Editing Janus kinase (section)

==Structure==
[[Image:Jak domain structure.svg|thumb|485px|Domain structure of Janus kinases, JH = JAK homology domain]]
JAKs range from 120-140 [[Dalton (unit)|kDa]] in size and have seven defined regions of homology called Janus homology domains 1 to 7 (JH1-7). JH1 is the [[kinase]] domain important for the [[enzyme|enzymatic]] activity of the JAK and contains typical features of a [[tyrosine kinase]] such as conserved [[tyrosine]]s necessary for JAK activation (e.g., Y1038/Y1039 in JAK1, Y1007/Y1008 in JAK2, Y980/Y981 in JAK3, and Y1054/Y1055 in Tyk2). Phosphorylation of these dual tyrosines leads to the conformational changes in the JAK protein to facilitate binding of [[substrate (biochemistry)|substrate]].  JH2 is a [[pseudokinase domain]], a domain structurally similar to a tyrosine kinase and essential for a normal kinase activity, yet lacks enzymatic activity. This domain may be involved in regulating the activity of JH1, and was likely a duplication of the JH1 domain which has undergone mutation post-duplication.  The JH3-JH4 domains of JAKs share homology with [[Src (gene)|Src-homology]]-2 ([[SH2 domain|SH2]]) domains. The [[amino terminal]] (NH<sub>2</sub>) end (JH4-JH7) of Jaks is called a [[FERM domain]] (short for [[band 4.1]], [[ezrin]], [[radixin]] and [[moesin]]); this domain is also found in the [[focal adhesion kinase]] (FAK) family and is involved in association of JAKs with [[cytokine]] receptors and/or other kinases.<ref name="Kisselva"/>