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CENPE

Domain

The protein is composed of a N-terminal kinesin-motor domain involved in the chromosome movements, a long coil-coiled region involved in the homodimerization and an inhibitory C-tail involved in autoinhibition of the N-terminal catalytic part.

Function

Microtubule plus-end-directed kinetochore motor which plays an important role in chromosome congression, microtubule-kinetochore conjugation and spindle assembly checkpoint activation. Drives chromosome congression (alignment of chromosomes at the spindle equator resulting in the formation of the metaphase plate) by mediating the lateral sliding of polar chromosomes along spindle microtubules towards the spindle equator and by aiding the establishment and maintenance of connections between kinetochores and spindle microtubules (PubMed:7889940, PubMed:23891108, PubMed:25395579). The transport of pole-proximal chromosomes towards the spindle equator is favored by microtubule tracks that are detyrosinated (PubMed:25908662). Acts as a processive bi-directional tracker of dynamic microtubule tips; after chromosomes have congressed, continues to play an active role at kinetochores, enhancing their links with dynamic microtubule ends (PubMed:23955301). Suppresses chromosome congression in NDC80-depleted cells and contributes positively to congression only when microtubules are stabilized (PubMed:25743205). Plays an important role in the formation of stable attachments between kinetochores and spindle microtubules (PubMed:17535814) The stabilization of kinetochore-microtubule attachment also requires CENPE-dependent localization of other proteins to the kinetochore including BUB1B, MAD1 and MAD2. Plays a role in spindle assembly checkpoint activation (SAC) via its interaction with BUB1B resulting in the activation of its kinase activity, which is important for activating SAC. Necessary for the mitotic checkpoint signal at individual kinetochores to prevent aneuploidy due to single chromosome loss (By similarity).

Involvement in disease

Microcephaly 13, primary, autosomal recessive

MCPH13

A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

The C-terminal inhibitory domain is phosphorylated. Phosphorylation relieves autoinhibition of the kinetochore motor (By similarity).

Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the association to the kinetochore.

Sequence similarities

Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.

Cellular localization

  • Chromosome
  • Centromere
  • Kinetochore
  • Cytoplasm
  • Cytoskeleton
  • Spindle
  • Chromosome
  • Centromere
  • Associates with kinetochores during congression (as early as prometaphase), relocates to the spindle midzone at anaphase, and is quantitatively discarded at the end of the cell division (By similarity). Recruited to the kinetochore in a SEPT7, CENPQ and TRAPPC12-dependent manner (PubMed:18460473, PubMed:25918224, PubMed:25395579). Recruited to the pericentromeric/centromeric regions of the chromosome in a CTCF-dependent manner (PubMed:26321640).

Alternative names

  • Centromere-associated protein E
  • Centromere protein E
  • Kinesin-7
  • Kinesin-related protein CENPE
  • CENP-E
  • CENPE

Target type

Proteins

Primary research area

Epigenetics

Molecular weight

316415Da