune diabetes in southern India. Sanjeevi, C.B., Das, A.K., Shtauvere-Brameus, A. Ann. N. Y. Acad. Sci. (2002) [Pubmed]
WikiGenes - Universities