PTPN22

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Protein tyrosine phosphatase, non-receptor type 22 (lymphoid)
Protein PTPN22 PDB 2p6x.png
PDB rendering based on 2p6x.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PTPN22 ; LYP; LYP1; LYP2; PEP; PTPN8
External IDs OMIM600716 MGI107170 HomoloGene7498 ChEMBL: 2889 GeneCards: PTPN22 Gene
EC number 3.1.3.48
RNA expression pattern
PBB GE PTPN22 206060 s at tn.png
PBB GE PTPN22 208010 s at tn.png
PBB GE PTPN22 208011 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 26191 19260
Ensembl ENSG00000134242 ENSMUSG00000027843
UniProt Q9Y2R2 P29352
RefSeq (mRNA) NM_001193431 NM_008979
RefSeq (protein) NP_001180360 NP_033005
Location (UCSC) Chr 1:
114.36 – 114.41 Mb
Chr 3:
103.86 – 103.91 Mb
PubMed search [1] [2]

Protein tyrosine phosphatase, non-receptor type 22 (lymphoid), also known as PTPN22, is a protein that in humans is encoded by the PTPN22 gene.[1][2][3] 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.

Molecular biology[edit]

The gene is located on the short arm of Chromosome 1 near the end (telomere) (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.[citation needed]

Function[edit]

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,[4][5] structural identification,[6] and human genetics[7] 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.[1] Other interactions are likely.

Disease association[edit]

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, Systemic Lupus Erythematosus, Vitiligo and Graves' disease, but a decreased risk of Crohn's disease.[8][9]

A recent study suggests that the mutation does not, on a population basis, reduce life span.[10] The mutation may be conserved in human evolution because it may provide a hyper-immune response to infectious disease.[11]

Mutations in CCND3 are implicated in cases of breast cancer.[12]

References[edit]

  1. ^ a b EntrezGene 26191
  2. ^ 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. PMC 364412. PMID 1373816. 
  3. ^ 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. PMID 10068674. 
  4. ^ 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. PMC 452228. PMID 8890164. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ Vang T, Congia M, Macis MD, Musumeci L, Orrú V, Zavattari P et al. (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. 
  10. ^ 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. 
  11. ^ "PTPN22". NLM (US Gov). Retrieved 5 April 2013. 
  12. ^ "Comprehensive molecular portraits of human breast tumours". Nature (Nature Publishing Group) 490 (7418): 61–70. 2012. doi:10.1038/nature11412. PMC 3465532. PMID 23000897. 

Further reading[edit]