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

Gene ID: 26191, updated on 5-Aug-2018

Summary

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]
Expression
Biased expression in bone marrow (RPKM 9.6), lymph node (RPKM 7.9) and 13 other tissues See more
Orthologs

Genomic context

See PTPN22 in Genome Data Viewer
Location:
1p13.2
Exon count:
24
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 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 subunit beta 1 Neighboring gene DNA cross-link repair 1B

Genomic regions, transcripts, and products

Expression

  • 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

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

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

Pathways from BioSystems

  • 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-...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

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 

General protein information

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

NCBI Reference Sequences (RefSeq)

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 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p12 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_017001005.2XP_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

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