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Identification
HMDB Protein ID HMDBP08931
Secondary Accession Numbers
  • 14660
Name Tyrosine-protein phosphatase non-receptor type 1
Synonyms
  1. PTP-1B
  2. Protein-tyrosine phosphatase 1B
Gene Name PTPN1
Protein Type Enzyme
Biological Properties
General Function Involved in phosphatase activity
Specific Function Tyrosine-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.
Pathways
  • Adherens junction
  • Insulin signaling pathway
Reactions
Protein tyrosine phosphate + Water → protein tyrosine + Phosphoric acid details
GO Classification
Biological Process
platelet activation
negative regulation of insulin receptor signaling pathway
interferon-gamma-mediated signaling pathway
insulin receptor signaling pathway
endoplasmic reticulum unfolded protein response
regulation of interferon-gamma-mediated signaling pathway
regulation of type I interferon-mediated signaling pathway
type I interferon-mediated signaling pathway
JAK-STAT cascade involved in growth hormone signaling pathway
regulation of endocytosis
actin cytoskeleton reorganization
Cellular Component
endoplasmic reticulum membrane
cytosol
endoplasmic reticulum
early endosome
cytoplasmic vesicle
Function
phosphoprotein phosphatase activity
protein tyrosine phosphatase activity
hydrolase activity, acting on ester bonds
catalytic activity
hydrolase activity
phosphoric ester hydrolase activity
phosphatase activity
Molecular Function
zinc ion binding
protein tyrosine phosphatase activity
Process
phosphorus metabolic process
phosphate metabolic process
dephosphorylation
protein amino acid dephosphorylation
metabolic process
cellular metabolic process
Cellular Location
  1. Peripheral membrane protein
  2. Endoplasmic reticulum membrane
  3. Cytoplasmic side
Gene Properties
Chromosome Location 20
Locus 20q13.1-q13.2
SNPs PTPN1
Gene Sequence
>1308 bp
ATGGAGATGGAAAAGGAGTTCGAGCAGATCGACAAGTCCGGGAGCTGGGCGGCCATTTAC
CAGGATATCCGACATGAAGCCAGTGACTTCCCATGTAGAGTGGCCAAGCTTCCTAAGAAC
AAAAACCGAAATAGGTACAGAGACGTCAGTCCCTTTGACCATAGTCGGATTAAACTACAT
CAAGAAGATAATGACTATATCAACGCTAGTTTGATAAAAATGGAAGAAGCCCAAAGGAGT
TACATTCTTACCCAGGGCCCTTTGCCTAACACATGCGGTCACTTTTGGGAGATGGTGTGG
GAGCAGAAAAGCAGGGGTGTCGTCATGCTCAACAGAGTGATGGAGAAAGGTTCGTTAAAA
TGCGCACAATACTGGCCACAAAAAGAAGAAAAAGAGATGATCTTTGAAGACACAAATTTG
AAATTAACATTGATCTCTGAAGATATCAAGTCATATTATACAGTGCGACAGCTAGAATTG
GAAAACCTTACAACCCAAGAAACTCGAGAGATCTTACATTTCCACTATACCACATGGCCT
GACTTTGGAGTCCCTGAATCACCAGCCTCATTCTTGAACTTTCTTTTCAAAGTCCGAGAG
TCAGGGTCACTCAGCCCGGAGCACGGGCCCGTTGTGGTGCACTGCAGTGCAGGCATCGGC
AGGTCTGGAACCTTCTGTCTGGCTGATACCTGCCTCCTGCTGATGGACAAGAGGAAAGAC
CCTTCTTCCGTTGATATCAAGAAAGTGCTGTTAGAAATGAGGAAGTTTCGGATGGGGTTG
ATCCAGACAGCCGACCAGCTGCGCTTCTCCTACCTGGCTGTGATCGAAGGTGCCAAATTC
ATCATGGGGGACTCTTCCGTGCAGGATCAGTGGAAGGAGCTTTCCCACGAGGACCTGGAG
CCCCCACCCGAGCATATCCCCCCACCTCCCCGGCCACCCAAACGAATCCTGGAGCCACAC
AATGGGAAATGCAGGGAGTTCTTCCCAAATCACCAGTGGGTGAAGGAAGAGACCCAGGAG
GATAAAGACTGCCCCATCAAGGAAGAAAAAGGAAGCCCCTTAAATGCCGCACCCTACGGC
ATCGAAAGCATGAGTCAAGACACTGAAGTTAGAAGTCGGGTCGTGGGGGGAAGTCTTCGA
GGTGCCCAGGCTGCCTCCCCAGCCAAAGGGGAGCCGTCACTGCCCGAGAAGGACGAGGAC
CATGCACTGAGTTACTGGAAGCCCTTCCTGGTCAACATGTGCGTGGCTACGGTCCTCACG
GCCGGCGCTTACCTCTGCTACAGGTTCCTGTTCAACAGCAACACATAG
Protein Properties
Number of Residues 435
Molecular Weight 49966.44
Theoretical pI 6.264
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Tyrosine-protein phosphatase non-receptor type 1
MEMEKEFEQIDKSGSWAAIYQDIRHEASDFPCRVAKLPKNKNRNRYRDVSPFDHSRIKLH
QEDNDYINASLIKMEEAQRSYILTQGPLPNTCGHFWEMVWEQKSRGVVMLNRVMEKGSLK
CAQYWPQKEEKEMIFEDTNLKLTLISEDIKSYYTVRQLELENLTTQETREILHFHYTTWP
DFGVPESPASFLNFLFKVRESGSLSPEHGPVVVHCSAGIGRSGTFCLADTCLLLMDKRKD
PSSVDIKKVLLEMRKFRMGLIQTADQLRFSYLAVIEGAKFIMGDSSVQDQWKELSHEDLE
PPPEHIPPPPRPPKRILEPHNGKCREFFPNHQWVKEETQEDKDCPIKEEKGSPLNAAPYG
IESMSQDTEVRSRVVGGSLRGAQAASPAKGEPSLPEKDEDHALSYWKPFLVNMCVATVLT
AGAYLCYRFLFNSNT
GenBank ID Protein 190742
UniProtKB/Swiss-Prot ID P18031
UniProtKB/Swiss-Prot Entry Name PTN1_HUMAN
PDB IDs
GenBank Gene ID M31724
GeneCard ID PTPN1
GenAtlas ID PTPN1
HGNC ID HGNC:9642
References
General References
  1. 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 ]
  2. 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. [PubMed:15592455 ]
  3. 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. [PubMed:18691976 ]
  4. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  5. 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. [PubMed:11780052 ]
  6. 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. [PubMed:2157211 ]
  7. 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. [PubMed:2164224 ]
  8. 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. [PubMed:2546149 ]
  9. 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. [PubMed:8491187 ]
  10. 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. [PubMed:1739967 ]
  11. 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. [PubMed:11579209 ]
  12. Barford D, Flint AJ, Tonks NK: Crystal structure of human protein tyrosine phosphatase 1B. Science. 1994 Mar 11;263(5152):1397-404. [PubMed:8128219 ]
  13. 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. [PubMed:9391040 ]
  14. 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. [PubMed:9553104 ]
  15. 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. [PubMed:9922143 ]
  16. 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. [PubMed:12802338 ]
  17. 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. [PubMed:12802339 ]
  18. 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. [PubMed:15919835 ]