Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity (PubMed:10542297, PubMed:10995743, PubMed:7657660, PubMed:7813427, PubMed:8232552). Plays both structural and catalytic roles in numerous interleukins and interferons (IFN-alpha/beta) signaling (PubMed:10542297). Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 (PubMed:10542297, PubMed:7638186).
The heterodimeric cytokine receptor complexes are composed of (1) a TYK2-associated receptor chain (IFNAR1, IL12RB1, IL10RB or IL13RA1), and (2) a second receptor chain associated either with JAK1 or JAK2 (PubMed:10542297, PubMed:25762719, PubMed:7526154, PubMed:7813427). In response to cytokine-binding to receptors, phosphorylates and activates receptors (IFNAR1, IL12RB1, IL10RB or IL13RA1), creating docking sites for STAT members (PubMed:7526154, PubMed:7657660). In turn, recruited STATs are phosphorylated by TYK2 (or JAK1/JAK2 on the second receptor chain), form homo- and heterodimers, translocate to the nucleus, and regulate cytokine/growth factor responsive genes (PubMed:10542297, PubMed:25762719, PubMed:7657660).
Negatively regulates STAT3 activity by promototing phosphorylation at a specific tyrosine that differs from the site used for signaling (PubMed:29162862)
Interacts (via FERM domain) with JAKMIP1 (PubMed:15277531, PubMed:20478313). Interacts with PIK3R1; this interaction is important for cell migration (PubMed:10995743). Interacts with MPL/TPOR (PubMed:15899890)
(Microbial infection) Interacts with Epstein-Barr virus protein LMP1; this interaction inhibits TYK2-mediated interferon signaling
(Microbial infection) Interacts with papillomavirus-18 protein E6; this interaction impairs JAK-STAT activation by interferon-alpha
(Microbial infection) Interacts with Epstein-Barr virus (EBV) tegument protein BGLF2; this interaction participates in the inhibition of type I IFN signaling by the virus
Observed in all cell lines analyzed. Expressed in a variety of lymphoid and non-lymphoid cell lines
A primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE.
Click a pathway to open the interactive Reactome viewer.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to TYK2, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 7
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT06281106 | Psoriasis | TYK2 Inhibition in Paradoxical Psoriasis | PHASE2, PHASE3 | TERMINATED |
| NCT05437263 | Dermatomyositis | A Study to Investigate the Efficacy and Safety of Brepocitinib in Adults With Dermatomyositis | PHASE3 | ACTIVE_NOT_RECRUITING |
| NCT04179656 | Solid Tumor, HER2 Gene Mutation, HER-2 Gene Amplification, HER-2 Protein Overexpression | The Basket Study of Pyrotinib Maleate for HER2-Postive Solid Tumor | PHASE2 | UNKNOWN |
| NCT03601819 | Lymphoma, T-Cell, Cutaneous, Lymphoma, T-Cell, Peripheral, Chronic Lymphocytic Leukemia, Lymphoproliferative Disorders, Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma, Mantle Cell Lymphoma | Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders | PHASE1 | TERMINATED |
| NCT05655299 | Psoriasis | VTX958 Versus Placebo for the Treatment of Moderate to Severe Psoriasis | PHASE2 | TERMINATED |
| NCT05688852 | Crohn Disease | VTX958 for the Treatment of Moderately to Severely Active Crohn's Disease | PHASE2 | TERMINATED |
| NCT05076006 | Cicatricial Alopecia | Dual JAK1/TYK2 Inhibitor for Cicatricial Alopecia | PHASE2 | COMPLETED |
| NCT06506591 | Healthy Participants | A Single-And Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of WD-890 Tablets in Healthy Chinese Subjects | PHASE1 | COMPLETED |
| NCT07234591 | Plaque Psoriasis, Moderate to Severe Plaque Psoriasis | A Study to Evaluate Effectiveness and Safety of a TYK2 Inhibitor in Subjects With Moderate to Severe Plaque Psoriasis | NA | RECRUITING |
| NCT05730725 | Psoriasis | A Study to Evaluate Effectiveness and Safety of BMS-986322 in Participants With Moderate-to-Severe Psoriasis | PHASE2 | COMPLETED |