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target has curated data in GtoImmuPdb
Target id: 3084
Nomenclature: protein tyrosine phosphatase non-receptor type 22
Abbreviated Name: LYP
Systematic Nomenclature: PTPN22
Family: Protein tyrosine phosphatases non-receptor type (PTPN)
Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | - | 807 | 1p13.2 | PTPN22 | protein tyrosine phosphatase non-receptor type 22 | 4 |
| Mouse | - | 802 | 3 F2.2 | Ptpn22 | protein tyrosine phosphatase, non-receptor type 22 (lymphoid) | |
| Rat | - | 804 | 2q34 | Ptpn22 | protein tyrosine phosphatase, non-receptor type 22 | |
| Gene and Protein Information Comments | ||||||
| Alternatively spliced transcript variants encoding distinct isoforms have been described for the human gene. | ||||||
| Previous and Unofficial Names |
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| protein tyrosine phosphatase, non-receptor type 22 | protein tyrosine phosphatase, non-receptor type 22 (lymphoid) | protein tyrosine phosphatase | Lyp1 | Lyp2 (85 kDa splice variant) [4] | protein tyrosine phosphatase, non-receptor type 8 | PTPN8 | 70zPEP (mouse homologue) | |
| Database Links |
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| Alphafold | Q9Y2R2 (Hs), P29352 (Mm) |
| BRENDA | 3.1.3.48 |
| ChEMBL Target | CHEMBL2889 (Hs), CHEMBL2157855 (Mm) |
| Ensembl Gene | ENSG00000134242 (Hs), ENSMUSG00000027843 (Mm), ENSRNOG00000019614 (Rn) |
| Entrez Gene | 26191 (Hs), 19260 (Mm), 295338 (Rn) |
| Human Protein Atlas | ENSG00000134242 (Hs) |
| KEGG Enzyme | 3.1.3.48 |
| KEGG Gene | hsa:26191 (Hs), mmu:19260 (Mm), rno:295338 (Rn) |
| OMIM | 600716 (Hs) |
| Pharos | Q9Y2R2 (Hs) |
| RefSeq Nucleotide | NM_015967 (Hs), NM_008979 (Mm), NM_001106460 (Rn) |
| RefSeq Protein | NP_057051 (Hs), NP_033005 (Mm), NP_001099930 (Rn) |
| UniProtKB | Q9Y2R2 (Hs), P29352 (Mm) |
| Wikipedia | PTPN22 (Hs) |
| Enzyme Reaction |
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Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immunopharmacology Comments |
| PTPN22 is a lymphoid-specific, inducible protein tyrosine phosphatase [4]. It negatively regulates T-cell receptor (TCR) signalling via direct dephosphorylation of phospho-tyrosines on a number of key signalling proteins, including LCK [14], FYN, and ZAP70 [13] (kinases), ITAM domains of the TCRζ/CD3 complex, and several other signalling proteins [12-13,15]. Biochemical studies suggest that dephosphorylation of the TCR-associated LCK and ZAP70 tyrosine kinases is the principal PTPN22 mechanism that contributes to inhibiting T cell activation [3,6,13]. The Arg620Trp (R620W) variant of PTPN22, which exhibits more active phosphatease activity, is highly correlated with a spectrum of autoimmune diseases. In mice, reduced PTPN22 activity augments antitumour activity by increasing infiltration and activation of macrophages, natural killer cells, and T cells within the tumour mocroenvironment [8]. This information suggests that PTPN22 can be considered as a target for cancer immunotherapy. Selective inhibitors of PTPN22 are currently being sought as tool compounds to extend functional characterisation studies of PTPN22 in human diseases. |
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| Biologically Significant Variants
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1. Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC, Ardlie KG, Huang Q, Smith AM, Spoerke JM et al.. (2004) A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet, 75 (2): 330-7. [PMID:15208781]
2. Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M, MacMurray J, Meloni GF, Lucarelli P, Pellecchia M et al.. (2004) A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet, 36 (4): 337-8. [PMID:15004560]
3. Cloutier JF, Veillette A. (1999) Cooperative inhibition of T-cell antigen receptor signaling by a complex between a kinase and a phosphatase. J Exp Med, 189 (1): 111-21. [PMID:9874568]
4. Cohen S, Dadi H, Shaoul E, Sharfe N, Roifman CM. (1999) Cloning and characterization of a lymphoid-specific, inducible human protein tyrosine phosphatase, Lyp. Blood, 93 (6): 2013-24. [PMID:10068674]
5. Criswell LA, Pfeiffer KA, Lum RF, Gonzales B, Novitzke J, Kern M, Moser KL, Begovich AB, Carlton VE, Li W et al.. (2005) Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes. Am J Hum Genet, 76 (4): 561-71. [PMID:15719322]
6. Gjörloff-Wingren A, Saxena M, Williams S, Hammi D, Mustelin T. (1999) Characterization of TCR-induced receptor-proximal signaling events negatively regulated by the protein tyrosine phosphatase PEP. Eur J Immunol, 29 (12): 3845-54. [PMID:10601992]
7. He Y, Liu S, Menon A, Stanford S, Oppong E, Gunawan AM, Wu L, Wu DJ, Barrios AM, Bottini N et al.. (2013) A potent and selective small-molecule inhibitor for the lymphoid-specific tyrosine phosphatase (LYP), a target associated with autoimmune diseases. J Med Chem, 56 (12): 4990-5008. [PMID:23713581]
8. Ho WJ, Croessmann S, Lin J, Phyo ZH, Charmsaz S, Danilova L, Mohan AA, Gross NE, Chen F, Dong J et al.. (2021) Systemic inhibition of PTPN22 augments anticancer immunity. J Clin Invest, 131 (17) [Epub ahead of print]. [PMID:34283806]
9. Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE, Chang M, Ramos P, Baechler EC, Batliwalla FM et al.. (2004) Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet, 75 (3): 504-7. [PMID:15273934]
10. Li K, Hou X, Li R, Bi W, Yang F, Chen X, Xiao P, Liu T, Lu T, Zhou Y et al.. (2019) Identification and structure-function analyses of an allosteric inhibitor of the tyrosine phosphatase PTPN22. J Biol Chem, 294 (21): 8653-8663. [PMID:30979725]
11. Velaga MR, Wilson V, Jennings CE, Owen CJ, Herington S, Donaldson PT, Ball SG, James RA, Quinton R, Perros P et al.. (2004) The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves' disease. J Clin Endocrinol Metab, 89 (11): 5862-5. [PMID:15531553]
12. Wang Y, Shaked I, Stanford SM, Zhou W, Curtsinger JM, Mikulski Z, Shaheen ZR, Cheng G, Sawatzke K, Campbell AM et al.. (2013) The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity. Immunity, 39 (1): 111-22. [PMID:23871208]
13. Wu J, Katrekar A, Honigberg LA, Smith AM, Conn MT, Tang J, Jeffery D, Mortara K, Sampang J, Williams SR et al.. (2006) Identification of substrates of human protein-tyrosine phosphatase PTPN22. J Biol Chem, 281 (16): 11002-10. [PMID:16461343]
14. Yu X, Chen M, Zhang S, Yu ZH, Sun JP, Wang L, Liu S, Imasaki T, Takagi Y, Zhang ZY. (2011) Substrate specificity of lymphoid-specific tyrosine phosphatase (Lyp) and identification of Src kinase-associated protein of 55 kDa homolog (SKAP-HOM) as a Lyp substrate. J Biol Chem, 286 (35): 30526-34. [PMID:21719704]
15. Yu X, Sun JP, He Y, Guo X, Liu S, Zhou B, Hudmon A, Zhang ZY. (2007) Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases. Proc Natl Acad Sci USA, 104 (50): 19767-72. [PMID:18056643]
Protein tyrosine phosphatases non-receptor type (PTPN): protein tyrosine phosphatase non-receptor type 22. Last modified on 26/07/2021. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3084.
