NameTyrosine-protein phosphatase non-receptor type 2
Synonyms
  • 3.1.3.48
  • PTPT
  • T-cell protein-tyrosine phosphatase
  • TCPTP
Gene NamePTPN2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009001|Tyrosine-protein phosphatase non-receptor type 2
MPTTIEREFEELDTQRRWQPLYLEIRNESHDYPHRVAKFPENRNRNRYRDVSPYDHSRVK
LQNAENDYINASLVDIEEAQRSYILTQGPLPNTCCHFWLMVWQQKTKAVVMLNRIVEKES
VKCAQYWPTDDQEMLFKETGFSVKLLSEDVKSYYTVHLLQLENINSGETRTISHFHYTTW
PDFGVPESPASFLNFLFKVRESGSLNPDHGPAVIHCSAGIGRSGTFSLVDTCLVLMEKGD
DINIKQVLLNMRKYRMGLIQTPDQLRFSYMAIIEGAKCIKGDSSIQKRWKELSKEDLSPA
FDHSPNKIMTEKYNGNRIGLEEEKLTGDRCTGLSSKMQDTMEENSESALRKRIREDRKAT
TAQKVQQMKQRLNENERKRKRWLYWQPILTKMGFMSVILVGAFVGWTLFFQQNAL
Number of residues415
Molecular Weight48472.94
Theoretical pINot Available
GO Classification
Functions
  • protein kinase binding
  • receptor tyrosine kinase binding
  • protein tyrosine phosphatase activity
  • integrin binding
  • syntaxin binding
Processes
  • negative regulation of interleukin-6-mediated signaling pathway
  • cytokine-mediated signaling pathway
  • negative regulation of type I interferon-mediated signaling pathway
  • negative regulation of tyrosine phosphorylation of Stat1 protein
  • negative regulation of tyrosine phosphorylation of Stat5 protein
  • negative regulation of protein tyrosine kinase activity
  • negative regulation of chemotaxis
  • negative regulation of tyrosine phosphorylation of Stat6 protein
  • negative regulation of T cell receptor signaling pathway
  • interferon-gamma-mediated signaling pathway
  • positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
  • T cell differentiation
  • regulation of interferon-gamma-mediated signaling pathway
  • positive regulation of PERK-mediated unfolded protein response
  • positive regulation of gluconeogenesis
  • erythrocyte differentiation
  • B cell differentiation
  • negative regulation of interferon-gamma-mediated signaling pathway
  • negative regulation of ERK1 and ERK2 cascade
  • negative regulation of tumor necrosis factor-mediated signaling pathway
  • regulation of hepatocyte growth factor receptor signaling pathway
  • negative regulation of insulin receptor signaling pathway
  • peptidyl-tyrosine dephosphorylation
  • glucose homeostasis
  • negative regulation of platelet-derived growth factor receptor-beta signaling pathway
  • negative regulation of interleukin-2-mediated signaling pathway
  • negative regulation of macrophage differentiation
  • negative regulation of interleukin-4-mediated signaling pathway
  • negative regulation of epidermal growth factor receptor signaling pathway
  • insulin receptor signaling pathway
  • negative regulation of macrophage colony-stimulating factor signaling pathway
  • negative regulation of lipid storage
  • negative regulation of cell proliferation
  • negative regulation of positive thymic T cell selection
  • negative regulation of tyrosine phosphorylation of Stat3 protein
  • negative regulation of inflammatory response
  • negative regulation of prolactin signaling pathway
Components
  • endoplasmic reticulum-Golgi intermediate compartment
  • nucleus
  • endoplasmic reticulum
  • plasma membrane
  • nucleoplasm
General FunctionSyntaxin binding
Specific FunctionNon-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3, STAT5A, STAT5B and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the development of the immune system. Functions in T-cell receptor signaling through dephosphorylation of FYN and LCK to control T-cells differentiation and activation. Dephosphorylates CSF1R, negatively regulating its downstream signaling and macrophage differentiation. Negatively regulates cytokine (IL2/interleukin-2 and interferon)-mediated signaling through dephosphorylation of the cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that propagate signaling downstream of the cytokine receptors. Also regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine signaling through dephosphorylation of STAT3 and STAT6 respectively. In addition to the immune system, it is involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth. Activated by the integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates EGF signaling. Dephosphorylates PDGFRB and negatively regulates platelet-derived growth factor receptor-beta signaling pathway and therefore cell proliferation. Negatively regulates tumor necrosis factor-mediated signaling downstream via MAPK through SRC dephosphorylation. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of the hepatocyte growth factor receptor MET. Plays also an important role in glucose homeostasis. For instance, negatively regulates the insulin receptor signaling pathway through the dephosphorylation of INSR and control gluconeogenesis and liver glucose production through negative regulation of the IL6 signaling pathways. Finally, it negatively regulates prolactin-mediated signaling pathway through dephosphorylation of STAT5A and STAT5B. May also bind DNA.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP17706
UniProtKB Entry NamePTN2_HUMAN
Cellular LocationEndoplasmic reticulum
Gene sequence
>lcl|BSEQ0020842|Tyrosine-protein phosphatase non-receptor type 2 (PTPN2)
ATGCCCACCACCATCGAGCGGGAGTTCGAAGAGTTGGATACTCAGCGTCGCTGGCAGCCG
CTGTACTTGGAAATTCGAAATGAGTCCCATGACTATCCTCATAGAGTGGCCAAGTTTCCA
GAAAACAGAAATCGAAACAGATACAGAGATGTAAGCCCATATGATCACAGTCGTGTTAAA
CTGCAAAATGCTGAGAATGATTATATTAATGCCAGTTTAGTTGACATAGAAGAGGCACAA
AGGAGTTACATCTTAACACAGGGTCCACTTCCTAACACATGCTGCCATTTCTGGCTTATG
GTTTGGCAGCAGAAGACCAAAGCAGTTGTCATGCTGAACCGCATTGTGGAGAAAGAATCG
GTTAAATGTGCACAGTACTGGCCAACAGATGACCAAGAGATGCTGTTTAAAGAAACAGGA
TTCAGTGTGAAGCTCTTGTCAGAAGATGTGAAGTCGTATTATACAGTACATCTACTACAA
TTAGAAAATATCAATTATATTGAGAACTTGTGGATCACACTGTATTTGAAATTATTAATG
CTGGATGTTAAAAGGTCACTAAAAAGTGGTGAAACCAGAACAATATCTCACTTTCATTAT
ACTACCTGGCCAGATTTTGGAGTCCCTGAATCACCAGCTTCATTTCTCAATTTCTTGTTT
AAAGTGAGAGAATCTGGCTCCTTGAACCCTGACCATGGGCCTGCGGTGATCCACTGTAGT
GCAGGCATTGGGCGCTCTGGCACCTTCTCTCTGGTAGACACTTGTCTTGTTTTGATGGAA
AAAGGAGATGATATTAACATAAAACAAGTGTTACTGAACATGAGAAAATACCGAATGGGT
CTTATTCAGACCCCAGATCAACTGAGATTCTCATACATGGCTATAATAGAAGGAGCAAAA
TGTATAAAGGGAGATTCTAGTATACAGAAACGATGGAAAGAACTTTCTAAGGAAGACTTA
TCTCCTGCCTTTGATCATTCACCAAACAAAATAATGACTGAAAAATACAATGGGAACAGA
ATAGGTCTAGAAGAAGAAAAACTGACAGGTGACCGATGTACAGGACTTTCCTCTAAAATG
CAAGATACAATGGAGGAGAACAGTGAGAGTGCTCTACGGAAACGTATTCGAGAGGACAGA
AAGGCCACCACAGCTCAGAAGGTGCAGCAGATGAAACAGAGGCTAAATGAGAATGAACGA
AAAAGAAAAAGGCCAAGATTGACAGACACCTAA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:9650
Chromosome Location18
LocusNot Available
References
  1. Cool DE, Tonks NK, Charbonneau H, Walsh KA, Fischer EH, Krebs EG: cDNA isolated from a human T-cell library encodes a member of the protein-tyrosine-phosphatase family. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5257-61. 2546150
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  3. Nusbaum C, Zody MC, Borowsky ML, Kamal M, Kodira CD, Taylor TD, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Abouelleil A, Allen NR, Anderson S, Bloom T, Bugalter B, Butler J, Cook A, DeCaprio D, Engels R, Garber M, Gnirke A, Hafez N, Hall JL, Norman CH, Itoh T, Jaffe DB, Kuroki Y, Lehoczky J, Lui A, Macdonald P, Mauceli E, Mikkelsen TS, Naylor JW, Nicol R, Nguyen C, Noguchi H, O'Leary SB, O'Neill K, Piqani B, Smith CL, Talamas JA, Topham K, Totoki Y, Toyoda A, Wain HM, Young SK, Zeng Q, Zimmer AR, Fujiyama A, Hattori M, Birren BW, Sakaki Y, Lander ES: DNA sequence and analysis of human chromosome 18. Nature. 2005 Sep 22;437(7058):551-5. 16177791
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  5. Mosinger B Jr, 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. 1992 Jan 15;89(2):499-503. 1731319
  6. 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. 1995 Nov;131(3):631-43. 7593185
  7. Hao L, Tiganis T, Tonks NK, Charbonneau H: The noncatalytic C-terminal segment of the T cell protein tyrosine phosphatase regulates activity via an intramolecular mechanism. J Biol Chem. 1997 Nov 14;272(46):29322-9. 9361013
  8. 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. 1998 Mar;18(3):1622-34. 9488479
  9. Walchli S, Curchod ML, Gobert RP, Arkinstall S, Hooft van Huijsduijnen R: Identification of tyrosine phosphatases that dephosphorylate the insulin receptor. A brute force approach based on "substrate-trapping" mutants. J Biol Chem. 2000 Mar 31;275(13):9792-6. 10734133
  10. Yamamoto T, Sekine Y, Kashima K, Kubota A, Sato N, Aoki N, Matsuda T: The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation. Biochem Biophys Res Commun. 2002 Oct 4;297(4):811-7. 12359225
  11. Simoncic PD, Lee-Loy A, Barber DL, Tremblay ML, McGlade CJ: The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3. Curr Biol. 2002 Mar 19;12(6):446-53. 11909529
  12. ten Hoeve J, de Jesus Ibarra-Sanchez M, Fu Y, Zhu W, Tremblay M, David M, Shuai K: Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol. 2002 Aug;22(16):5662-8. 12138178
  13. Galic S, Klingler-Hoffmann M, Fodero-Tavoletti MT, Puryer MA, Meng TC, Tonks NK, Tiganis T: Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP. Mol Cell Biol. 2003 Mar;23(6):2096-108. 12612081
  14. Bukczynska P, Klingler-Hoffmann M, Mitchelhill KI, Lam MH, Ciccomancini M, Tonks NK, Sarcevic B, Kemp BE, Tiganis T: The T-cell protein tyrosine phosphatase is phosphorylated on Ser-304 by cyclin-dependent protein kinases in mitosis. Biochem J. 2004 Jun 15;380(Pt 3):939-49. 15030318
  15. Persson C, Savenhed C, Bourdeau A, Tremblay ML, Markova B, Bohmer FD, Haj FG, Neel BG, Elson A, Heldin CH, Ronnstrand L, Ostman A, Hellberg C: Site-selective regulation of platelet-derived growth factor beta receptor tyrosine phosphorylation by T-cell protein tyrosine phosphatase. Mol Cell Biol. 2004 Mar;24(5):2190-201. 14966296
  16. Stenzinger A, Kajosch T, Tag C, Porsche A, Welte I, Hofer HW, Steger K, Wimmer M: The novel protein PTPIP51 exhibits tissue- and cell-specific expression. Histochem Cell Biol. 2005 Jan;123(1):19-28. Epub 2004 Dec 18. 15609043
  17. Mattila E, Pellinen T, Nevo J, Vuoriluoto K, Arjonen A, Ivaska J: Negative regulation of EGFR signalling through integrin-alpha1beta1-mediated activation of protein tyrosine phosphatase TCPTP. Nat Cell Biol. 2005 Jan;7(1):78-85. Epub 2004 Dec 12. 15592458
  18. van Vliet C, Bukczynska PE, Puryer MA, Sadek CM, Shields BJ, Tremblay ML, Tiganis T: Selective regulation of tumor necrosis factor-induced Erk signaling by Src family kinases and the T cell protein tyrosine phosphatase. Nat Immunol. 2005 Mar;6(3):253-60. Epub 2005 Feb 6. 15696169
  19. Wang S, Raven JF, Baltzis D, Kazemi S, Brunet DV, Hatzoglou M, Tremblay ML, Koromilas AE: The catalytic activity of the eukaryotic initiation factor-2alpha kinase PKR is required to negatively regulate Stat1 and Stat3 via activation of the T-cell protein-tyrosine phosphatase. J Biol Chem. 2006 Apr 7;281(14):9439-49. Epub 2006 Jan 23. 16431927
  20. Gupta V, Swarup G: Evidence for a role of transmembrane protein p25 in localization of protein tyrosine phosphatase TC48 to the ER. J Cell Sci. 2006 May 1;119(Pt 9):1703-14. Epub 2006 Apr 4. 16595549
  21. Lu X, Chen J, Sasmono RT, Hsi ED, Sarosiek KA, Tiganis T, Lossos IS: T-cell protein tyrosine phosphatase, distinctively expressed in activated-B-cell-like diffuse large B-cell lymphomas, is the nuclear phosphatase of STAT6. Mol Cell Biol. 2007 Mar;27(6):2166-79. Epub 2007 Jan 8. 17210636
  22. Sangwan V, Paliouras GN, Abella JV, Dube N, Monast A, Tremblay ML, Park M: Regulation of the Met receptor-tyrosine kinase by the protein-tyrosine phosphatase 1B and T-cell phosphatase. J Biol Chem. 2008 Dec 5;283(49):34374-83. doi: 10.1074/jbc.M805916200. Epub 2008 Sep 26. 18819921
  23. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  24. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  25. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  26. Wiede F, Shields BJ, Chew SH, Kyparissoudis K, van Vliet C, Galic S, Tremblay ML, Russell SM, Godfrey DI, Tiganis T: T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice. J Clin Invest. 2011 Dec;121(12):4758-74. doi: 10.1172/JCI59492. Epub 2011 Nov 14. 22080863
  27. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
  28. Muppirala M, Gupta V, Swarup G: Tyrosine phosphorylation of a SNARE protein, syntaxin 17: implications for membrane trafficking in the early secretory pathway. Biochim Biophys Acta. 2012 Dec;1823(12):2109-19. doi: 10.1016/j.bbamcr.2012.09.003. Epub 2012 Sep 21. 23006999
  29. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  30. Iversen LF, Moller KB, Pedersen AK, Peters GH, Petersen AS, Andersen HS, Branner S, Mortensen SB, Moller NP: Structure determination of T cell protein-tyrosine phosphatase. J Biol Chem. 2002 May 31;277(22):19982-90. Epub 2002 Mar 20. 11907034