Centromere-associated protein E (CENPE)

The protein contains 2701 amino acids for an estimated molecular weight of 316415 Da.

 

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 B (updated: Sept. 12, 2018)

Protein identification was indicated in the following studies:

  1. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  2. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 0%
Model score: 0
No model available.

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VariantDescription
MCPH13
MCPH13
dbSNP:rs2615542
dbSNP:rs35100664
dbSNP:rs1381657
dbSNP:rs2306106
dbSNP:rs2243682

The reference OMIM entry for this protein is 117143

Centromeric protein e; cenpe
Kinesin family member 10; kif10

DESCRIPTION

The CENPE gene encodes a large kinetochore-associated kinesin-like motor protein required for spindle microtubule capture and attachment at the kinetochore during cell division (summary by Mirzaa et al., 2014).

CLONING

Yen et al. (1991) identified a 250- to 300-kD human centromere-associated protein, CENPE, by preparing monoclonal antibodies against a fraction of HeLa chromosome scaffold proteins enriched for centromere/kinetochore components. In cells progressing through different parts of the cell cycle, the localization of CENPE differs markedly from that observed for the previously identified centromere proteins CENPA (117139), CENPB (117140), CENPC (117141), and CENPD (117142). In contrast to these antigens, no monoclonal antibody staining was detected during interphase, and staining first appeared at the centromere region of chromosomes during prometaphase. Microinjection of the monoclonal antibody 177, which demonstrated CENPE, into metaphase cells blocked or significantly delayed progression into anaphase, although the morphology of the spindle and the configuration of the metaphase chromosomes appeared normal in these metaphase-arrested cells. Thus, CENPE function is required for the transition from metaphase to anaphase.

MAPPING

Testa et al. (1994) used CENPE cDNA to map the human gene to chromosome 4q24-q25 by fluorescence in situ hybridization. Gross (2014) mapped the CENPE gene to chromosome 4q24 based on an alignment of the CENPE sequence (GenBank GENBANK AB209996) with the genomic sequence (GRCh38).

NOMENCLATURE

Lawrence et al. (2004) presented a standardized kinesin nomenclature based on 14 family designations. Under this system, CENPE, or KIF10, belongs to the kinesin-7 family.

GENE FUNCTION

Yen et al. (1992) identified CENPE as a kinesin-like motor protein (Mr 312,000) that accumulates in the G2 phase of the cell cycle. CENPE associates with kinetochores during congression, relocates to the spindle midzone at anaphase, and is quantitatively discarded at the end of the cell division. CENPE is probably one of the motors responsible for mammalian chromosome movement and/or spindle elongation. Wood et al. (1997) cloned the Xenopus CENPE, which shows 74% identity with the human homolog. This protein associates with Xenopus centromeres in vivo and in vitro, and is required for metaphase chromosome alignment. Addition of anti-Xenopus CENPE antibodies disrupts metaphase chromosome alignment. Wood et al. (1997) further demonstrated that Xenopus CENPE powers chromosome movement towards microtubule plus ends in vitro. These data support a model in which CENPE functions in congression to tether kinetochores to microtubule plus ends. Yao et al. (2000) investigated the function of CENPE in attachment of kinetochores to spindle microtubules, alignment of chromosomes, and checkpoint signaling, using antisense oligonucleotides to suppress its synthesis and accumulation. They showed that CENPE is essential for stable, bioriented attachment of chromosomes to spindle microtubules, for development of tension across aligned chromosomes, for stabilization of spindle poles, and for satisfying the mitotic checkpoint. Using Xenopus egg extracts, Abrieu et al. (2000) found that CENPE is required for establishing and maintaining a checkpoint that delays anaphase onset until all centromeres are correctly attached to the mitotic spindle. When CENPE function was disrupted by immunode ... More on the omim web site

Subscribe to this protein entry history

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 117143 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).