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    PTPN22 protein tyrosine phosphatase, non-receptor type 22 [ Homo sapiens (human) ]

    Gene ID: 26191, updated on 7-May-2017
    Official Symbol
    PTPN22provided by HGNC
    Official Full Name
    protein tyrosine phosphatase, non-receptor type 22provided by HGNC
    Primary source
    HGNC:HGNC:9652
    See related
    Ensembl:ENSG00000134242 MIM:600716; Vega:OTTHUMG00000011936
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    LYP; PEP; LYP1; LYP2; PTPN8; PTPN22.5; PTPN22.6
    Summary
    This gene encodes of member of the non-receptor class 4 subfamily of the protein-tyrosine phosphatase family. The encoded protein is a lymphoid-specific intracellular phosphatase that associates with the molecular adapter protein CBL and may be involved in regulating CBL function in the T-cell receptor signaling pathway. Mutations in this gene may be associated with a range of autoimmune disorders including Type 1 Diabetes, rheumatoid arthritis, systemic lupus erythematosus and Graves' disease. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Mar 2009]
    Orthologs
    Location:
    1p13.2
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 1 NC_000001.11 (113813811..113871761, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (114356433..114414375, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ribosomal protein S2 pseudogene 14 Neighboring gene putative homeodomain transcription factor 1 Neighboring gene round spermatid basic protein 1 Neighboring gene AP4B1 antisense RNA 1 Neighboring gene BCL2 like 15 Neighboring gene adaptor related protein complex 4 beta 1 subunit Neighboring gene DNA cross-link repair 1B

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Diabetes mellitus type 1
    MedGen: C0011854 OMIM: 222100 GeneReviews: Not available
    Compare labs
    Rheumatoid arthritis
    MedGen: C0003873 OMIM: 180300 GeneReviews: Not available
    Compare labs
    Systemic lupus erythematosus
    MedGen: C0024141 OMIM: 152700 GeneReviews: Not available
    Compare labs

    NHGRI GWAS Catalog

    Description
    A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.
    NHGRI GWA Catalog
    A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.
    NHGRI GWA Catalog
    Common variants at CD40 and other loci confer risk of rheumatoid arthritis.
    NHGRI GWA Catalog
    Genetics of rheumatoid arthritis contributes to biology and drug discovery.
    NHGRI GWA Catalog
    Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.
    NHGRI GWA Catalog
    Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease.
    NHGRI GWA Catalog
    Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
    NHGRI GWA Catalog
    Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
    NHGRI GWA Catalog
    Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
    NHGRI GWA Catalog
    Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
    NHGRI GWA Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    NHGRI GWA Catalog
    Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease.
    NHGRI GWA Catalog
    Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
    NHGRI GWA Catalog
    Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci.
    NHGRI GWA Catalog
    Novel associations for hypothyroidism include known autoimmune risk loci.
    NHGRI GWA Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    NHGRI GWA Catalog
    Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study.
    NHGRI GWA Catalog
    REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.
    NHGRI GWA Catalog
    Risk for myasthenia gravis maps to a (151) Pro→Ala change in TNIP1 and to human leukocyte antigen-B*08.
    NHGRI GWA Catalog
    Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes.
    NHGRI GWA Catalog
    TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study.
    NHGRI GWA Catalog
    Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo.
    NHGRI GWA Catalog
    • Adaptive Immune System, organism-specific biosystem (from REACTOME)
      Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Phosphorylation of CD3 and TCR zeta chains, organism-specific biosystem (from REACTOME)
      Phosphorylation of CD3 and TCR zeta chains, organism-specific biosystemPrior to T cell receptor (TCR) stimulation, CD4/CD8 associated Lck remains seperated from the TCR and is maintained in an inactive state by the action of Csk. Csk phosphorylates the negative regulato...
    • TCR signaling, organism-specific biosystem (from REACTOME)
      TCR signaling, organism-specific biosystemThe TCR is a multisubunit complex that consists of clonotypic alpha/beta chains noncovalently associated with the invariant CD3 delta/epsilon/gamma and TCR zeta chains. T cell activation by antigen p...
    • Translocation of ZAP-70 to Immunological synapse, organism-specific biosystem (from REACTOME)
      Translocation of ZAP-70 to Immunological synapse, organism-specific biosystemThe dual phosphorylated ITAMs recruit Syk kinase ZAP-70 via their tandem SH2 domains (step 4). ZAP-70 subsequently undergoes phosphorylation on multiple tyrosine residues for further activation. ZAP-...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    SH3 domain binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    kinase binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    phosphatase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein tyrosine phosphatase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein tyrosine phosphatase activity TAS
    Traceable Author Statement
    more info
     
    ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    T cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    T cell receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    autophagy IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to muramyl dipeptide IDA
    Inferred from Direct Assay
    more info
    PubMed 
    lipopolysaccharide-mediated signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of JUN kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of T cell activation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of T cell receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of autophagy IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of interleukin-6 secretion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of interleukin-8 secretion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of p38MAPK cascade IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of tumor necrosis factor production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    peptidyl-tyrosine dephosphorylation IEA
    Inferred from Electronic Annotation
    more info
     
    phosphoanandamide dephosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of ERK1 and ERK2 cascade IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of interferon-gamma secretion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of protein K63-linked ubiquitination IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of toll-like receptor 3 signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of toll-like receptor 4 signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of type I interferon production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    protein dephosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein dephosphorylation TAS
    Traceable Author Statement
    more info
    PubMed 
    regulation of B cell receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    regulation of NIK/NF-kappaB signaling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of innate immune response IC
    Inferred by Curator
    more info
    PubMed 
    regulation of natural killer cell proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to lipopolysaccharide IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytoplasm TAS
    Traceable Author Statement
    more info
    PubMed 
    cytoplasmic side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    tyrosine-protein phosphatase non-receptor type 22
    Names
    PEST-domain phosphatase
    hematopoietic cell protein-tyrosine phosphatase 70Z-PEP
    lymphoid-specific protein tyrosine phosphatase
    protein tyrosine phosphatase, non-receptor type 22 (lymphoid)
    protein tyrosine phosphatase, non-receptor type 8
    NP_001180360.1
    NP_001295226.1
    NP_036543.4
    NP_057051.3
    XP_011539523.1
    XP_011539524.1
    XP_011539525.1
    XP_011539527.1
    XP_016856493.1
    XP_016856494.1
    XP_016856495.1

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011432.1 RefSeqGene

      Range
      4995..62943
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001193431.2NP_001180360.1  tyrosine-protein phosphatase non-receptor type 22 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate in-frame splice site in the central coding region, compared to variant 1, resulting in an isoform (3) that is shorter than isoform 1.
      Source sequence(s)
      AA836401, AF001846, AK303124, BC071670, CD692658, DB145424, GU479452
      UniProtKB/Swiss-Prot
      Q9Y2R2
      UniProtKB/TrEMBL
      B4DZW8
      Conserved Domains (2) summary
      smart00194
      Location:24288
      PTPc; Protein tyrosine phosphatase, catalytic domain
      cd00047
      Location:56288
      PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
    2. NM_001308297.1NP_001295226.1  tyrosine-protein phosphatase non-receptor type 22 isoform 4

      See identical proteins and their annotated locations for NP_001295226.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1, resulting in an isoform (4) that is shorter than isoform 1.
      Source sequence(s)
      AA836401, AF001846, BC071670, CD692658, DB145424, JN084012
      Consensus CDS
      CCDS76191.1
      UniProtKB/Swiss-Prot
      Q9Y2R2
      UniProtKB/TrEMBL
      G3K0T4
      Related
      ENSP00000439372.2, ENST00000538253.5
      Conserved Domains (2) summary
      smart00194
      Location:24264
      PTPc; Protein tyrosine phosphatase, catalytic domain
      cd00047
      Location:56264
      PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
    3. NM_012411.5NP_036543.4  tyrosine-protein phosphatase non-receptor type 22 isoform 2

      See identical proteins and their annotated locations for NP_036543.4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks two alternate in-frame exons in the central coding region, compared to variant 1, resulting in an isoform (2) that is shorter than isoform 1.
      Source sequence(s)
      AA836401, AF001846, BC071670, CD692658, DB145424
      Consensus CDS
      CCDS864.2
      UniProtKB/Swiss-Prot
      Q9Y2R2
      Related
      ENSP00000435176.1, OTTHUMP00000013721, ENST00000528414.5, OTTHUMT00000033018
      Conserved Domains (2) summary
      cd00047
      Location:56252
      PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
      pfam00102
      Location:54291
      Y_phosphatase; Protein-tyrosine phosphatase
    4. NM_015967.6NP_057051.3  tyrosine-protein phosphatase non-receptor type 22 isoform 1

      See identical proteins and their annotated locations for NP_057051.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AA836401, AF001846, AF077031, AK303124, AL137856, BC071670, CD692658, DB145424
      Consensus CDS
      CCDS863.1
      UniProtKB/Swiss-Prot
      Q9Y2R2
      UniProtKB/TrEMBL
      B4DZW8
      Related
      ENSP00000352833.5, OTTHUMP00000013720, ENST00000359785.9, OTTHUMT00000033015
      Conserved Domains (2) summary
      smart00194
      Location:24288
      PTPc; Protein tyrosine phosphatase, catalytic domain
      cd00047
      Location:56288
      PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p7 Primary Assembly

      Range
      113813811..113871761 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011541225.2XP_011539527.1  tyrosine-protein phosphatase non-receptor type 22 isoform X7

      Conserved Domains (2) summary
      smart00194
      Location:24264
      PTPc; Protein tyrosine phosphatase, catalytic domain
      cd00047
      Location:56264
      PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
    2. XM_011541221.1XP_011539523.1  tyrosine-protein phosphatase non-receptor type 22 isoform X1

      Conserved Domains (2) summary
      smart00194
      Location:24262
      PTPc; Protein tyrosine phosphatase, catalytic domain
      cd00047
      Location:56262
      PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
    3. XM_011541222.1XP_011539524.1  tyrosine-protein phosphatase non-receptor type 22 isoform X2

      Conserved Domains (2) summary
      smart00194
      Location:24288
      PTPc; Protein tyrosine phosphatase, catalytic domain
      cd00047
      Location:56288
      PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
    4. XM_017001005.1XP_016856494.1  tyrosine-protein phosphatase non-receptor type 22 isoform X5

    5. XM_017001004.1XP_016856493.1  tyrosine-protein phosphatase non-receptor type 22 isoform X3

      Related
      ENSP00000388229.2, OTTHUMP00000233450, ENST00000420377.6, OTTHUMT00000390435
    6. XM_011541223.2XP_011539525.1  tyrosine-protein phosphatase non-receptor type 22 isoform X4

      Conserved Domains (2) summary
      smart00194
      Location:24288
      PTPc; Protein tyrosine phosphatase, catalytic domain
      cd00047
      Location:56288
      PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
    7. XM_017001006.1XP_016856495.1  tyrosine-protein phosphatase non-receptor type 22 isoform X6

    Alternate CHM1_1.1

    Genomic

    1. NC_018912.2 Alternate CHM1_1.1

      Range
      114471278..114529231 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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