Kinase Family NEK

Kinase Classification: Group Other: Family NEK

Nek is a large family of kinases with multiple conserved subfamilies. Neks are widespread throughout eukaryotes, with several subfamilies emerging in fungi or metazoa

NEK1

Includes Human NEK1, NEK3, and NEK5. Found in most eukaryotes, but lost in fungi, Drosophila and C. elegans, a pattern that correlates with their loss of the xxx cilium???

NEK2

Found in fungi, animals and Dictyostelium. All have an N-terminal kinase domain and C-terminal extension. Includes the Aspergillus nimA after which the family is named.

NEK6

Includes human NEK6 and NEK7

Evolution

Bub1 is found in most eukaryotes, and has a key role in cell cycle

Domain Structure

The ancestral state of Bub1 has an N-terminal KEN box, followed by TPR repeats and a GLEBS domain, and finally a C-terminal kinase domain. In at least 9 different evolutionary lineages, Bub1 has duplicated, with one copy typically losing the kinase domain (often called MAD3) and the other losing the KEN box [1]. In vertebrates, the MAD3 homolog is BUB1, and retains the kinase domain, though it appears to be a pseudokinase.

Function

Bub1 is a mitotic checkpoint kinase with functions in the establishment of the mitotic spindle assembly checkpoint (SAC) and chromosome congression (see Wikipedia).

References

1. Suijkerbuijk SJ, van Dam TJ, Karagöz GE, von Castelmur E, Hubner NC, Duarte AM, Vleugel M, Perrakis A, Rüdiger SG, Snel B, and Kops GJ. The vertebrate mitotic checkpoint protein BUBR1 is an unusual pseudokinase. Dev Cell. 2012 Jun 12;22(6):1321-9. DOI:10.1016/j.devcel.2012.03.009 |