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FLASH GENE
Symbol PTPN22 contributors: mct/npt - updated : 15-06-2009
HGNC name protein tyrosine phosphatase, non-receptor type 22 (lymphoid)
HGNC id 9652
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
21 splicing 3644 91.7 807 - Cohen (1999)
having a distinct C terminus, 116AA longer
16 splicing 2347 78.7 691 - Cohen (1999)
116AA shorter than isoform 1, alternative splice site within the coding region, resulting in a frameshift and using of an upstream stop codon
EXPRESSION
Type restricted
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunelymph node    
 thymus    
Reproductivemale systemtestis   
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Lymphoid    
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a single tyrosine phosphatase catalytic domain
  • a non catalytic domain
  • four proline-rich potential SH3 domain binding sites
  • NXX4 motif
  • a consensus protein kinase C (PKC) phosphorylation site (Ser-35)(can be phosphorylated by PKC on Ser-35, which impairs the PTPN22-mediated substrate dephosphorylation and signaling in T cell)
  • HOMOLOGY
    interspecies homolog to murine Ptpn8
    Homologene
    FAMILY
  • protein-tyrosine phosphatase family
  • non-receptor class 4 subfamily
  • CATEGORY enzyme , immunity/defense , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • tyrosine phosphatase, non receptor, involved in regulation of the function of protooncogene CBL in the T-cell receptor signaling pathway
  • playing a role in regulating the immune system and the development of the autoimmunity
  • involved in preventing spontaneous T-cell activation by dephosphorylating and inactivating T-cell receptor-associated CSK kinase
  • inhibits secondary T cell responses by suppressing Src family protein tyrosine kinases and is implicated in autoimmunity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text anti-pathogen response (response to pest/pathogen/parasite)
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • CBl
  • cell & other
    REGULATION
    inhibited by PKC (could negatively regulate the cellular function of PTPN22, thereby augmenting T cell activation)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation     gain of function
    R620W, in type 1 diabetes, rheumatoid arthritis, lupus, Graves thyroiditis, Addison disease and other autoimmune disorders
    Susceptibility
  • to rheumatoid arthritis
  • to type 1 diabetes
  • to systemic lupus erythematosus (SLE) and Hashimoto thyroiditis
  • to type I psoriasis
  • to psoriasis (minor role)
  • to autoimmunity
  • to Addison disease
  • to vitiligo
  • Variant & Polymorphism SNP , other
  • allele 1858C
  • polymorphism R620W increasing the risk of SLE, rheumatoid arthritis, type 1 diabetes and Hashimoto thyroiditis
  • promoter SNP 1123G>C associated to type 1 diabetes
  • lacking the C allele may have reduced capacity to downregulate T-cell responses and may therefore be more susceptible to autoimmunity
  • T allele encoding the 620W residue is associated with an increased risk for developing type 1 diabetes
  • association of the 1858T-allele with Addison disease
  • Q263 variant conferred protection against systemic lupus erythematosus, reinforcing the proposal that inhibition of PTPN22 activity could be beneficial in autoimmunity (Orru 2009)
  • two SNPs (rs1217414 and rs3789604) demonstrated significant association with type I psoriasis (Smith 2008)
  • PTPN22 1858T allele of SNP rs2476601 is significantly associated both with generalized vitiligo and with an expanded autoimmunity phenotype
  • Candidate gene potential target for a broad spectrum of autoimmune disorders
    Marker
    Therapy target
    ANIMAL & CELL MODELS