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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)
    Physical map
    ST7L 1p12 suppression of tumorigenicity 7 like CAPZA1 1p13.1 capping protein (actin filament) muscle Z-line, alpha 1 MRPL53P1 1p13.2 capping protein (actin filament) muscle Z-line, alpha 1 MOV10 1p13.1 Mov10, Moloney leukemia virus 10, homolog (mouse) ARHC 1p21-p13 ras homolog gene family, member C LOC284467 1p13.1 TAFA3 MGC19531 1p13.1 hypothetical protein MGC19531 LOC128322 1p13.1 similar to Nuclear transport factor 2 (NTF-2) (Placental protein 15) (PP15) LOC388666 1 hypothetical gene supported by AK093435 SLC16A1 1p13.2-p12 solute carrier family 16 (monocarboxylic acid transporters), member 1 LRIG2 1p13.1 leucine-rich repeats and immunoglobulin-like domains 2 RPS19P2 1p13.1 ribosomal protein S19 pseudogene 2 MAGI-3 1p12-p11.2 membrane-associated guanylate kinase-related (MAGI-3) PHTF1 1p13-p11 putative homeodomain transcription factor 1 FLJ11220 1p13.1 hypothetical protein FLJ11220 PTPN22 1p13.3-p13.1 protein tyrosine phosphatase, non-receptor type 22 (lymphoid) LOC148280 1p13.1 hypothetical LOC148280 AP4B1 1p11.2 adaptor-related protein complex 4, beta 1 subunit DCLRE1B 1p11.2 DNA cross-link repair 1B (PSO2 homolog, S. cerevisiae) HIPK1 1p12 DNA cross-link repair 1B (PSO2 homolog, S. cerevisiae) HNOEL-iso 1p13.1 HNOEL-iso protein SYT6 1p13.1 synaptotagmin VI MRP63P1 1p13.1 mitochondrial ribosomal protein 63 pseudogene 1 LOC391067 1 LOC391067 TRIM33 1p13.1 tripartite motif-containing 33 LOC347675 1p13.1 eukaryotic translation initiation factor 2 beta-like pseudogene LOC339395 1p13.1 similar to Pyruvate kinase, M2 isozyme BCAS2 1p21-p13.3 breast carcinoma amplified sequence 2 FLJ37099 1p13.1 FLJ37099 protein AMPD1 1p13 adenosine monophosphate deaminase 1 (isoform M) NRAS 1p13.2 neuroblastoma RAS viral (v-ras) oncogene homolog D1S155E 1p22 NRAS-related gene FLJ21168 1p13.1 hypothetical protein FLJ21168 SYCP1 1p13 synaptonemal complex protein 1
    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