Structural highlights
Disease
[TYK2_HUMAN] Mendelian susceptibility to mycobacterial diseases;Autosomal recessive hyper IgE syndrome. Defects in TYK2 are the cause of protein-tyrosine kinase 2 deficiency (TYK2 deficiency) [MIM:611521]; also known as autosomal recessive hyper-IgE syndrome (HIES) with atypical mycobacteriosis. TYK2 deficiency consists of a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE.
Function
[TYK2_HUMAN] Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.[1]
Publication Abstract from PubMed
Members of the JAK family of protein kinases mediate signal transduction from cytokine receptors to transcription factor activation. Over-stimulation of these pathways is causative in immune disorders like rheumatoid arthritis, psoriasis, lupus, and Crohn's disease. A search for selective inhibitors of a JAK kinase has led to our characterization of a previously unknown kinase conformation arising from presentation of Tyr962 of TYK2 to an inhibitory small molecule via an H-bonding interaction. A small minority of protein kinase domains has a Tyrosine residue in this position within the alphaC-beta4 loop, and it is the only amino acid commonly seen here with H-bonding potential. These discoveries will aid design of inhibitors that discriminate among the JAK family and more widely among protein kinases. Proteins 2010. (c) 2010 Wiley-Liss, Inc.
A new regulatory switch in a JAK protein kinase.,Tsui V, Gibbons P, Ultsch M, Mortara K, Chang C, Blair W, Pulk R, Stanley M, Starovasnik M, Williams D, Lamers M, Leonard P, Magnuson S, Liang J, Eigenbrot C Proteins. 2010 Oct 7. PMID:21117080[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Colamonici O, Yan H, Domanski P, Handa R, Smalley D, Mullersman J, Witte M, Krishnan K, Krolewski J. Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase. Mol Cell Biol. 1994 Dec;14(12):8133-42. PMID:7526154
- ↑ Tsui V, Gibbons P, Ultsch M, Mortara K, Chang C, Blair W, Pulk R, Stanley M, Starovasnik M, Williams D, Lamers M, Leonard P, Magnuson S, Liang J, Eigenbrot C. A new regulatory switch in a JAK protein kinase. Proteins. 2010 Oct 7. PMID:21117080 doi:10.1002/prot.22889
