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Identification
HMDB Protein ID HMDBP08933
Secondary Accession Numbers
  • 14662
Name Tyrosine-protein phosphatase non-receptor type 22
Synonyms
  1. Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP
  2. LyP
  3. Lymphoid phosphatase
  4. PEST-domain phosphatase
  5. PEP
Gene Name PTPN22
Protein Type Enzyme
Biological Properties
General Function Involved in phosphatase activity
Specific Function Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules. Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue. Dephosphorylates ZAP70 at its activating 'Tyr-493' residue. Dephosphorylates the immune system activator SKAP2.
Pathways Not Available
Reactions
Protein tyrosine phosphate + Water → protein tyrosine + Phosphate details
GO Classification
Biological Process
phosphoanandamide dephosphorylation
regulation of B cell receptor signaling pathway
regulation of innate immune response
regulation of natural killer cell proliferation
T cell receptor signaling pathway
T cell differentiation
negative regulation of T cell activation
negative regulation of T cell receptor signaling pathway
Cellular Component
perinuclear region of cytoplasm
nucleus
internal side of plasma membrane
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
kinase binding
SH3 domain 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. Cytoplasm
Gene Properties
Chromosome Location 1
Locus 1p13.2
SNPs PTPN22
Gene Sequence
>2424 bp
ATGGACCAAAGAGAAATTCTGCAGAAGTTCCTGGATGAGGCCCAAAGCAAGAAAATTACT
AAAGAGGAGTTTGCCAATGAATTTCTGAAGCTGAAAAGGCAATCTACCAAGTACAAGGCA
GACAAAACCTATCCTACAACTGTGGCTGAGAAGCCCAAGAATATCAAGAAAAACAGATAT
AAGGATATTTTGCCCTATGATTATAGCCGGGTAGAACTATCCCTGATAACCTCTGATGAG
GATTCCAGCTACATCAATGCCAACTTCATTAAGGGAGTTTATGGACCCAAGGCTTATATT
GCCACCCAGGGTCCTTTATCTACAACCCTCCTGGACTTCTGGAGGATGATTTGGGAATAT
AGTGTCCTTATCATTGTTATGGCATGCATGGAGTATGAAATGGGAAAGAAAAAGTGTGAG
CGCTACTGGGCTGAGCCAGGAGAGATGCAGCTGGAATTTGGCCCTTTCTCTGTATCCTGT
GAAGCTGAAAAAAGGAAATCTGATTATATAATCAGGACTCTAAAAGTTAAGTTCAATAGT
GAAACTCGAACTATCTACCAGTTTCATTACAAGAATTGGCCAGACCATGATGTACCTTCA
TCTATAGACCCTATTCTTGAGCTCATCTGGGATGTACGTTGTTACCAAGAGGATGACAGT
GTTCCCATATGCATTCACTGCAGTGCTGGCTGTGGAAGGACTGGTGTTATTTGTGCTATT
GATTATACATGGATGTTGCTAAAAGATGGGATAATTCCTGAGAACTTCAGTGTTTTCAGT
TTGATCCGGGAAATGCGGACACAGAGGCCTTCATTAGTTCAAACGCAGGAACAATATGAA
CTGGTCTACAATGCTGTATTAGAACTATTTAAGAGACAGATGGATGTTATCAGAGATAAA
CATTCTGGAACAGAGAGTCAAGCAAAGCATTGTATTCCTGAGAAAAATCACACTCTCCAA
GCAGACTCTTATTCTCCTAATTTACCAAAAAGTACCACAAAAGCAGCAAAAATGATGAAC
CAACAAAGGACAAAAATGGAAATCAAAGAATCTTCTTCCTTTGACTTTAGGACTTCTGAA
ATAAGTGCAAAAGAAGAGCTAGTTTTGCACCCTGCTAAATCAAGCACTTCTTTTGACTTT
CTGGAGCTAAATTACAGTTTTGACAAAAATGCTGACACAACCATGAAATGGCAGACAAAG
GCATTTCCAATAGTTGGGGAGCCTCTTCAGAAGCATCAAAGTTTGGATTTGGGCTCTCTT
TTGTTTGAGGGATGTTCTAATTCTAAACCTGTAAATGCAGCAGGAAGATATTTTAATTCA
AAGGTGCCAATAACACGGACCAAATCAACTCCTTTTGAATTGATACAGCAGAGAGAAACC
AAGGAGGTGGACAGCAAGGAAAACTTTTCTTATTTGGAATCTCAACCACATGATTCTTGT
TTTGTAGAGATGCAGGCTCAAAAAGTAATGCATGTTTCTTCAGCAGAACTGAATTATTCA
CTGCCATATGACTCTAAACACCAAATACGTAATGCCTCTAATGTAAAGCACCATGACTCT
AGTGCTCTTGGTGTATATTCTTACATACCTTTAGTGGAAAATCCTTATTTTTCATCATGG
CCTCCAAGTGGTACCAGTTCTAAGATGTCTCTTGATTTACCTGAGAAGCAAGATGGAACT
GTTTTTCCTTCTTCTCTGTTGCCAACATCCTCTACATCCCTCTTCTCTTATTACAATTCA
CATGATTCTTTATCACTGAATTCTCCAACCAATATTTCCTCACTATTGAACCAGGAGTCA
GCTGTACTAGCAACTGCTCCAAGGATAGATGATGAAATCCCCCCTCCACTTCCTGTACGG
ACACCTGAATCATTTATTGTGGTTGAGGAAGCTGGAGAATTCTCACCAAATGTTCCCAAA
TCCTTATCCTCAGCTGTGAAGGTAAAAATTGGAACATCACTGGAATGGGGTGGAACATCT
GAACCAAAGAAATTTGATGACTCTGTGATACTTAGACCAAGCAAGAGTGTAAAACTCCGA
AGTCCTAAATCAGAACTACATCAAGATCGTTCTTCTCCCCCACCTCCTCTCCCAGAAAGA
ACTCTAGAGTCCTTCTTTCTTGCCGATGAAGATTGTATGCAGGCCCAATCTATAGAAACA
TATTCTACTAGCTATCCTGACACCATGGAAAATTCAACATCTTCAAAACAGACACTGAAG
ACTCCTGGAAAAAGTTTCACAAGGAGTAAGAGTTTGAAAATTTTGCGAAACATGAAAAAG
AGTATCTGTAATTCTTGCCCACCAAACAAGCCTGCAGAATCTGTTCAGTCAAATAACTCC
AGCTCATTTCTGAATTTTGGTTTTGCAAACCGTTTTTCAAAACCCAAAGGACCAAGGAAT
CCACCACCAACTTGGAATATTTAA
Protein Properties
Number of Residues 807
Molecular Weight 88646.45
Theoretical pI 7.445
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Tyrosine-protein phosphatase non-receptor type 22
MDQREILQKFLDEAQSKKITKEEFANEFLKLKRQSTKYKADKTYPTTVAEKPKNIKKNRY
KDILPYDYSRVELSLITSDEDSSYINANFIKGVYGPKAYIATQGPLSTTLLDFWRMIWEY
SVLIIVMACMEYEMGKKKCERYWAEPGEMQLEFGPFSVSCEAEKRKSDYIIRTLKVKFNS
ETRTIYQFHYKNWPDHDVPSSIDPILELIWDVRCYQEDDSVPICIHCSAGCGRTGVICAI
DYTWMLLKDGIIPENFSVFSLIREMRTQRPSLVQTQEQYELVYNAVLELFKRQMDVIRDK
HSGTESQAKHCIPEKNHTLQADSYSPNLPKSTTKAAKMMNQQRTKMEIKESSSFDFRTSE
ISAKEELVLHPAKSSTSFDFLELNYSFDKNADTTMKWQTKAFPIVGEPLQKHQSLDLGSL
LFEGCSNSKPVNAAGRYFNSKVPITRTKSTPFELIQQRETKEVDSKENFSYLESQPHDSC
FVEMQAQKVMHVSSAELNYSLPYDSKHQIRNASNVKHHDSSALGVYSYIPLVENPYFSSW
PPSGTSSKMSLDLPEKQDGTVFPSSLLPTSSTSLFSYYNSHDSLSLNSPTNISSLLNQES
AVLATAPRIDDEIPPPLPVRTPESFIVVEEAGEFSPNVPKSLSSAVKVKIGTSLEWGGTS
EPKKFDDSVILRPSKSVKLRSPKSELHQDRSSPPPPLPERTLESFFLADEDCMQAQSIET
YSTSYPDTMENSTSSKQTLKTPGKSFTRSKSLKILRNMKKSICNSCPPNKPAESVQSNNS
SSFLNFGFANRFSKPKGPRNPPPTWNI
GenBank ID Protein 224586929
UniProtKB/Swiss-Prot ID Q9Y2R2
UniProtKB/Swiss-Prot Entry Name PTN22_HUMAN
PDB IDs
GenBank Gene ID NM_015967.5
GeneCard ID PTPN22
GenAtlas ID PTPN22
HGNC ID HGNC:9652
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. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [PubMed:16710414 ]
  3. Barr AJ, Ugochukwu E, Lee WH, King ON, Filippakopoulos P, Alfano I, Savitsky P, Burgess-Brown NA, Muller S, Knapp S: Large-scale structural analysis of the classical human protein tyrosine phosphatome. Cell. 2009 Jan 23;136(2):352-63. doi: 10.1016/j.cell.2008.11.038. [PubMed:19167335 ]
  4. Cohen S, Dadi H, Shaoul E, Sharfe N, Roifman CM: Cloning and characterization of a lymphoid-specific, inducible human protein tyrosine phosphatase, Lyp. Blood. 1999 Mar 15;93(6):2013-24. [PubMed:10068674 ]
  5. Yu X, Sun JP, He Y, Guo X, Liu S, Zhou B, Hudmon A, Zhang ZY: Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19767-72. Epub 2007 Dec 3. [PubMed:18056643 ]
  6. Tsai SJ, Sen U, Zhao L, Greenleaf WB, Dasgupta J, Fiorillo E, Orru V, Bottini N, Chen XS: Crystal structure of the human lymphoid tyrosine phosphatase catalytic domain: insights into redox regulation . Biochemistry. 2009 Jun 9;48(22):4838-45. doi: 10.1021/bi900166y. [PubMed:19371084 ]
  7. Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE, Chang M, Ramos P, Baechler EC, Batliwalla FM, Novitzke J, Williams AH, Gillett C, Rodine P, Graham RR, Ardlie KG, Gaffney PM, Moser KL, Petri M, Begovich AB, Gregersen PK, Behrens TW: Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet. 2004 Sep;75(3):504-7. Epub 2004 Jul 23. [PubMed:15273934 ]
  8. Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M, MacMurray J, Meloni GF, Lucarelli P, Pellecchia M, Eisenbarth GS, Comings D, Mustelin T: A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet. 2004 Apr;36(4):337-8. Epub 2004 Mar 7. [PubMed:15004560 ]