Recombinant Human Non-receptor tyrosine-protein kinase TYK2 (TYK2), partial

Function

Non-membrane spanning protein tyrosine kinase 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). Involved in the oncostatin-M-mediated signaling pathway through both type I OSM receptor complex (heterodimers composed of LIFR and IL6ST) and type II OSM receptor complex (heterodimers composed of OSMR and IL6ST) (PubMed:9188471)

Disease Association

Immunodeficiency 35 (IMD35) : A primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Observed in all cell lines analyzed. Expressed in a variety of lymphoid and non-lymphoid cell lines

Subunit

(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

• Firmbach-Kraft I. et al. TYK2, prototype of a novel class of non-receptor tyrosine kinase genes. — Oncogene (1990)
• PubMed: CI-2Q518BA3CL950 (FEB-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Velazquez L. et al. A protein tyrosine kinase in the interferon alpha/beta signaling pathway. — Cell (1992)
• Krolewski J.J. et al. Identification and chromosomal mapping of new human tyrosine kinase genes. — Oncogene (1990)
• Partanen J. et al. Putative tyrosine kinases expressed in K-562 human leukemia cells. — Proc. Natl. Acad. Sci. U.S.A. (1990)
• Mueller M. et al. The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction. — Nature (1993)
• Abramovich C. et al. Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN-alpha and IFN-beta. — EMBO J. (1994)