CENPE

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]

Full Name

Centromere Protein E

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).

Biological Process

Antigen processing and presentation of exogenous peptide antigen via MHC class II Source: Reactome
Attachment of mitotic spindle microtubules to kinetochore Source: UniProtKB
Cell division Source: UniProtKB-KW
Chromosome segregation Source: UniProtKB
Kinetochore assembly Source: UniProtKB
Lateral attachment of mitotic spindle microtubules to kinetochore Source: UniProtKB
Metaphase plate congression Source: UniProtKB
Microtubule-based movement Source: GO_Central
Microtubule plus-end directed mitotic chromosome migration Source: UniProtKB
Mitotic cell cycle Source: UniProtKB
Mitotic chromosome movement towards spindle pole Source: UniProtKB
Mitotic metaphase plate congression Source: UniProtKB
Mitotic spindle organization Source: UniProtKB
Multicellular organism development Source: UniProtKB-KW
Positive regulation of protein kinase activity Source: UniProtKB
Regulation of mitotic metaphase/anaphase transition Source: UniProtKB
Retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum Source: Reactome

Cellular Location

Spindle; Kinetochore; 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).

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.

PTM

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.