ZW10

Centromere/kinetochore protein zw10 homolog is a protein that in humans is encoded by the ZW10 gene.[5][6] This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. The encoded protein binds to centromeres during the prophase, metaphase, and early anaphase cell division stages and to kinetochore microtubules during metaphase.[6]

ZW10
Identifiers
AliasesZW10, HKNTC1AP, zw10 kinetochore protein
External IDsOMIM: 603954 MGI: 1349478 HomoloGene: 37959 GeneCards: ZW10
Orthologs
SpeciesHumanMouse
Entrez

9183

26951

Ensembl

ENSG00000086827

ENSMUSG00000032264

UniProt

O43264

O54692

RefSeq (mRNA)

NM_004724

NM_012039

RefSeq (protein)

NP_004715

NP_036169

Location (UCSC)Chr 11: 113.73 – 113.77 MbChr 9: 48.97 – 48.99 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

Zw10
Identifiers
SymbolZw10
PfamPF06248
Pfam clanCL0295
InterProIPR009361
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Zeste white 10 (ZW10) was initially identified as a mitotic checkpoint protein involved in chromosome segregation, and then implicated in targeting cytoplasmic dynein and dynactin to mitotic kinetochores, but it is also important in non-dividing cells. These include cytoplasmic dynein targeting to Golgi and other membranes, and SNARE-mediated ER-Golgi trafficking.[7][8] Dominant-negative ZW10, anti-ZW10 antibody, and ZW10 RNA interference (RNAi) cause Golgi dispersal. ZW10 RNAi also disperse endosomes and lysosomes.[8]

Drosophila kinetochore components Rough deal (Rod) and Zw10 are required for the proper functioning of the metaphase checkpoint in flies.[9] The eukaryotic spindle assembly checkpoint (SAC) monitors microtubule attachment to kinetochores and prevents anaphase onset until all kinetochores are aligned on the metaphase plate. It is an essential surveillance mechanism that ensures high fidelity chromosome segregation during mitosis. In higher eukaryotes, cytoplasmic dynein is involved in silencing the SAC by removing the checkpoint proteins Mad2 and the Rod-Zw10-Zwilch complex (RZZ) from aligned kinetochores.[10][11][12]

Interactions

ZW10 has been shown to interact with RINT1[13]

References

  1. GRCh38: Ensembl release 89: ENSG00000086827 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000032264 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Starr DA, Williams BC, Li Z, Etemad-Moghadam B, Dawe RK, Goldberg ML (Oct 1997). "Conservation of the centromere/kinetochore protein ZW10". J Cell Biol. 138 (6): 1289–301. doi:10.1083/jcb.138.6.1289. PMC 2132553. PMID 9298984.
  6. "Entrez Gene: ZW10 ZW10, kinetochore associated, homolog (Drosophila)".
  7. Vallee RB, Varma D, Dujardin DL (November 2006). "ZW10 function in mitotic checkpoint control, dynein targeting and membrane trafficking: is dynein the unifying theme?". Cell Cycle. 5 (21): 2447–51. doi:10.4161/cc.5.21.3395. PMC 2794429. PMID 17102640.
  8. Varma D, Dujardin DL, Stehman SA, Vallee RB (February 2006). "Role of the kinetochore/cell cycle checkpoint protein ZW10 in interphase cytoplasmic dynein function". J. Cell Biol. 172 (5): 655–62. doi:10.1083/jcb.200510120. PMC 2063698. PMID 16505164.
  9. Basto R, Gomes R, Karess RE (December 2000). "Rough deal and Zw10 are required for the metaphase checkpoint in Drosophila". Nat. Cell Biol. 2 (12): 939–43. doi:10.1038/35046592. PMID 11146659. S2CID 27007621.
  10. Griffis ER, Stuurman N, Vale RD (June 2007). "Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore". J. Cell Biol. 177 (6): 1005–15. doi:10.1083/jcb.200702062. PMC 2064361. PMID 17576797.
  11. Famulski JK, Vos L, Sun X, Chan G (February 2008). "Stable hZW10 kinetochore residency, mediated by hZwint-1 interaction, is essential for the mitotic checkpoint". J. Cell Biol. 180 (3): 507–20. doi:10.1083/jcb.200708021. PMC 2234252. PMID 18268100.
  12. Yang Z, Tulu US, Wadsworth P, Rieder CL (June 2007). "Kinetochore dynein is required for chromosome motion and congression independent of the spindle checkpoint". Curr. Biol. 17 (11): 973–80. doi:10.1016/j.cub.2007.04.056. PMC 2570756. PMID 17509882.
  13. Hirose H, Arasaki K, Dohmae N, Takio K, Hatsuzawa K, Nagahama M, Tani K, Yamamoto A, Tohyama M, Tagaya M (March 2004). "Implication of ZW10 in membrane trafficking between the endoplasmic reticulum and Golgi". EMBO J. 23 (6): 1267–78. doi:10.1038/sj.emboj.7600135. PMC 381410. PMID 15029241.

Further reading


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