View source for Kinase Subfamily NEK1

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[[kinase classification|Kinase Classification]]: [[Kinase_Group_Other|Group Other]]: [[Kinase_Family_NEK|Family NEK]]: [[Kinase_Subfamily_NEK1|Subfamily NEK1]]

====Evolution====
NEK1 is widespread in eukaryotes, though lost in fungi, Drosophila, and C. elegans, correlated with their loss of primary cilium genes. Most species have a single NEK1. Vertebrates have 3 members, NEK1, NEK3, and NEK5, with additional duplications in fish.

====Domain Structure====
All have an N-terminal kinase domain with varied C-terminal extensions that typically are poorly conserved, though annotated to have coiled-coil and PEST regions and having some sequence conservation between the three proteins. The three vertebrate members have distinctly different lengths, from 500-1200 AA. Invertebrate members are closest to the long form, NEK1, with several conserved regions, indicating that NEK3 and NEK5 are truncated forms.

====Functions====

NEK3 is the least studied member of the subfamily, and has no known association with cell cycle or DNA damage <cite>Tanaka</cite>. It functions downstream of prolactin signaling in breast tissue, which induces phosphorylation on T165 via the Erk pathway. This activation causes cytoskeletal changes that promote migration and invasion <cite>Harrington</cite>, including a direct interaction and phosphorylation of paxillin, and upregulation of Rac1 <cite>Miller</cite>. Prolactin induces an interaction between NEK3 and the VAV2/VAV3 guanine nucleotide exchange factors, and between them and the prolactin receptor <cite>Miller2</cite>. NEK3 was also reported to phosphorylate SNAP29, a t-SNARE protein, on S105, and cause its membrane association <cite>Rapaport</cite>


====References====
<biblio>
#Tanaka pmid=10224116
#Harrington pmid=27489110
#Miller pmid=17297458
#Miller2 pmid=15618286
#Rapaport pmid=29454964
</biblio>