Alternative titles; symbols
HGNC Approved Gene Symbol: ZWINT
Cytogenetic location: 10q21.1 Genomic coordinates (GRCh38) : 10:56,357,227-56,361,273 (from NCBI)
Using ZW10 (603954) as bait in a yeast 2-hybrid screen of a B-cell cDNA library, followed by screening a HeLa cell cDNA library, Starr et al. (2000) cloned ZWINT. The deduced 277-amino acid protein has a calculated molecular mass of 32 kD and likely assumes an extended coiled-coil conformation. Northern blot analysis detected a 1.8-kb transcript in all tumor cell lines examined. Western blot analysis of total HeLa cell lysates detected a major ZWINT protein with an apparent molecular mass of 43 kD and a minor species with an apparent molecular mass of 53 kD.
Using yeast 2-hybrid analysis, Starr et al. (2000) confirmed a direct interaction between ZWINT and ZW10. The C-terminal third of ZW10 interacted with ZWINT, but the full-length protein showed a tighter association. ZWINT was also able to self associate. In HeLa cells arrested in a metaphase-like state by the microtubule poison nocodazole, ZWINT colocalized with ZW10 at kinetochores at a position slightly outside the central part of the centromere. During interphase of cycling HeLa cells, ZWINT was uniformly distributed within the cytoplasm. At prophase, ZWINT localized to the kinetochore prior to ZW10 localization, and ZWINT remained at the kinetochore until late in anaphase. ZWINT also localized to neocentromeres and to the active centromere of dicentric chromosomes. Starr et al. (2000) hypothesized that ZWINT associates with all active centromeres and may play a role in centromere function.
Obuse et al. (2004) found that ZWINT localized to HeLa cell kinetochores during mitosis and was associated with a preformed kinetochore complex containing MIS12 (609178), DC8 (609174), C20ORF172 (609175), and HP1-alpha (CBX5; 604478). MIS12 RNA interference abolished the kinetochore localization of ZWINT, DC8, and C20ORF172.
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.
The International Radiation Hybrid Mapping Consortium mapped the ZWINT gene to chromosome 10 (STS-H99221).
Musio, A., Mariani, T., Montagna, C., Zambroni, D., Ascoli, C., Ried, T., Vezzoni, P. Recapitulation of the Roberts syndrome cellular phenotype by inhibition of INCENP, ZWINT-1 and ZW10 genes. Gene 331: 33-40, 2004. [PubMed: 15094189] [Full Text: https://doi.org/10.1016/j.gene.2004.01.028]
Obuse, C., Iwasaki, O., Kiyomitsu, T., Goshima, G., Toyoda, Y., Yanagida, M. A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Nature Cell Biol. 6: 1135-1141, 2004. [PubMed: 15502821] [Full Text: https://doi.org/10.1038/ncb1187]
Starr, D. A., Saffery, R., Li, Z., Simpson, A. E., Choo, K. H. A., Yen, T. J., Goldberg, M. L. HZwint-1, a novel human kinetochore component that interacts with HZW10. J. Cell Sci. 113: 1939-1950, 2000. [PubMed: 10806105] [Full Text: https://doi.org/10.1242/jcs.113.11.1939]