PTPN22

Protein tyrosine phosphatase, non-receptor type 22 (lymphoid), also known as PTPN22, is a protein that in humans is encoded by the PTPN22 gene.[5][6][7] This gene can be expressed in different forms. PTPN22 affects the responsiveness of T and B cell receptors, and mutations are associated with increases or decreases in risks of autoimmune diseases.

PTPN22
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPTPN22, protein tyrosine phosphatase, non-receptor type 22 (lymphoid), LYP, LYP1, LYP2, PEP, PTPN8, protein tyrosine phosphatase, non-receptor type 22, PTPN22.6, PTPN22.5, protein tyrosine phosphatase non-receptor type 22
External IDsOMIM: 600716 MGI: 107170 HomoloGene: 7498 GeneCards: PTPN22
Gene location (Human)
Chr.Chromosome 1 (human)[1]
Band1p13.2Start113,813,811 bp[1]
End113,871,753 bp[1]
RNA expression pattern




More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

26191

19260

Ensembl

ENSG00000134242

ENSMUSG00000027843

UniProt

Q9Y2R2

P29352

RefSeq (mRNA)

NM_001193431
NM_001308297
NM_012411
NM_015967

NM_008979

RefSeq (protein)

NP_001180360
NP_001295226
NP_036543
NP_057051

NP_033005

Location (UCSC)Chr 1: 113.81 – 113.87 MbChr 3: 103.86 – 103.91 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Molecular biology

The gene is located on the short arm of Chromosome 1 near the centromere (1p13.2) on the Crick (minus) strand. It is 57,898 bases in length and encodes a protein of 807 amino acids (molecular weight 91,705 Da). There are 24 exons in the gene and 21 transcript variants encoding 10 distinct proteins are known. The proteins are located in the cytoplasm.

Function

This gene encodes a protein tyrosine phosphatase which is expressed primarily in lymphoid tissues. This enzyme is involved in several signalling pathways associated with the immune response. Based on models of the murine phosphatase,[8][9] structural identification,[10] and human genetics[11] the phosphatase forms complexes with C-src tyrosine kinase (Csk), associated with the control of Src family members. The mutation Arg620Trp disrupts binding to Csk, alters the responsiveness of T and B cell receptors, and is associated with autoimmune diseases. There are other suggestions that the phosphatase regulates CBL function in the T cell receptor signaling pathway.[5] Other interactions are likely.

Disease association

The common 1858T (rs2476601) Arg620Trp nonsynonymous single nucleotide polymorphism located in the PTPN22 gene has been associated with autoimmune disorders, including an increased risk of Type 1 Diabetes, rheumatoid arthritis, lupus, Vitiligo and Graves' disease, but a decreased risk of Crohn's disease.[12][13]

A recent study suggests that the mutation does not, on a population basis, reduce life span.[14] The mutation may be conserved in human evolution because it may provide a hyper-immune response to infectious disease.[15]

Mutations in PTPN22 are over-represented in breast cancer.[16]

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References
  1. GRCh38: Ensembl release 89: ENSG00000134242 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000027843 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. EntrezGene 26191
  6. Matthews RJ, Bowne DB, Flores E, Thomas ML (May 1992). "Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences". Mol. Cell. Biol. 12 (5): 2396–405. doi:10.1128/mcb.12.5.2396. PMC 364412. PMID 1373816.
  7. Cohen S, Dadi H, Shaoul E, Sharfe N, Roifman CM (March 1999). "Cloning and characterization of a lymphoid-specific, inducible human protein tyrosine phosphatase, Lyp". Blood. 93 (6): 2013–24. doi:10.1182/blood.V93.6.2013.406k25_2013_2024. PMID 10068674.
  8. Cloutier JF, Veillette A (September 1996). "Association of inhibitory tyrosine protein kinase p50csk with protein tyrosine phosphatase PEP in T cells and other hemopoietic cells". EMBO J. 15 (18): 4909–18. doi:10.1002/j.1460-2075.1996.tb00871.x. PMC 452228. PMID 8890164.
  9. Gregorieff A, Cloutier JF, Veillette A (May 1998). "Sequence requirements for association of protein-tyrosine phosphatase PEP with the Src homology 3 domain of inhibitory tyrosine protein kinase p50(csk)". J. Biol. Chem. 273 (21): 13217–22. doi:10.1074/jbc.273.21.13217. PMID 9582365.
  10. Ghose R, Shekhtman A, Goger MJ, Ji H, Cowburn D (November 2001). "A novel, specific interaction involving the Csk SH3 domain and its natural ligand". Nat. Struct. Biol. 8 (11): 998–1004. doi:10.1038/nsb1101-998. PMID 11685249.
  11. Vang T, Miletic AV, Bottini N, Mustelin T (September 2007). "Protein tyrosine phosphatase PTPN22 in human autoimmunity". Autoimmunity. 40 (6): 453–61. doi:10.1080/08916930701464897. PMID 17729039.
  12. Qu H, Tessier MC, Hudson TJ, Polychronakos C (March 2005). "Confirmation of the association of the R620W polymorphism in the protein tyrosine phosphatase PTPN22 with type 1 diabetes in a family based study". J. Med. Genet. 42 (3): 266–70. doi:10.1136/jmg.2004.026971. PMC 1736025. PMID 15744042.
  13. Vang T, Congia M, Macis MD, Musumeci L, Orrú V, Zavattari P, Nika K, Tautz L, Taskén K, Cucca F, Mustelin T, Bottini N (December 2005). "Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant". Nat. Genet. 37 (12): 1317–9. doi:10.1038/ng1673. PMID 16273109.
  14. Napolioni V, Natali A, Saccucci P, Lucarini N (August 2011). "PTPN22 1858C>T (R620W) functional polymorphism and human longevity". Mol. Biol. Rep. 38 (6): 4231–5. doi:10.1007/s11033-010-0546-8. PMID 21113673.
  15. "PTPN22". NLM (US Gov). Retrieved 5 April 2013.
  16. Koboldt DC (2012). "Comprehensive molecular portraits of human breast tumours". Nature. Nature Publishing Group. 490 (7418): 61–70. doi:10.1038/nature11412. PMC 3465532. PMID 23000897.

Further reading

Overview of all the structural information available in the PDB for UniProt: Q9Y2R2 (Tyrosine-protein phosphatase non-receptor type 22) at the PDBe-KB.

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