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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
Location 1p13.2      Physical location : 114.356.433 - 114.414.375
Synonym name
  • lymphoid protein tyrosine phosphatase
  • protein tyrosine phosphatase homolog
  • hematopoietic cell protein-tyrosine phosphatase 70Z-PEP
  • protein tyrosine phosphatase, non-receptor type 8
  • Synonym symbol(s) LYSP, LYP, CBLREG, PTPN8, LYP1, LYP2, PEP
    EC.number 3.1.3.48
    DNA
    TYPE functioning gene
    STRUCTURE 57.90 kb     21 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - MAGI3 - RSBN1 - PTPN22 - GM566 - AP4B1 - DCLRE1B - cen
    Authors Qu(05)
    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