Tyrosine-protein phosphatase non-receptor type 6

NameTyrosine-protein phosphatase non-receptor type 6
Synonyms
  • 3.1.3.48
  • HCP
  • Hematopoietic cell protein-tyrosine phosphatase
  • Protein-tyrosine phosphatase 1C
  • Protein-tyrosine phosphatase SHP-1
  • PTP-1C
  • PTP1C
  • SH-PTP1
Gene NamePTPN6
OrganismHuman
Amino acid sequence
>lcl|BSEQ0008997|Tyrosine-protein phosphatase non-receptor type 6
MVRWFHRDLSGLDAETLLKGRGVHGSFLARPSRKNQGDFSLSVRVGDQVTHIRIQNSGDF
YDLYGGEKFATLTELVEYYTQQQGVLQDRDGTIIHLKYPLNCSDPTSERWYHGHMSGGQA
ETLLQAKGEPWTFLVRESLSQPGDFVLSVLSDQPKAGPGSPLRVTHIKVMCEGGRYTVGG
LETFDSLTDLVEHFKKTGIEEASGAFVYLRQPYYATRVNAADIENRVLELNKKQESEDTA
KAGFWEEFESLQKQEVKNLHQRLEGQRPENKGKNRYKNILPFDHSRVILQGRDSNIPGSD
YINANYIKNQLLGPDENAKTYIASQGCLEATVNDFWQMAWQENSRVIVMTTREVEKGRNK
CVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGDLIREIWHYQYLSWPDH
GVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMENISTKGLDC
DIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEVLQSQKGQESEYGNIT
YPPAMKNAHAKASRTSSKHKEDVYENLHTKNKREEKVKKQRSADKEKSKGSLKRK
Number of residues595
Molecular Weight67560.79
Theoretical pINot Available
GO Classification
Functions
  • protein kinase binding
  • protein tyrosine phosphatase activity
  • transmembrane receptor protein tyrosine phosphatase activity
Processes
  • blood coagulation
  • T cell costimulation
  • protein dephosphorylation
  • JAK-STAT cascade involved in growth hormone signaling pathway
  • cell proliferation
  • regulation of type I interferon-mediated signaling pathway
  • type I interferon signaling pathway
  • interferon-gamma-mediated signaling pathway
  • regulation of interferon-gamma-mediated signaling pathway
  • cell differentiation
  • regulation of ERK1 and ERK2 cascade
  • peptidyl-tyrosine phosphorylation
  • peptidyl-tyrosine dephosphorylation
  • leukocyte migration
  • negative regulation of peptidyl-tyrosine phosphorylation
  • apoptotic process
  • negative regulation of cell proliferation
  • regulation of G1/S transition of mitotic cell cycle
  • G-protein coupled receptor signaling pathway
  • positive regulation of cell proliferation
  • positive regulation of phosphatidylinositol 3-kinase signaling
  • cytokine-mediated signaling pathway
Components
  • nucleus
  • cytosol
  • extracellular exosome
  • nucleolus
  • cytoplasm
  • membrane
General FunctionTransmembrane receptor protein tyrosine phosphatase activity
Specific FunctionModulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP29350
UniProtKB Entry NamePTN6_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0013555|Tyrosine-protein phosphatase non-receptor type 6 (PTPN6)
ATGGTGAGGTGGTTTCACCGAGACCTCAGTGGGCTGGATGCAGAGACCCTGCTCAAGGGC
CGAGGTGTCCACGGTAGCTTCCTGGCTCGGCCCAGTCGCAAGAACCAGGGTGACTTCTCG
CTCTCCGTCAGGGTGGGGGATCAGGTGACCCATATTCGGATCCAGAACTCAGGGGATTTC
TATGACCTGTATGGAGGGGAGAAGTTTGCGACTCTGACAGAGCTGGTGGAGTACTACACT
CAGCAGCAGGGTGTCCTGCAGGACCGCGACGGCACCATCATCCACCTCAAGTACCCGCTG
AACTGCTCCGATCCCACTAGTGAGAGGTGGTACCATGGCCACATGTCTGGCGGGCAGGCA
GAGACGCTGCTGCAGGCCAAGGGCGAGCCCTGGACGTTTCTTGTGCGTGAGAGCCTCAGC
CAGCCTGGAGACTTCGTGCTTTCTGTGCTCAGTGACCAGCCCAAGGCTGGCCCAGGCTCC
CCGCTCAGGGTCACCCACATCAAGGTCATGTGCGAGGGTGGACGCTACACAGTGGGTGGT
TTGGAGACCTTCGACAGCCTCACGGACCTGGTGGAGCATTTCAAGAAGACGGGGATTGAG
GAGGCCTCAGGCGCCTTTGTCTACCTGCGGCAGCCGTACTATGCCACGAGGGTGAATGCG
GCTGACATTGAGAACCGAGTGTTGGAACTGAACAAGAAGCAGGAGTCCGAGGATACAGCC
AAGGCTGGCTTCTGGGAGGAGTTTGAGAGTTTGCAGAAGCAGGAGGTGAAGAACTTGCAC
CAGCGTCTGGAAGGGCAGCGGCCAGAGAACAAGGGCAAGAACCGCTACAAGAACATTCTC
CCCTTTGACCACAGCCGAGTGATCCTGCAGGGACGGGACAGTAACATCCCCGGGTCCGAC
TACATCAATGCCAACTACATCAAGAACCAGCTGCTAGGCCCTGATGAGAACGCTAAGACC
TACATCGCCAGCCAGGGCTGTCTGGAGGCCACGGTCAATGACTTCTGGCAGATGGCGTGG
CAGGAGAACAGCCGTGTCATCGTCATGACCACCCGAGAGGTGGAGAAAGGCCGGAACAAA
TGCGTCCCATACTGGCCCGAGGTGGGCATGCAGCGTGCTTATGGGCCCTACTCTGTGACC
AACTGCGGGGAGCATGACACAACCGAATACAAACTCCGTACCTTACAGGTCTCCCCGCTG
GACAATGGAGACCTGATTCGGGAGATCTGGCATTACCAGTACCTGAGCTGGCCCGACCAT
GGGGTCCCCAGTGAGCCTGGGGGTGTCCTCAGCTTCCTGGACCAGATCAACCAGCGGCAG
GAAAGTCTGCCTCACGCAGGGCCCATCATCGTGCACTGCAGCGCCGGCATCGGCCGCACA
GGCACCATCATTGTCATCGACATGCTCATGGAGAACATCTCCACCAAGGGCCTGGACTGT
GACATTGACATCCAGAAGACCATCCAGATGGTGCGGGCGCAGCGCTCGGGCATGGTGCAG
ACGGAGGCGCAGTACAAGTTCATCTACGTGGCCATCGCCCAGTTCATTGAAACCACTAAG
AAGAAGCTGGAGGTCCTGCAGTCGCAGAAGGGCCAGGAGTCGGAGTACGGGAACATCACC
TATCCCCCAGCCATGAAGAATGCCCATGCCAAGGCCTCCCGCACCTCGTCCAAACACAAG
GAGGATGTGTATGAGAACCTGCACACTAAGAACAAGAGGGAGGAGAAAGTGAAGAAGCAG
CGGTCAGCAGACAAGGAGAAGAGCAAGGGTTCCCTCAAGAGGAAGTGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:9658
Chromosome Location12
LocusNot Available
References
  1. Yi TL, Cleveland JL, Ihle JN: Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13. Mol Cell Biol. 1992 Feb;12(2):836-46. 1732748
  2. Shen SH, Bastien L, Posner BI, Chretien P: A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases. Nature. 1991 Aug 22;352(6337):736-9. 1652101
  3. Plutzky J, Neel BG, Rosenberg RD: Isolation of a src homology 2-containing tyrosine phosphatase. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1123-7. 1736296
  4. Banville D, Stocco R, Shen SH: Human protein tyrosine phosphatase 1C (PTPN6) gene structure: alternate promoter usage and exon skipping generate multiple transcripts. Genomics. 1995 May 1;27(1):165-73. 7665165
  5. Ansari-Lari MA, Shen Y, Muzny DM, Lee W, Gibbs RA: Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination. Genome Res. 1997 Mar;7(3):268-80. 9074930
  6. Jin YJ, Yu CL, Burakoff SJ: Human 70-kDa SHP-1L differs from 68-kDa SHP-1 in its C-terminal structure and catalytic activity. J Biol Chem. 1999 Oct 1;274(40):28301-7. 10497187
  7. 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
  8. Scherer SE, Muzny DM, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Montgomery KT, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Lovering RC, Wheeler DA, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Draper H, Gonzalez-Garay ML, Havlak P, Jackson LR, Jacob LS, Kelly SH, Li L, Li Z, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Pasternak S, Perez LM, Plopper FJ, Santibanez J, Shen H, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Zhang J, Zhou J, Allen CC, Amin AG, Anyalebechi V, Bailey M, Barbaria JA, Bimage KE, Bryant NP, Burch PE, Burkett CE, Burrell KL, Calderon E, Cardenas V, Carter K, Casias K, Cavazos I, Cavazos SR, Ceasar H, Chacko J, Chan SN, Chavez D, Christopoulos C, Chu J, Cockrell R, Cox CD, Dang M, Dathorne SR, David R, Davis CM, Davy-Carroll L, Deshazo DR, Donlin JE, D'Souza L, Eaves KA, Egan A, Emery-Cohen AJ, Escotto M, Flagg N, Forbes LD, Gabisi AM, Garza M, Hamilton C, Henderson N, Hernandez O, Hines S, Hogues ME, Huang M, Idlebird DG, Johnson R, Jolivet A, Jones S, Kagan R, King LM, Leal B, Lebow H, Lee S, LeVan JM, Lewis LC, London P, Lorensuhewa LM, Loulseged H, Lovett DA, Lucier A, Lucier RL, Ma J, Madu RC, Mapua P, Martindale AD, Martinez E, Massey E, Mawhiney S, Meador MG, Mendez S, Mercado C, Mercado IC, Merritt CE, Miner ZL, Minja E, Mitchell T, Mohabbat F, Mohabbat K, Montgomery B, Moore N, Morris S, Munidasa M, Ngo RN, Nguyen NB, Nickerson E, Nwaokelemeh OO, Nwokenkwo S, Obregon M, Oguh M, Oragunye N, Oviedo RJ, Parish BJ, Parker DN, Parrish J, Parks KL, Paul HA, Payton BA, Perez A, Perrin W, Pickens A, Primus EL, Pu LL, Puazo M, Quiles MM, Quiroz JB, Rabata D, Reeves K, Ruiz SJ, Shao H, Sisson I, Sonaike T, Sorelle RP, Sutton AE, Svatek AF, Svetz LA, Tamerisa KS, Taylor TR, Teague B, Thomas N, Thorn RD, Trejos ZY, Trevino BK, Ukegbu ON, Urban JB, Vasquez LI, Vera VA, Villasana DM, Wang L, Ward-Moore S, Warren JT, Wei X, White F, Williamson AL, Wleczyk R, Wooden HS, Wooden SH, Yen J, Yoon L, Yoon V, Zorrilla SE, Nelson D, Kucherlapati R, Weinstock G, Gibbs RA: The finished DNA sequence of human chromosome 12. Nature. 2006 Mar 16;440(7082):346-51. 16541075
  9. 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
  10. Li RY, Gaits F, Ragab A, Ragab-Thomas JM, Chap H: Tyrosine phosphorylation of an SH2-containing protein tyrosine phosphatase is coupled to platelet thrombin receptor via a pertussis toxin-sensitive heterotrimeric G-protein. EMBO J. 1995 Jun 1;14(11):2519-26. 7781604
  11. Cosman D, Fanger N, Borges L, Kubin M, Chin W, Peterson L, Hsu ML: A novel immunoglobulin superfamily receptor for cellular and viral MHC class I molecules. Immunity. 1997 Aug;7(2):273-82. 9285411
  12. Fanger NA, Cosman D, Peterson L, Braddy SC, Maliszewski CR, Borges L: The MHC class I binding proteins LIR-1 and LIR-2 inhibit Fc receptor-mediated signaling in monocytes. Eur J Immunol. 1998 Nov;28(11):3423-34. 9842885
  13. Veillette A, Thibaudeau E, Latour S: High expression of inhibitory receptor SHPS-1 and its association with protein-tyrosine phosphatase SHP-1 in macrophages. J Biol Chem. 1998 Aug 28;273(35):22719-28. 9712903
  14. Yoshida K, Kharbanda S, Kufe D: Functional interaction between SHPTP1 and the Lyn tyrosine kinase in the apoptotic response to DNA damage. J Biol Chem. 1999 Dec 3;274(49):34663-8. 10574931
  15. Xu MJ, Zhao R, Zhao ZJ: Molecular cloning and characterization of SPAP1, an inhibitory receptor. Biochem Biophys Res Commun. 2001 Jan 26;280(3):768-75. 11162587
  16. Lewis J, Eiben LJ, Nelson DL, Cohen JI, Nichols KE, Ochs HD, Notarangelo LD, Duckett CS: Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family. Clin Immunol. 2001 Jul;100(1):15-23. 11414741
  17. Keilhack H, Muller M, Bohmer SA, Frank C, Weidner KM, Birchmeier W, Ligensa T, Berndt A, Kosmehl H, Gunther B, Muller T, Birchmeier C, Bohmer FD: Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1. J Cell Biol. 2001 Jan 22;152(2):325-34. 11266449
  18. Ehrhardt GR, Davis RS, Hsu JT, Leu CM, Ehrhardt A, Cooper MD: The inhibitory potential of Fc receptor homolog 4 on memory B cells. Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13489-94. Epub 2003 Nov 3. 14597715
  19. Sui L, Li N, Liu Q, Zhang W, Wan T, Wang B, Luo K, Sun H, Cao X: IgSF13, a novel human inhibitory receptor of the immunoglobulin superfamily, is preferentially expressed in dendritic cells and monocytes. Biochem Biophys Res Commun. 2004 Jul 2;319(3):920-8. 15184070
  20. Ronnstrand L: Signal transduction via the stem cell factor receptor/c-Kit. Cell Mol Life Sci. 2004 Oct;61(19-20):2535-48. 15526160
  21. Roskoski R Jr: Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor. Biochem Biophys Res Commun. 2005 Nov 11;337(1):1-13. 16129412
  22. Yu MC, Su LL, Zou L, Liu Y, Wu N, Kong L, Zhuang ZH, Sun L, Liu HP, Hu JH, Li D, Strominger JL, Zang JW, Pei G, Ge BX: An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells. Nat Immunol. 2008 Aug;9(8):898-907. doi: 10.1038/ni.1635. Epub 2008 Jul 11. 18604210
  23. Sephton CF, Zhang D, Lehmann TM, Pennington PR, Scheid MP, Mousseau DD: The nuclear localization of 3'-phosphoinositide-dependent kinase-1 is dependent on its association with the protein tyrosine phosphatase SHP-1. Cell Signal. 2009 Nov;21(11):1634-44. doi: 10.1016/j.cellsig.2009.06.010. Epub 2009 Jul 8. 19591923
  24. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  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. Fiset A, Xu E, Bergeron S, Marette A, Pelletier G, Siminovitch KA, Olivier M, Beauchemin N, Faure RL: Compartmentalized CDK2 is connected with SHP-1 and beta-catenin and regulates insulin internalization. Cell Signal. 2011 May;23(5):911-9. doi: 10.1016/j.cellsig.2011.01.019. Epub 2011 Jan 22. 21262353
  27. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  28. Yang J, Liang X, Niu T, Meng W, Zhao Z, Zhou GW: Crystal structure of the catalytic domain of protein-tyrosine phosphatase SHP-1. J Biol Chem. 1998 Oct 23;273(43):28199-207. 9774441
  29. Yang J, Liu L, He D, Song X, Liang X, Zhao ZJ, Zhou GW: Crystal structure of human protein-tyrosine phosphatase SHP-1. J Biol Chem. 2003 Feb 21;278(8):6516-20. Epub 2002 Dec 13. 12482860
  30. Wang W, Liu L, Song X, Mo Y, Komma C, Bellamy HD, Zhao ZJ, Zhou GW: Crystal structure of human protein tyrosine phosphatase SHP-1 in the open conformation. J Cell Biochem. 2011 Aug;112(8):2062-71. doi: 10.1002/jcb.23125. 21465528