CENP-E (4q24), KIF10, MCPH13, PPP1R61.

https://www.ncbi.nlm.nih.gov/gene/1062

Official Symbol

CENPE

centromere protein E

Also known as

KIF10; CENP-E; MCPH13; PPP1R61

Summary

Centrosome-associated protein E (CENPE) is a kinesin-like motor protein that accumulates in the G2 phase of the cell cycle. Unlike other centrosome-associated proteins, it is not present during interphase and first appears at the centromere region of chromosomes during prometaphase. This protein is required for stable spindle microtubule capture at kinetochores which is a necessary step in chromosome alignment during prometaphase. This protein also couples chromosome position to microtubule depolymerizing activity. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Nov 2014]

Expression

Broad expression in bone marrow (RPKM 3.4), lymph node (RPKM 3.3) and 18 other tissues See more

Orthologs

 

Select item 3120138211.

BubR1 phosphorylates CENP-E as a switch enabling the transition from lateral association to end-on capture of spindle microtubules.

Huang Y, Lin L, Liu X, Ye S, Yao PY, Wang W, Yang F, Gao X, Li J, Zhang Y, Zhang J, Yang Z, Liu X, Yang Z, Zang J, Teng M, Wang Z, Ruan K, Ding X, Li L, Cleveland DW, Zhang R, Yao X.

Cell Res. 2019 Jul;29(7):562-578. doi: 10.1038/s41422-019-0178-z. Epub 2019 Jun 14.

Error-free mitosis depends on accurate chromosome attachment to spindle microtubules, powered congression of those chromosomes, their segregation in anaphase, and assembly of a spindle midzone at mitotic exit. The centromere-associated kinesin motor CENP-E, whose binding partner is BubR1, has been implicated in congression of misaligned chromosomes and the transition from lateral kinetochore-microtubule association to end-on capture. Although previously proposed to be a pseudokinase, here we report the structure of the kinase domain of Drosophila melanogaster BubR1, revealing its folding into a conformation predicted to be catalytically active. BubR1 is shown to be a bona fide kinase whose phosphorylation of CENP-E switches it from a laterally attached microtubule motor to a plus-end microtubule tip tracker. Computational modeling is used to identify bubristatin as a selective BubR1 kinase antagonist that targets the αN1 helix of N-terminal extension and αC helix of the BubR1 kinase domain. Inhibition of CENP-E phosphorylation is shown to prevent proper microtubule capture at kinetochores and, surprisingly, proper assembly of the central spindle at mitotic exit. Thus, BubR1-mediated CENP-E phosphorylation produces a temporal switch that enables transition from lateral to end-on microtubule capture and organization of microtubules into stable midzone arrays.

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