Tyrosine-protein phosphatase non-receptor type 1

NameTyrosine-protein phosphatase non-receptor type 1
Synonyms
  • 3.1.3.48
  • Protein-tyrosine phosphatase 1B
  • PTP-1B
  • PTP1B
Gene NamePTPN1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0018983|Tyrosine-protein phosphatase non-receptor type 1
MEMEKEFEQIDKSGSWAAIYQDIRHEASDFPCRVAKLPKNKNRNRYRDVSPFDHSRIKLH
QEDNDYINASLIKMEEAQRSYILTQGPLPNTCGHFWEMVWEQKSRGVVMLNRVMEKGSLK
CAQYWPQKEEKEMIFEDTNLKLTLISEDIKSYYTVRQLELENLTTQETREILHFHYTTWP
DFGVPESPASFLNFLFKVRESGSLSPEHGPVVVHCSAGIGRSGTFCLADTCLLLMDKRKD
PSSVDIKKVLLEMRKFRMGLIQTADQLRFSYLAVIEGAKFIMGDSSVQDQWKELSHEDLE
PPPEHIPPPPRPPKRILEPHNGKCREFFPNHQWVKEETQEDKDCPIKEEKGSPLNAAPYG
IESMSQDTEVRSRVVGGSLRGAQAASPAKGEPSLPEKDEDHALSYWKPFLVNMCVATVLT
AGAYLCYRFLFNSNT
Number of residues435
Molecular Weight49966.44
Theoretical pI6.21
GO Classification
Functions
  • protein kinase binding
  • zinc ion binding
  • receptor tyrosine kinase binding
  • poly(A) RNA binding
  • protein tyrosine phosphatase activity
  • enzyme binding
  • ephrin receptor binding
Processes
  • positive regulation of protein tyrosine kinase activity
  • cytokine-mediated signaling pathway
  • negative regulation of insulin receptor signaling pathway
  • peptidyl-tyrosine dephosphorylation
  • endoplasmic reticulum unfolded protein response
  • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
  • protein dephosphorylation
  • blood coagulation
  • JAK-STAT cascade involved in growth hormone signaling pathway
  • negative regulation of vascular endothelial growth factor receptor signaling pathway
  • regulation of type I interferon-mediated signaling pathway
  • type I interferon signaling pathway
  • regulation of signal transduction
  • platelet activation
  • activation of signaling protein activity involved in unfolded protein response
  • actin cytoskeleton reorganization
  • negative regulation of PERK-mediated unfolded protein response
  • interferon-gamma-mediated signaling pathway
  • peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity
  • regulation of interferon-gamma-mediated signaling pathway
  • positive regulation of IRE1-mediated unfolded protein response
  • negative regulation of MAP kinase activity
  • platelet-derived growth factor receptor-beta signaling pathway
  • positive regulation of receptor catabolic process
  • IRE1-mediated unfolded protein response
  • regulation of endocytosis
  • regulation of hepatocyte growth factor receptor signaling pathway
  • negative regulation of ERK1 and ERK2 cascade
  • activation of JUN kinase activity
  • regulation of intracellular protein transport
  • insulin receptor signaling pathway
Components
  • endoplasmic reticulum
  • cytoplasmic side of endoplasmic reticulum membrane
  • sorting endosome
  • early endosome
  • cytoplasmic vesicle
  • cytosol
General FunctionZinc ion binding
Specific FunctionTyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID190742
UniProtKB IDP18031
UniProtKB Entry NamePTN1_HUMAN
Cellular LocationEndoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0018984|Tyrosine-protein phosphatase non-receptor type 1 (PTPN1)
ATGGAAGAAGCCCAAAGGAGTTACATTCTTACCCAGGGCCCTTTGCCTAACACATGCGGT
CACTTTTGGGAGATGGTGTGGGAGCAGAAAAGCAGGGGTGTCGTCATGCTCAACAGAGTG
ATGGAGAAAGGTTCGTTAAAATGCGCACAATACTGGCCACAAAAAGAAGAAAAAGAGATG
ATCTTTGAAGACACAAATTTGAAATTAACATTGATCTCTGAAGATATCAAGTCATATTAT
ACAGTGCGACAGCTAGAATTGGAAAACCTTACAACCCAAGAAACTCGAGAGATCTTACAT
TTCCACTATACCACATGGCCTGACTTTGGAGTCCCTGAATCACCAGCCTCATTCTTGAAC
TTTCTTTTCAAAGTCCGAGAGTCAGGGTCACTCAGCCCGGAGCACGGGCCCGTTGTGGTG
CACTGCAGTGCAGGCATCGGCAGGTCTGGAACCTTCTGTCTGGCTGATACCTGCCTCTTG
CTGATGGACAAGAGGAAAGACCCTTCTTCCGTTGATATCAAGAAAGTGCTGTTAGAAATG
AGGAAGTTTCGGATGGGGCTGATCCAGACAGCCGACCAGCTGCGCTTCTCCTACCTGGCT
GTGATCGAAGGTGCCAAATTCATCATGGGGGACTCTTCCGTGCAGGATCAGTGGAAGGAG
CTTTCCCACGAGGACCTGGAGCCCCCACCCGAGCATATCCCCCCACCTCCCCGGCCACCC
AAACGAATCCTGGAGCCACACAATGGGAAATGCAGGGAGTTCTTCCCAAATCACCAGTGG
GTGAAGGAAGAGACCCAGGAGGATAAAGACTGCCCCATCAAGGAAGAAAAAGGAAGCCCC
TTAAATGCCGCACCCTACGGCATCGAAAGCATGAGTCAAGACACTGAAGTTAGAAGTCGG
GTCGTGGGGGGAAGTCTTCGAGGTGCCCAGGCTGCCTCCCCAGCCAAAGGGGAGCCGTCA
CTGCCCGAGAAGGACGAGGACCATGCACTGAGTTACTGGAAGCCCTTCCTGGTCAACATG
TGCGTGGCTACGGTCCTCACGGCCGGCGCTTACCTCTGCTACAGGTTCCTGTTCAACAGC
AACACATAG
GenBank Gene IDM31724
GeneCard IDNot Available
GenAtlas IDPTPN1
HGNC IDHGNC:9642
Chromosome Location20
Locus20q13.1-q13.2
References
  1. Chernoff J, Schievella AR, Jost CA, Erikson RL, Neel BG: Cloning of a cDNA for a major human protein-tyrosine-phosphatase. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2735-9. 2157211
  2. 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. 1990 Jul;87(13):5148-52. 2164224
  3. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. 11780052
  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. Charbonneau H, Tonks NK, Kumar S, Diltz CD, Harrylock M, Cool DE, Krebs EG, Fischer EH, Walsh KA: Human placenta protein-tyrosine-phosphatase: amino acid sequence and relationship to a family of receptor-like proteins. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5252-6. 2546149
  6. Flint AJ, Gebbink MF, Franza BR Jr, Hill DE, Tonks NK: Multi-site phosphorylation of the protein tyrosine phosphatase, PTP1B: identification of cell cycle regulated and phorbol ester stimulated sites of phosphorylation. EMBO J. 1993 May;12(5):1937-46. 8491187
  7. Frangioni JV, Beahm PH, Shifrin V, Jost CA, Neel BG: The nontransmembrane tyrosine phosphatase PTP-1B localizes to the endoplasmic reticulum via its 35 amino acid C-terminal sequence. Cell. 1992 Feb 7;68(3):545-60. 1739967
  8. Liu F, Chernoff J: Protein tyrosine phosphatase 1B interacts with and is tyrosine phosphorylated by the epidermal growth factor receptor. Biochem J. 1997 Oct 1;327 ( Pt 1):139-45. 9355745
  9. Moeslein FM, Myers MP, Landreth GE: The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. J Biol Chem. 1999 Sep 17;274(38):26697-704. 10480872
  10. Ravichandran LV, Chen H, Li Y, Quon MJ: Phosphorylation of PTP1B at Ser(50) by Akt impairs its ability to dephosphorylate the insulin receptor. Mol Endocrinol. 2001 Oct;15(10):1768-80. 11579209
  11. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. 15592455
  12. 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
  13. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. 18691976
  14. Nievergall E, Janes PW, Stegmayer C, Vail ME, Haj FG, Teng SW, Neel BG, Bastiaens PI, Lackmann M: PTP1B regulates Eph receptor function and trafficking. J Cell Biol. 2010 Dec 13;191(6):1189-203. doi: 10.1083/jcb.201005035. Epub 2010 Dec 6. 21135139
  15. 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
  16. 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
  17. Krishnan N, Fu C, Pappin DJ, Tonks NK: H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Sci Signal. 2011 Dec 13;4(203):ra86. doi: 10.1126/scisignal.2002329. 22169477
  18. 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
  19. Barford D, Flint AJ, Tonks NK: Crystal structure of human protein tyrosine phosphatase 1B. Science. 1994 Mar 11;263(5152):1397-404. 8128219
  20. Puius YA, Zhao Y, Sullivan M, Lawrence DS, Almo SC, Zhang ZY: Identification of a second aryl phosphate-binding site in protein-tyrosine phosphatase 1B: a paradigm for inhibitor design. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13420-5. 9391040
  21. Pannifer AD, Flint AJ, Tonks NK, Barford D: Visualization of the cysteinyl-phosphate intermediate of a protein-tyrosine phosphatase by x-ray crystallography. J Biol Chem. 1998 Apr 24;273(17):10454-62. 9553104
  22. Groves MR, Yao ZJ, Roller PP, Burke TR Jr, Barford D: Structural basis for inhibition of the protein tyrosine phosphatase 1B by phosphotyrosine peptide mimetics. Biochemistry. 1998 Dec 22;37(51):17773-83. 9922143
  23. Salmeen A, Andersen JN, Myers MP, Meng TC, Hinks JA, Tonks NK, Barford D: Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate. Nature. 2003 Jun 12;423(6941):769-73. 12802338
  24. van Montfort RL, Congreve M, Tisi D, Carr R, Jhoti H: Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B. Nature. 2003 Jun 12;423(6941):773-7. 12802339
  25. Ukkola O, Rankinen T, Lakka T, Leon AS, Skinner JS, Wilmore JH, Rao DC, Kesaniemi YA, Bouchard C: Protein tyrosine phosphatase 1B variant associated with fat distribution and insulin metabolism. Obes Res. 2005 May;13(5):829-34. 15919835