You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP02499
Secondary Accession Numbers
  • 7994
Name Tyrosine-protein phosphatase non-receptor type 6
Synonyms
  1. Hematopoietic cell protein-tyrosine phosphatase
  2. PTP-1C
  3. Protein-tyrosine phosphatase 1C
  4. Protein-tyrosine phosphatase SHP-1
  5. SH-PTP1
Gene Name PTPN6
Protein Type Enzyme
Biological Properties
General Function Involved in phosphatase activity
Specific Function Modulates 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.
Pathways
  • Adherens junction
  • B cell receptor signaling pathway
  • Jak-STAT signaling pathway
  • Leishmaniasis
  • Natural killer cell mediated cytotoxicity
  • Proteoglycans in cancer
  • T cell receptor signaling pathway
Reactions
Protein tyrosine phosphate + Water → protein tyrosine + Phosphoric acid details
GO Classification
Biological Process
apoptotic process
leukocyte migration
positive regulation of cell proliferation
G-protein coupled receptor signaling pathway
cell proliferation
interferon-gamma-mediated signaling pathway
regulation of interferon-gamma-mediated signaling pathway
regulation of type I interferon-mediated signaling pathway
T cell costimulation
type I interferon-mediated signaling pathway
JAK-STAT cascade involved in growth hormone signaling pathway
negative regulation of peptidyl-tyrosine phosphorylation
peptidyl-tyrosine phosphorylation
regulation of ERK1 and ERK2 cascade
blood coagulation
regulation of G1/S transition of mitotic cell cycle
cell differentiation
negative regulation of cell proliferation
positive regulation of phosphatidylinositol 3-kinase cascade
Cellular Component
cytosol
nucleus
membrane
Function
phosphoprotein phosphatase activity
protein tyrosine phosphatase activity
hydrolase activity, acting on ester bonds
binding
catalytic activity
hydrolase activity
phosphoric ester hydrolase activity
phosphatase activity
protein binding
Molecular Function
transmembrane receptor protein tyrosine phosphatase activity
Process
phosphorus metabolic process
phosphate metabolic process
dephosphorylation
protein amino acid dephosphorylation
metabolic process
cellular metabolic process
Cellular Location
  1. Nucleus
  2. Cytoplasm
Gene Properties
Chromosome Location 12
Locus 12p13
SNPs PTPN6
Gene Sequence
>1788 bp
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
Protein Properties
Number of Residues 595
Molecular Weight 67560.79
Theoretical pI 7.784
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Tyrosine-protein phosphatase non-receptor type 6
MVRWFHRDLSGLDAETLLKGRGVHGSFLARPSRKNQGDFSLSVRVGDQVTHIRIQNSGDF
YDLYGGEKFATLTELVEYYTQQQGVLQDRDGTIIHLKYPLNCSDPTSERWYHGHMSGGQA
ETLLQAKGEPWTFLVRESLSQPGDFVLSVLSDQPKAGPGSPLRVTHIKVMCEGGRYTVGG
LETFDSLTDLVEHFKKTGIEEASGAFVYLRQPYYATRVNAADIENRVLELNKKQESEDTA
KAGFWEEFESLQKQEVKNLHQRLEGQRPENKGKNRYKNILPFDHSRVILQGRDSNIPGSD
YINANYIKNQLLGPDENAKTYIASQGCLEATVNDFWQMAWQENSRVIVMTTREVEKGRNK
CVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGDLIREIWHYQYLSWPDH
GVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMENISTKGLDC
DIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEVLQSQKGQESEYGNIT
YPPAMKNAHAKASRTSSKHKEDVYENLHTKNKREEKVKKQRSADKEKSKGSLKRK
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P29350
UniProtKB/Swiss-Prot Entry Name PTN6_HUMAN
PDB IDs
GenBank Gene ID M74903
GeneCard ID PTPN6
GenAtlas ID PTPN6
HGNC ID HGNC:9658
References
General References
  1. 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. [PubMed:14702039 ]
  2. 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. [PubMed:15489334 ]
  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  4. 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. [PubMed:19690332 ]
  5. Imami K, Sugiyama N, Kyono Y, Tomita M, Ishihama Y: Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column. Anal Sci. 2008 Jan;24(1):161-6. [PubMed:18187866 ]
  6. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ: Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203. [PubMed:18083107 ]
  7. Heibeck TH, Ding SJ, Opresko LK, Zhao R, Schepmoes AA, Yang F, Tolmachev AV, Monroe ME, Camp DG 2nd, Smith RD, Wiley HS, Qian WJ: An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells. J Proteome Res. 2009 Aug;8(8):3852-61. doi: 10.1021/pr900044c. [PubMed:19534553 ]
  8. 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. [PubMed:9074930 ]
  9. 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. [PubMed:11162587 ]
  10. 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. [PubMed:1732748 ]
  11. 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. [PubMed:1652101 ]
  12. 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. [PubMed:1736296 ]
  13. 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. [PubMed:7665165 ]
  14. 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. [PubMed:7781604 ]
  15. 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. [PubMed:9285411 ]
  16. 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. [PubMed:9842885 ]
  17. 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. [PubMed:9712903 ]
  18. 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. [PubMed:11414741 ]
  19. 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. [PubMed:14597715 ]
  20. 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. [PubMed:15184070 ]
  21. 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. [PubMed:18604210 ]
  22. 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. [PubMed:9774441 ]