TYK2
This gene encodes a member of the tyrosine kinase and, more specifically, the Janus kinases (JAKs) protein families. This protein associates with the cytoplasmic domain of type I and type II cytokine receptors and promulgate cytokine signals by phosphorylating receptor subunits. It is also component of both the type I and type III interferon signaling pathways. As such, it may play a role in anti-viral immunity. A mutation in this gene has been associated with hyperimmunoglobulin E syndrome (HIES) - a primary immunodeficiency characterized by elevated serum immunoglobulin E. [provided by RefSeq, Jul 2008]
Full Name
TYK2 Gene(Protein Coding) Tyrosine Kinase 2
Function
Non-receptor kinase involved in various processes including cell growth, development, cell migration, innate and adaptive immunity (PubMed:10995743, PubMed:10542297).
Plays both structural and catalytic roles in numerous cytokines and interferons signaling (PubMed:10542297).
Associates with cytokine and growth factor receptors and activate STAT family members including STAT1, STAT3, STAT4 or STAT6 (PubMed:10542297, PubMed:7638186).
The heterodimeric cytokine receptor complexes are composed of a TYK2-associated receptor chain (IFNAR1, IL12RB1, IL10RB or IL13RA1) which serves as the signal transducing chain harboring STAT docking sites once phosphorylated by TYK2, and a second receptor chain associated either with JAK1 or JAK2 (PubMed:10542297, PubMed:7526154, PubMed:25762719).
In turn, recruited STATs are phosphorylated, form homo- and heterodimers, translocate to the nucleus, and regulate cytokine/growth factor responsive genes. Negatively regulates STAT3 activity by promototing phosphorylation at a specific tyrosine that differs from the site used for signaling (PubMed:29162862).
Biological Process
Cellular response to virus1 PublicationIC:ComplexPortal
Cytokine-mediated signaling pathwayTAS:Reactome
Immune response1 PublicationIC:ComplexPortal
Intracellular signal transductionIEA:InterPro
Positive regulation of interferon-gamma productionManual Assertion Based On ExperimentIDA:ComplexPortal
Positive regulation of interleukin-17 production1 PublicationIC:ComplexPortal
Positive regulation of natural killer cell proliferationManual Assertion Based On ExperimentIDA:ComplexPortal
Positive regulation of NK T cell proliferationManual Assertion Based On ExperimentIDA:ComplexPortal
Positive regulation of receptor signaling pathway via JAK-STATManual Assertion Based On ExperimentIDA:ComplexPortal
Positive regulation of T cell proliferationManual Assertion Based On ExperimentIDA:ComplexPortal
Positive regulation of T-helper 17 type immune response1 PublicationIC:ComplexPortal
Protein phosphorylationManual Assertion Based On ExperimentTAS:ProtInc
Type I interferon signaling pathwayTAS:Reactome
Type III interferon signaling pathway1 PublicationIC:ComplexPortal
Cellular Location
cytoplasm
cytoskeleton
cytosol
extracellular exosome
interleukin-12 receptor complex
interleukin-23 receptor complex
nucleus
plasma membrane
Involvement in disease
Immunodeficiency 35 (IMD35):
A primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE.
PTM
Phosphorylated (PubMed:7638186).
Phosphorylations at Tyr-1054 and Tyr-1055 induce kinase activation (PubMed:8702790).