View source for Kinase Subfamily NEK8

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[[kinase classification|Kinase Classification]]: [[Kinase_Group_Other|Group Other]]: [[Kinase_Family_NEK|Family NEK]]: [[Kinase_Subfamily_NEK8|Subfamily NEK8]]

Editing in progress!


====Evolution====
NEK8 is found in most holozoans (animals + choanoflagellates). It has a single copy in mammals (NEK8) and Drosophila (CG10951) but has duplicated in C. elegans (nekl-1/ZC581.1, nekl-2/Y39G10AR.4), sea urchin, sponge and elsewhere.

====Domain Structure====
Like [[Kinase_Subamily_NEK9|NEK9]], members have an N-terminal kinase domain followed by a set of 7 RCC1 (regulator of chromosome condensation) domains. Many invertebrates have an additional N-terminal domain that is lost in bony vertebrates.

====Functions====
NEK8 has chromosomal and cilium functions, like many other NEKs. Human NEK8 mutations are associated with cardiac, renal and liver defects <cite>Hassan, Rajagopalan</cite>. NEK8 is associated with centrosomes in dividing cells and with the proximal cilium in non-diving cells <cite>Zalli</cite>, both of which require kinase activity and the RCC1 domain. Once cilia are formed, NEK8 is degraded by the proteasome, probably through binding of  pVHL  <cite>Ding</cite>

NEK8 is phosphorylated on the activation loop, T162, and mutations to this site increase or decrease activity, as expected <cite>Zalli</cite>


====References====
<biblio>
#Hassan pmid=31633649
#Rajagopalan pmid=26697755
#Zalli pmid=22106379
#Ding pmid=30333866
</biblio>