PTPN2 explained

Tyrosine-protein phosphatase non-receptor type 2 is an enzyme that in humans is encoded by the PTPN2 gene.^{[1] [2]}

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation.

Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling. Three alternatively spliced variants of this gene, which encode isoforms differing at their extreme C-termini, have been described.

The different C-termini are thought to determine the substrate specificity, as well as the cellular localization of the isoforms. Two highly related but distinctly processed pseudogenes that localize to distinct chromosomes have been reported.

Further reading

• Baumgartner, CK, Ebrahimi-Nik, H, Iracheta-Vellve, A. The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity. . Nature . 2023. 622 . 7984 . 850–862 . 10.1038/s41586-023-06575-7. 37794185 . 10599993 . 2023Natur.622..850B . free .
• LaFleur MW, Nguyen TH, Coxe MA. PTPN2 regulates the generation of exhausted CD8+ T cell subpopulations and restrains tumor immunity. . Nat. Immunol. . 2019. 20 . 10 . 1335–1347 . 10.1038/s41590-019-0480-4. 31527834 . free . 6754306.
• Manguso RT, Pope HW, Zimmer MD . In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. . Nature . 2017. 547 . 7664 . 413–418 . 10.1038/nature23270. 28723893 . free . 5924693 .
• Mosinger B, Tillmann U, Westphal H, Tremblay ML . Cloning and characterization of a mouse cDNA encoding a cytoplasmic protein-tyrosine-phosphatase. . Proc. Natl. Acad. Sci. U.S.A. . 89 . 2 . 499–503 . 1992 . 1731319 . 10.1073/pnas.89.2.499 . 48266 . 1992PNAS...89..499M . free .
• Swarup G, Kamatkar S, Radha V, Rema V . Molecular cloning and expression of a protein-tyrosine phosphatase showing homology with transcription factors Fos and Jun. . FEBS Lett. . 280 . 1 . 65–9 . 1991 . 1849097 . 10.1016/0014-5793(91)80205-H . 10568838 . free . 1991FEBSL.280...65S .
• Cool DE, Tonks NK, Charbonneau H, etal . cDNA isolated from a human T-cell library encodes a member of the protein-tyrosine-phosphatase family. . Proc. Natl. Acad. Sci. U.S.A. . 86 . 14 . 5257–61 . 1989 . 2546150 . 10.1073/pnas.86.14.5257 . 297600 . 1989PNAS...86.5257C . free .
• Lorenzen JA, Dadabay CY, Fischer EH . COOH-terminal sequence motifs target the T cell protein tyrosine phosphatase to the ER and nucleus. . J. Cell Biol. . 131 . 3 . 631–43 . 1995 . 7593185 . 10.1083/jcb.131.3.631 . 2120615 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Johnson CV, Cool DE, Glaccum MB, etal . Isolation and mapping of human T-cell protein tyrosine phosphatase sequences: localization of genes and pseudogenes discriminated using fluorescence hybridization with genomic versus cDNA probes. . Genomics . 16 . 3 . 619–29 . 1993 . 8325634 . 10.1006/geno.1993.1239 .
• Tiganis T, Flint AJ, Adam SA, Tonks NK . Association of the T-cell protein tyrosine phosphatase with nuclear import factor p97. . J. Biol. Chem. . 272 . 34 . 21548–57 . 1997 . 9261175 . 10.1074/jbc.272.34.21548 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Tiganis T, Bennett AM, Ravichandran KS, Tonks NK . Epidermal growth factor receptor and the adaptor protein p52Shc are specific substrates of T-cell protein tyrosine phosphatase. . Mol. Cell. Biol. . 18 . 3 . 1622–34 . 1998 . 9488479 . 10.1128/MCB.18.3.1622. 108877 .
• Tiganis T, Kemp BE, Tonks NK . The protein-tyrosine phosphatase TCPTP regulates epidermal growth factor receptor-mediated and phosphatidylinositol 3-kinase-dependent signaling. . J. Biol. Chem. . 274 . 39 . 27768–75 . 1999 . 10488121 . 10.1074/jbc.274.39.27768 . free .
• Iversen LF, Moller KB, Pedersen AK, etal . Structure determination of T cell protein-tyrosine phosphatase. . J. Biol. Chem. . 277 . 22 . 19982–90 . 2002 . 11907034 . 10.1074/jbc.M200567200 . free .
• Simoncic PD, Lee-Loy A, Barber DL, etal . The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3. . Curr. Biol. . 12 . 6 . 446–53 . 2002 . 11909529 . 10.1016/S0960-9822(02)00697-8 . 16693906 . free . 2002CBio...12..446S .
• ten Hoeve J, de Jesus Ibarra-Sanchez M, Fu Y, etal . Identification of a nuclear Stat1 protein tyrosine phosphatase. . Mol. Cell. Biol. . 22 . 16 . 5662–8 . 2002 . 12138178 . 10.1128/MCB.22.16.5662-5668.2002 . 133976 .
• Zhu W, Mustelin T, David M . Arginine methylation of STAT1 regulates its dephosphorylation by T cell protein tyrosine phosphatase. . J. Biol. Chem. . 277 . 39 . 35787–90 . 2002 . 12171910 . 10.1074/jbc.C200346200 . free .
• Yamamoto T, Sekine Y, Kashima K, etal . The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation. . Biochem. Biophys. Res. Commun. . 297 . 4 . 811–7 . 2002 . 12359225 . 10.1016/S0006-291X(02)02291-X . 2115/28124 . free .
• Gupta S, Radha V, ((Sudhakar Ch)), Swarup G . A nuclear protein tyrosine phosphatase activates p53 and induces caspase-1-dependent apoptosis. . FEBS Lett. . 532 . 1–2 . 61–6 . 2003 . 12459463 . 10.1016/S0014-5793(02)03628-1 . 33468275 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Galic S, Klingler-Hoffmann M, Fodero-Tavoletti MT, etal . Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP. . Mol. Cell. Biol. . 23 . 6 . 2096–108 . 2003 . 12612081 . 10.1128/MCB.23.6.2096-2108.2003 . 149470 .

Notes and References

1. Brown-Shimer S, Johnson KA, Lawrence JB, Johnson C, Bruskin A, Green NR, Hill DE . Molecular cloning and chromosome mapping of the human gene encoding protein phosphotyrosyl phosphatase 1B . Proc Natl Acad Sci U S A . 87 . 13 . 5148–52 . Aug 1990 . 2164224 . 54279 . 10.1073/pnas.87.13.5148 . 1990PNAS...87.5148B . free .
2. Web site: Entrez Gene: PTPN2 protein tyrosine phosphatase, non-receptor type 2.