Disease relevance of Ptprn

• The intracellular domain is 376 amino acids long and 74% identical to the intracellular domain of IA-2, a major autoantigen in insulin-dependent diabetes mellitus (IDDM) [1].
• Disruption of the transmembrane dense core vesicle proteins IA-2 and IA-2beta causes female infertility [2].
• Catalytic activities and mutagen activation ability of the human enzyme were assessed and directly compared with results obtained with the orthologous mouse IA2, which was also expressed using vaccinia virus [3].
• The expression of IA-2/PTP35 messages was detected by northern blot analysis in MIN6N8 cells, an insulinoma cell line derived from non-obese diabetic mice, but its expression level was not affected by the ambient glucose level, phorbol-12-myristate 13-acetate or tumour necrosis factor-alpha [4].

High impact information on Ptprn

• IA-2beta, but not IA-2, is induced by ghrelin and inhibits glucose-stimulated insulin secretion [5].
• A partial sequence of the extracellular domain of IA-2beta indicates that it differs substantially (only 26% identical) from that of IA-2 [1].
• With regard to the phase I pathway, the cells expressed various P-450 (class IA, IA2, IIB, IIE1, IIIA) and flavin adenine dinucleotide-containing monooxygenase-dependent bio-transformation enzyme activities at levels (in lines C2.8 and C6) comparable with those present in murine adult liver preparations [6].
• In the present study, by mating C57BL/6Nci IA-2(+/-) with IA-2beta(+/-) mice, we generated double knockout mice (IA-2(-/-)/IA-2beta(-/-)) to study the effect of the combined deletion of these two proteins on insulin secretion and blood glucose levels [7].
• Dense Core Vesicle Proteins IA-2 and IA-2{beta}: Metabolic Alterations in Double Knockout Mice [7].

Biological context of Ptprn

• Because the nucleotide sequence of human and mouse IA-2 cDNA are closely related, it seemed likely that the genomic organization of the two molecules would be similar [8].
• Mouse IA-2 encompasses approximately 20 kb and encodes 23 exons [8].
• RESULTS: The mouse IA-2 gene and the 5' upstream regulatory region were isolated and the intron-exon junctions determined [8].
• METHODS: IA-2 cDNA was used to screen a 129SVJ mouse genomic library [8].
• The region around the major transcription start site of mouse IA-2 is similar to human IA-2 and other transmembrane protein tyrosine phosphatases [8].

Anatomical context of Ptprn

• CONCLUSIONS: These three central nervous system genes (Znf142, Ptprn, and Znf133) represent promising candidates for involvement in the differential sensitivity to alcohol exhibited between ILS and ISS mice [9].
• IA-2 and IA-2beta are members of the transmembrane protein tyrosine phosphatase family located in dense core vesicles of neuroendocrine cells, including the beta-cells of pancreatic islets [7].
• We concluded that the initial T-cell response to phogrin is restricted to a small number of dominant peptides and that it subsequently spreads to other regions of the molecule, including those containing the major humoral epitopes that are highly conserved between IA-2 and phogrin [10].
• Expression of PTP35, the murine homologue of the protein tyrosine phosphatase-related sequence IA-2, is regulated during cell growth and stimulated by mitogens in 3T3 fibroblasts [11].
• Expression of protein tyrosine phosphatase-like molecule ICA512/IA-2 induces growth arrest in yeast cells and transfected mammalian cell lines [12].

Associations of Ptprn with chemical compounds

• In both human and mouse IA-2, several substitutions were found in the highly conserved regions including an Ala to Asp substitution in the core sequence [13].
• With regard to phase-I pathway, the expression of various P450-like activities (IA1, IA2, IIB1, IIE1, IIIA P450 classes) and thiobenzamide s-oxidase (as FAD-MFO marker), were examined in terms of their exact incubation conditions for the LMA during a period of preincubation (1 h) over the tau range 0.06-1.40 [14].
• (p40)2 administration to NOD mice inhibits interferon-gamma but not IL-10 production in response to lipopolysaccharide (LPS) or to the putative autoantigen IA-2 [15].
• Mouse IA2 was five- to sevenfold more active than the human enzyme for activation of the procarcinogens 2-acetylaminofluorene and benzo[a]pyrene-trans-7,8-dihydrodiol and the promutagens Glu-P-2 and Trp-P-1 [3].
• Mouse IA2 also catalyzed ethoxyresorufin O-deethylation, and its activity was sevenfold greater than expressed human IA2 [3].

Regulatory relationships of Ptprn

• In conclusion, we have identified IA-2 peptides that induce lymphoproliferative responses in DQ8 transgenic and NOD mice and shown that these peptides stimulate production of Th1 and Th2 cytokines [16].

Other interactions of Ptprn

• However, the expression of IA-2, another structurally related beta-cell autoantigen, was not induced by ghrelin [5].
• Targeted disruption of the protein tyrosine phosphatase-like molecule IA-2 results in alterations in glucose tolerance tests and insulin secretion [17].

Analytical, diagnostic and therapeutic context of Ptprn

• Northern and Western blot analysis showed that neither IA-2 mRNA nor protein was expressed [17].
• Physical examination of the IA-2(- /-) animals and histological examination of tissues failed to reveal any abnormalities [17].
• In the pituitary, IA-2 mRNA was located in the anterior and posterior pituitary by in situ hybridization [18].
• The pattern of IA-2 mRNA expression in normal male mouse brain at 1, 4, and 8 weeks of age by the Northern blot analysis was similar to that in the pituitary by RT-PCR analysis [18].
• Cytochromes P450IA1 and IA2 were purified from hepatic microsomes from 3-methylcholanthrene (MC)-treated C57BL/6 mice, using a combination of affinity chromatography and high performance liquid chromatography [19].

References