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Protein / target

Tyrosine-protein phosphatase non-receptor type 22

Encoded byPTPN22Q9Y2R2Homo sapiensSwiss-Prot
UniProt: Q9Y2R2Ensembl: ENSG00000134242HGNC: HGNC:9652NCBI Gene: 26191
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

Non-membrane spanning protein tyrosine phosphatase

Strongest disease association

Hypothyroidism

Via encoding gene PTPN22 · Genetic evidence · score 0.89

Research activity

Emerging research

1 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Acts as a negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules.

View complete UniProt function annotation

Acts as a negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules (PubMed:16461343, PubMed:18056643). Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue (PubMed:21719704). Dephosphorylates ZAP70 at its activating 'Tyr-493' residue (PubMed:16461343). Dephosphorylates the immune system activator SKAP2 (PubMed:21719704). Positively regulates toll-like receptor (TLR)-induced type 1 interferon production (PubMed:23871208). Promotes host antiviral responses mediated by type 1 interferon (By similarity). Regulates NOD2-induced pro-inflammatory cytokine secretion and autophagy (PubMed:23991106). Acts as an activator of NLRP3 inflammasome assembly by mediating dephosphorylation of 'Tyr-861' of NLRP3 (PubMed:27043286). Dephosphorylates phospho-anandamide (p-AEA), an endocannabinoid to anandamide (also called N-arachidonoylethanolamide) (By similarity)

Subcellular location

Cytoplasm
Domains and Gene Ontology detail (42)

Domains & features

Tyrosine-protein phosphatase

Gene Ontology

  • Ccytoplasm
  • Ccytoplasmic side of plasma membrane
  • Ccytosol
  • Cnucleus
  • Cperinuclear region of cytoplasm
  • Fkinase binding
  • Fnon-membrane spanning protein tyrosine phosphatase activity
  • Fphosphatase activity
  • Fprotein tyrosine phosphatase activity
  • FSH3 domain binding
  • Fubiquitin protein ligase binding
  • Pautophagy

807 aa · 92 kDa · 6 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismGOImmune signallingUniProt · GOTranscriptional regulationGO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·lipid metabolic process

Immune signalling

  • ·Acts as a negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylat…
  • ·negative regulation of interleukin-6 production
  • ·negative regulation of interleukin-8 production
  • ·negative regulation of T cell activation

Transcriptional regulation

  • ·negative regulation of gene expression
  • ·positive regulation of gene expression

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene PTPN22

Gene-level evidence surfaced through the gene PTPN22 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Hypothyroidism
0.89Well supported

Genetic evidence dominant · Open Targets 0.54

Crohn's Disease
0.83Well supported

Genetic evidence dominant · Open Targets 0.51

Diabetes Mellitus
0.82Well supported

Genetic evidence dominant · Open Targets 0.50

Arthritis, Rheumatoid
0.81Well supported

Genetic evidence dominant · Open Targets 0.67

Diabetes Mellitus, Type 1
0.80Well supported

Genetic evidence dominant · Open Targets 0.61

View evidence synthesis (5)
HypothyroidismWell supported
0.89
agreement 0.75–1.00
Genetic98%Literature2%

Open Targets aggregate 0.54 · 2 independent evidence families

Crohn's DiseaseWell supported
0.83
agreement 0.69–0.97
Genetic96%Literature4%

Open Targets aggregate 0.51 · 2 independent evidence families

Diabetes MellitusWell supported
0.82
agreement 0.68–0.96
Genetic94%Literature6%

Open Targets aggregate 0.50 · 2 independent evidence families

Arthritis, RheumatoidWell supported
0.81
agreement 0.68–0.94
Genetic84%Literature16%RNA expression1%Genetic literaturedup

Open Targets aggregate 0.67 · 3 independent evidence families · 1 not counted as duplicate

Diabetes Mellitus, Type 1Well supported
0.80
agreement 0.67–0.92
Genetic83%Literature16%RNA expression1%Genetic literaturedup

Open Targets aggregate 0.61 · 3 independent evidence families · 1 not counted as duplicate

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Arthritis, Rheumatoid0.67
Lupus Erythematosus, Systemic0.62
Diabetes Mellitus, Type 10.61
Hypothyroidism0.54
Autoimmune Diseases0.53
Vitiligo0.53
Thyroid Diseases0.52
Hashimoto's Disease0.51
Crohn's Disease0.51
Diabetes Mellitus0.50

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (7)
SM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketSM · Druggable FamilyPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

The genetics of Graves' disease.28 cites

Grixti L · Reviews in endocrine & metabolic disorders · 2024

Recent

The genetics of Graves' disease.

Grixti L · Reviews in endocrine & metabolic disorders · 2024

Europe PMC papers linked directly to this protein.