Centromere/kinetochore protein zw10 homolog (ZW10)

The protein contains 779 amino acids for an estimated molecular weight of 88829 Da.

 

Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex (PubMed:11590237, PubMed:15485811, PubMed:15824131). Involved in regulation of membrane traffic between the Golgi and the endoplasmic reticulum (ER); the function is proposed to depend on its association in the interphase NRZ complex which is believed to play a role in SNARE assembly at the ER (PubMed:15029241). (updated: Oct. 25, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 0%
Model score: 39
MODL_ROSETTA-3.4

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VariantDescription
dbSNP:rs2271796

The reference OMIM entry for this protein is 603954

Zeste-white 10, drosophila, homolog of; zw10

CLONING

Mutations in the Drosophila zeste-white 10 (zw10) gene disrupt chromosome segregation, producing chromosomes that lag at the metaphase plate during anaphase of mitosis and both meiotic divisions. During the cell cycle, the Drosophila zw10 protein moves from the centromere/kinetochore at prometaphase to kinetochore microtubules at metaphase, and then back to the centromere/kinetochore at anaphase. Starr et al. (1997) suggested that zw10 may act at the kinetochore as part of a tension-sensing checkpoint that renders anaphase onset dependent upon bipolar tension exerted across all centromeres. By screening an EST database, they identified cDNAs encoding zw10 homologs in organisms with divergent centromere structures, including human, C. elegans, and Arabidopsis. Overall, the predicted ZW10 proteins of Drosophila, C. elegans, human, and Arabidopsis share 17 to 26% identity. Northern blot analysis revealed that the human ZW10 gene was expressed as an approximately 2.9-kb mRNA in various human cell lines. On Western blots of HeLa cell extracts, the deduced 779-amino acid human ZW10 protein migrated as a doublet of approximately 90 kD. Using immunofluorescence, the authors determined that ZW10 displayed a dynamic pattern of localization during the HeLa cell cycle, similar to that observed for Drosophila zw10.

GENE FUNCTION

Starr et al. (1997) found that injection of antisense C. elegans zw10 RNA into nematode gonads caused cell division disruptions similar to those seen in Drosophila zw10 mutants. They concluded that at least some aspects of the functional role of the ZW10 protein in ensuring proper chromosome segregation are conserved in higher eukaryotes. By coimmunoprecipitation of HeLa cells, Chan et al. (2000) and Scaerou et al. (2001) determined that KNTC1 (607363) interacts with ZW10. Using a yeast 2-hybrid screen, Scaerou et al. (2001) localized the ZW10-binding region to the middle third of KNTC1. By immunofluorescent localization in synchronized HeLa cells, Scaerou et al. (2001) found KNTC1 and ZW10 colocalized at kinetochores during prometaphase and metaphase, with the brightest staining for both proteins on the spindle near the poles. After late anaphase and telophase, ZW10 accumulated at the spindle midzone, while KNTC1 staining became prominent at the spindle poles. By injection of antibodies directed toward KNTC1 or ZW10 into HeLa cells shortly after their release from the G1/S boundary, Chan et al. (2000) found that anaphase cells contained lagging chromosomes and divided cells contained chromatin bridges. They concluded that both KNTC1 and ZW10 are essential components of the mitotic checkpoint. Using yeast 2-hybrid analysis, Starr et al. (2000) demonstrated a direct interaction between ZWINT (609177) and ZW10. The C-terminal third of ZW10 interacted with ZWINT, but the full-length protein showed a tighter association. At prophase, ZWINT localized to the kinetochore prior to ZW10 localization. Starr et al. (2000) hypothesized that ZWINT may play a role in targeting ZW10 to the kinetochore at prometaphase. Musio et al. (2004) found that inhibition of INCENP (604411), ZWINT, and ZW10 with antisense oligonucleotides resulted in the appearance of mitotic cells characterized by centromere separation, chromosome aneuploidy, and micronuclei formation. The chromosome morphology was similar to that of Roberts syndrome (268300) chromosomes when analyzed by atomic force microscopy.

MAPPING

The Int ... More on the omim web site

Subscribe to this protein entry history

Dec. 10, 2018: Protein entry updated
Automatic update: model status changed

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603954 was added.