TYK2
Function
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).
Involvement in disease
Immunodeficiency 35
IMD35
A primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated (PubMed:7638186). Phosphorylation by JAK1 at Tyr-1054 and Tyr-1055 induces kinase activation (PubMed:8232552, PubMed:8702790).
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.
Tissue Specificity
Observed in all cell lines analyzed. Expressed in a variety of lymphoid and non-lymphoid cell lines.
Alternative names
Non-receptor tyrosine-protein kinase TYK2, TYK2