PTPN2

PTPN2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1L8K
Identifiers
Aliases	PTPN2 , PTN2, PTPT, TC-PTP, TCELLPTP, TCPTP, protein tyrosine phosphatase, non-receptor type 2, protein tyrosine phosphatase non-receptor type 2
External IDs	OMIM: 176887 MGI: 97806 HomoloGene: 7497 GeneCards: PTPN2
Gene location (Human) Chr. Chromosome 18 (human) [1] Band 18p11.21 Start 12,785,478 bp [1] End 12,929,643 bp [1]
Gene location (Mouse) Chr. Chromosome 18 (mouse) [2] Band 18|18 E1 Start 67,798,581 bp [2] End 67,857,665 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte thymus parotid gland oocyte lymph node body of pancreas thymus cerebellar hemisphere minor salivary gland bone marrow cells Top expressed in otic placode saccule condyle fossa Paneth cell hair follicle secondary oocyte submandibular gland primitive streak vas deferens More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding protein kinase binding phosphatase activity integrin binding phosphoprotein phosphatase activity syntaxin binding non-membrane spanning protein tyrosine phosphatase activity receptor tyrosine kinase binding hydrolase activity protein tyrosine phosphatase activity STAT family protein binding Cellular component cytoplasm membrane plasma membrane endoplasmic reticulum nucleus endoplasmic reticulum-Golgi intermediate compartment nucleoplasm cytosol Biological process negative regulation of type I interferon-mediated signaling pathway negative regulation of epidermal growth factor receptor signaling pathway positive regulation of PERK-mediated unfolded protein response dephosphorylation negative regulation of interleukin-4-mediated signaling pathway positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway negative regulation of interleukin-6-mediated signaling pathway negative regulation of cell population proliferation protein dephosphorylation negative regulation of interleukin-2-mediated signaling pathway regulation of interferon-gamma-mediated signaling pathway negative regulation of protein tyrosine kinase activity regulation of hepatocyte growth factor receptor signaling pathway negative regulation of platelet-derived growth factor receptor-beta signaling pathway insulin receptor signaling pathway negative regulation of interferon-gamma-mediated signaling pathway glucose homeostasis negative regulation of chemotaxis negative regulation of tumor necrosis factor-mediated signaling pathway negative regulation of macrophage differentiation negative regulation of T cell receptor signaling pathway negative regulation of positive thymic T cell selection negative regulation of insulin receptor signaling pathway T cell differentiation negative regulation of ERK1 and ERK2 cascade erythrocyte differentiation negative regulation of lipid storage B cell differentiation peptidyl-tyrosine dephosphorylation positive regulation of gluconeogenesis negative regulation of macrophage colony-stimulating factor signaling pathway negative regulation of inflammatory response negative regulation of transcription by RNA polymerase II negative regulation of tyrosine phosphorylation of STAT protein cellular response to cytokine stimulus Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5771 19255 Ensembl ENSG00000175354 ENSMUSG00000024539 UniProt P17706 Q06180 RefSeq (mRNA) NM_001207013 NM_001308287 NM_002828 NM_080422 NM_080423 NM_001127177 NM_008977 RefSeq (protein) NP_001193942 NP_001295216 NP_002819 NP_536347 NP_536348 NP_001120649 NP_033003 Location (UCSC) Chr 18: 12.79 – 12.93 Mb Chr 18: 67.8 – 67.86 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Tyrosine-protein phosphatase non-receptor type 2 is an enzyme that in humans is encoded by the PTPN2 gene. ^{[5] [6]}

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. ^[6]

References

1. GRCh38: Ensembl release 89: ENSG00000175354 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024539 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Brown-Shimer S, Johnson KA, Lawrence JB, Johnson C, Bruskin A, Green NR, Hill DE (Aug 1990). "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. Bibcode:1990PNAS...87.5148B. doi: 10.1073/pnas.87.13.5148 . PMC   54279 . PMID   2164224.
6. "Entrez Gene: PTPN2 protein tyrosine phosphatase, non-receptor type 2".

Further reading

• Baumgartner, CK, Ebrahimi-Nik, H, Iracheta-Vellve, A (2023). "The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity". Nature. 622 (7984): 850–862. Bibcode:2023Natur.622..850B. doi: 10.1038/s41586-023-06575-7 . PMC   10599993 . PMID   37794185.
• LaFleur MW, Nguyen TH, Coxe MA (2019). "PTPN2 regulates the generation of exhausted CD8+ T cell subpopulations and restrains tumor immunity". Nat. Immunol. 20 (10): 1335–1347. doi: 10.1038/s41590-019-0480-4 . PMC   6754306 . PMID   31527834.
• Manguso RT, Pope HW, Zimmer MD (2017). "In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target". Nature. 547 (7664): 413–418. doi: 10.1038/nature23270 . PMC   5924693 . PMID   28723893.
• Mosinger B, Tillmann U, Westphal H, Tremblay ML (1992). "Cloning and characterization of a mouse cDNA encoding a cytoplasmic protein-tyrosine-phosphatase". Proc. Natl. Acad. Sci. U.S.A. 89 (2): 499–503. Bibcode:1992PNAS...89..499M. doi: 10.1073/pnas.89.2.499 . PMC   48266 . PMID   1731319.
• Swarup G, Kamatkar S, Radha V, Rema V (1991). "Molecular cloning and expression of a protein-tyrosine phosphatase showing homology with transcription factors Fos and Jun". FEBS Lett. 280 (1): 65–9. doi: 10.1016/0014-5793(91)80205-H . PMID   1849097. S2CID   10568838.
• Cool DE, Tonks NK, Charbonneau H, et al. (1989). "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. Bibcode:1989PNAS...86.5257C. doi: 10.1073/pnas.86.14.5257 . PMC   297600 . PMID   2546150.
• Lorenzen JA, Dadabay CY, Fischer EH (1995). "COOH-terminal sequence motifs target the T cell protein tyrosine phosphatase to the ER and nucleus". J. Cell Biol. 131 (3): 631–43. doi:10.1083/jcb.131.3.631. PMC   2120615 . PMID   7593185.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.
• Johnson CV, Cool DE, Glaccum MB, et al. (1993). "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. doi:10.1006/geno.1993.1239. PMID   8325634.
• Tiganis T, Flint AJ, Adam SA, Tonks NK (1997). "Association of the T-cell protein tyrosine phosphatase with nuclear import factor p97". J. Biol. Chem. 272 (34): 21548–57. doi: 10.1074/jbc.272.34.21548 . PMID   9261175.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID   9373149.
• Tiganis T, Bennett AM, Ravichandran KS, Tonks NK (1998). "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. doi:10.1128/MCB.18.3.1622. PMC   108877 . PMID   9488479.
• Tiganis T, Kemp BE, Tonks NK (1999). "The protein-tyrosine phosphatase TCPTP regulates epidermal growth factor receptor-mediated and phosphatidylinositol 3-kinase-dependent signaling". J. Biol. Chem. 274 (39): 27768–75. doi: 10.1074/jbc.274.39.27768 . PMID   10488121.
• Aoki N, Matsuda T (2002). "A nuclear protein tyrosine phosphatase TC-PTP is a potential negative regulator of the PRL-mediated signaling pathway: dephosphorylation and deactivation of signal transducer and activator of transcription 5a and 5b by TC-PTP in nucleus". Mol. Endocrinol. 16 (1): 58–69. doi: 10.1210/mend.16.1.0761 . PMID   11773439.
• Iversen LF, Moller KB, Pedersen AK, et al. (2002). "Structure determination of T cell protein-tyrosine phosphatase". J. Biol. Chem. 277 (22): 19982–90. doi: 10.1074/jbc.M200567200 . PMID   11907034.
• Simoncic PD, Lee-Loy A, Barber DL, et al. (2002). "The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3". Curr. Biol. 12 (6): 446–53. Bibcode:2002CBio...12..446S. doi: 10.1016/S0960-9822(02)00697-8 . PMID   11909529. S2CID   16693906.
• ten Hoeve J, de Jesus Ibarra-Sanchez M, Fu Y, et al. (2002). "Identification of a nuclear Stat1 protein tyrosine phosphatase". Mol. Cell. Biol. 22 (16): 5662–8. doi:10.1128/MCB.22.16.5662-5668.2002. PMC   133976 . PMID   12138178.
• Zhu W, Mustelin T, David M (2002). "Arginine methylation of STAT1 regulates its dephosphorylation by T cell protein tyrosine phosphatase". J. Biol. Chem. 277 (39): 35787–90. doi: 10.1074/jbc.C200346200 . PMID   12171910.
• Yamamoto T, Sekine Y, Kashima K, et al. (2002). "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. doi:10.1016/S0006-291X(02)02291-X. hdl: 2115/28124 . PMID   12359225.
• Gupta S, Radha V, Sudhakar Ch, Swarup G (2003). "A nuclear protein tyrosine phosphatase activates p53 and induces caspase-1-dependent apoptosis". FEBS Lett. 532 (1–2): 61–6. doi: 10.1016/S0014-5793(02)03628-1 . PMID   12459463. S2CID   33468275.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Galic S, Klingler-Hoffmann M, Fodero-Tavoletti MT, et al. (2003). "Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP". Mol. Cell. Biol. 23 (6): 2096–108. doi:10.1128/MCB.23.6.2096-2108.2003. PMC   149470 . PMID   12612081.