protein tyrosine phosphatase 8/22, non-receptor type; PTPN8/22; hematopoietic cell protein-tyrosine phosphatase 70Z-PEP; lymphoid phosphatase; LyP (PTPN22, PTPN8)

Function: - seems to act on Cbl - may play a role in regulating function of Cbl & its associated protein kinases - negative regulator of T-cell receptor signaling by direct dephosphorylation of the Src family kinases LCK & FYN, ITAMs of the TCRz/CD3 complex, ZAP70, VAV, VCP - seems to dephosphorylate CBL - dephosphorylates LCK at its activating Y394 - dephosphorylates ZAP70 at its activating Y493 - dephosphorylates the immune system activator SKAP2 - positively regulates toll-like receptor-induced interferon type-1 production - promotes host antiviral responses mediated by interferon type-1 interferon (putative) - egulates NOD2-induced pro-inflammatory cytokine secretion & autophagy - down-regulated by phosphorylation - phosphorylation on Ser-35 by PKC/PRKCD abrogates its ability to dephosphorylate & inactivate the SRC family kinases - interacts with CSK - interacts with LPXN (putative) - interacts with TRAF3 (via MATH domain); the interaction promotes TRAF3 polyubiquitination Structure: - belongs to the protein-tyrosine phosphatase family non-receptor class 4 subfamily - contains 1 tyrosine-protein phosphatase domain Compartment: cytoplasm (putative) Alternative splicing: - named isoforms=6 - at least one isoform due to intron retention - at least one isoform lacks most of the phosphatase domain & functions as a dominant negative isoform Expression: - expressed in bone marrow, B & T-cells, NK cells, monocytes, dendritic cells & neutrophils - isoforms 1 & 4 predominantly expressed in lymphoid tissues & cells - isoform 1 is expressed in thymocytes & both mature B-cells & T-cells - expression induced by muramyl-dipeptide & lipopolysaccharide Pathology: - susceptibility to systemic lupus erythematosus is associated with variations in PTPN22 - susceptibility to diabetes mellitus type 1 is associated with variations in PTPN22 - susceptibility to rheumatoid arthritis is associated with variations in PTPN22 - susceptibility to vitiligo is associated with variations in PTPN22 Laboratory: - PTPN22 gene mutation

General

phosphoprotein tyrosine phosphatase, non-receptor type

Properties

SIZE: entity length = 807 aa MW = 92 kD COMPARTMENT: cytoplasm MOTIF: Tyr phosphatase {24-289} MOTIF: Ser phosphorylation site {S35} cysteine residue {C129} MODIFICATION: cysteine residue {C227} binding site SITE: 195-195 FOR-BINDING-OF: Substrate Substrate binding {227-233} cysteine residue {C227} cysteine residue {C227} MODIFICATION: cysteine residue {C129} binding site SITE: 274-274 FOR-BINDING-OF: Substrate Ser phosphorylation site {S449} Ser phosphorylation site {S635} Ser phosphorylation site {S684} Ser phosphorylation site {S692} STATE: active state

Database Correlations

OMIM correlations MORBIDMAP 600716 UniProt Q9Y2R2 Pfam PF00102 Entrez Gene 26191 Kegg hsa:26191 ENZYME 3.1.3.48

References

UniProt :accession Q9Y2R2