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Protein / target

Tyrosine-protein phosphatase non-receptor type 2

Encoded byPTPN2P17706Homo sapiensSwiss-Prot
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

Diabetes Mellitus, Type 1

Via encoding gene PTPN2 · Genetic evidence · score 0.76

Research activity

Emerging research

1 papers · latest 2023

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

Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR.

View complete UniProt function annotation

Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3 and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the development of the immune system. Functions in T-cell receptor signaling through dephosphorylation of FYN and LCK to control T-cells differentiation and activation. Dephosphorylates CSF1R, negatively regulating its downstream signaling and macrophage differentiation. Negatively regulates cytokine (IL2/interleukin-2 and interferon)-mediated signaling through dephosphorylation of the cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that propagate signaling downstream of the cytokine receptors. Also regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine signaling through dephosphorylation of STAT3 and STAT6 respectively. In addition to the immune system, it is involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth. Activated by the integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates EGF signaling. Dephosphorylates PDGFRB and negatively regulates platelet-derived growth factor receptor-beta signaling pathway and therefore cell proliferation. Negatively regulates tumor necrosis factor-mediated signaling downstream via MAPK through SRC dephosphorylation. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of the hepatocyte growth factor receptor MET. Also plays an important role in glucose homeostasis. For instance, negatively regulates the insulin receptor signaling pathway through the dephosphorylation of INSR and control gluconeogenesis and liver glucose production through negative regulation of the IL6 signaling pathways. May also bind DNA

Subcellular location

Endoplasmic reticulumEndoplasmic reticulum-Golgi intermediate compartmentNucleusCytoplasmCell membrane
Domains and Gene Ontology detail (48)

Domains & features

Tyrosine-protein phosphatase

Gene Ontology

  • Ccytoplasm
  • Ccytosol
  • Cendoplasmic reticulum
  • Cendoplasmic reticulum-Golgi intermediate compartment
  • Cendosome lumen
  • Cnucleoplasm
  • Cnucleus
  • Cplasma membrane
  • Fintegrin binding
  • Fnon-membrane spanning protein tyrosine phosphatase activity
  • Fprotein kinase binding
  • Fprotein tyrosine phosphatase activity

415 aa · 48 kDa · 4 isoforms

Biological roles

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

Growth-factor signallingUniProt · GOReceptor tyrosine kinase signallingUniProt · GOCell proliferation & survivalGOCell migrationGOImmune signallingUniProt · GO
View supporting evidence

Growth-factor signalling

  • ·Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein t…
  • ·negative regulation of epidermal growth factor receptor signaling pathway
  • ·regulation of hepatocyte growth factor receptor signaling pathway

Receptor tyrosine kinase signalling

  • ·Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein t…
  • ·receptor tyrosine kinase binding

Cell proliferation & survival

  • ·negative regulation of cell population proliferation

Cell migration

  • ·negative regulation of chemotaxis

Immune signalling

  • ·Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein t…
  • ·B cell differentiation
  • ·negative regulation of inflammatory response
  • ·negative regulation of interleukin-2-mediated signaling pathway

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 PTPN2

Gene-level evidence surfaced through the gene PTPN2 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.

Arthritis, Rheumatoid
0.79Well supported

Genetic evidence dominant · Open Targets 0.48

Diabetes Mellitus, Type 1
0.78Well supported

Genetic evidence dominant · Open Targets 0.48

Inflammatory Bowel Diseases
0.75Well supported

Genetic evidence dominant · Open Targets 0.46

Crohn's Disease
0.75Well supported

Genetic evidence dominant · Open Targets 0.46

Autoimmune Diseases
0.73Moderately supported

Genetic evidence dominant · Open Targets 0.45

View evidence synthesis (5)
Arthritis, RheumatoidWell supported
0.79
agreement 0.660.91
Genetic87%Literature13%RNA expression0%

Open Targets aggregate 0.48 · 3 independent evidence families

Diabetes Mellitus, Type 1Well supported
0.78
agreement 0.640.92
Genetic90%Literature10%

Open Targets aggregate 0.48 · 2 independent evidence families

Inflammatory Bowel DiseasesWell supported
0.75
agreement 0.610.89
Genetic87%Literature13%

Open Targets aggregate 0.46 · 2 independent evidence families

Crohn's DiseaseWell supported
0.75
agreement 0.610.89
Genetic95%Literature5%

Open Targets aggregate 0.46 · 2 independent evidence families

Autoimmune DiseasesModerately supported
0.73
agreement 0.590.87
Genetic97%Literature3%

Open Targets aggregate 0.45 · 2 independent evidence families

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, Rheumatoid0.48
Diabetes Mellitus, Type 10.48
Inflammatory Bowel Diseases0.46
Crohn's Disease0.46
Autoimmune Diseases0.45
Psoriasis0.44
Lupus Erythematosus, Systemic0.43
Hypothyroidism0.40
Arthritis0.39

Tractability

Small moleculesEmerging

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

AntibodiesEmerging

Feasibility evidence (go cc high conf and uniprot loc med conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

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

View underlying tractability evidence (8)
SM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of catalytic activityToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Research activity

1 papers · to 2023

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

Most cited

Recent

Europe PMC papers linked directly to this protein.