ZW10

Zw10 kinetochore protein
Identifiers
Symbols	ZW10 ; HZW10; KNTC1AP
External IDs	OMIM: 603954 MGI: 1349478 HomoloGene: 37959 GeneCards: ZW10 Gene
Gene ontology Molecular function • protein binding • centromeric DNA binding Cellular component • kinetochore • condensed chromosome kinetochore • spindle pole • nucleus • cytoplasm • endoplasmic reticulum • endoplasmic reticulum membrane • kinetochore microtubule • cytosol • membrane • Dsl1p complex • RZZ complex Biological process • mitotic sister chromatid segregation • establishment of mitotic spindle orientation • mitotic cell cycle • protein complex assembly • ER to Golgi vesicle-mediated transport • Golgi organization • mitotic metaphase plate congression • mitotic cell cycle checkpoint • regulation of exit from mitosis • meiotic nuclear division • small GTPase mediated signal transduction • protein transport • protein localization to kinetochore • cell division Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
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 Mb	Chr 9: 49.06 – 49.08 Mb
PubMed search

Centromere/kinetochore protein zw10 homolog is a protein that in humans is encoded by the ZW10 gene.^[1][2] 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.^[2]

Function

Zw10 Identifiers Symbol Zw10 Pfam PF06248 Pfam clan CL0295 InterPro IPR009361 Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure 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.^[3][4] Dominant-negative ZW10, anti-ZW10 antibody, and ZW10 RNA interference (RNAi) cause Golgi dispersal. ZW10 RNAi also disperse endosomes and lysosomes.^[4]

Drosophila kinetochore components Rough deal (Rod) and Zw10 are required for the proper functioning of the metaphase checkpoint in flies.^[5] 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.^[6][7][8]

Interactions

ZW10 has been shown to interact with RINT1^[9]

References

1. 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.
2. "Entrez Gene: ZW10 ZW10, kinetochore associated, homolog (Drosophila)".
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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

• Starr DA, Williams BC, Hays TS, Goldberg ML (1998). "ZW10 helps recruit dynactin and dynein to the kinetochore.". J. Cell Biol. 142 (3): 763–74. doi:10.1083/jcb.142.3.763. PMC 2148168. PMID 9700164.
• Starr DA, Saffery R, Li Z, et al. (2000). "HZwint-1, a novel human kinetochore component that interacts with HZW10.". J. Cell. Sci. 113 (11): 1939–50. PMID 10806105.
• Chan GK, Jablonski SA, Starr DA, et al. (2001). "Human Zw10 and ROD are mitotic checkpoint proteins that bind to kinetochores.". Nat. Cell Biol. 2 (12): 944–7. doi:10.1038/35046598. PMID 11146660.
• Scaërou F, Starr DA, Piano F, et al. (2001). "The ZW10 and Rough Deal checkpoint proteins function together in a large, evolutionarily conserved complex targeted to the kinetochore.". J. Cell. Sci. 114 (Pt 17): 3103–14. PMID 11590237.
• Gevaert K, Goethals M, Martens L, et al. (2004). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.". Nat. Biotechnol. 21 (5): 566–9. doi:10.1038/nbt810. PMID 12665801.
• Hirose H, Arasaki K, Dohmae N, et al. (2005). "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.
• Musio A, Mariani T, Montagna C, et al. (2004). "Recapitulation of the Roberts syndrome cellular phenotype by inhibition of INCENP, ZWINT-1 and ZW10 genes.". Gene 331: 33–40. doi:10.1016/j.gene.2004.01.028. PMID 15094189.
• Nakajima K, Hirose H, Taniguchi M, et al. (2005). "Involvement of BNIP1 in apoptosis and endoplasmic reticulum membrane fusion.". EMBO J. 23 (16): 3216–26. doi:10.1038/sj.emboj.7600333. PMC 514507. PMID 15272311.
• Wang H, Hu X, Ding X, et al. (2005). "Human Zwint-1 specifies localization of Zeste White 10 to kinetochores and is essential for mitotic checkpoint signaling.". J. Biol. Chem. 279 (52): 54590–8. doi:10.1074/jbc.M407588200. PMID 15485811.
• Kops GJ, Kim Y, Weaver BA, et al. (2005). "ZW10 links mitotic checkpoint signaling to the structural kinetochore.". J. Cell Biol. 169 (1): 49–60. doi:10.1083/jcb.200411118. PMC 1351127. PMID 15824131.
• Varma D, Dujardin DL, Stehman SA, Vallee RB (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.
• Nousiainen M, Silljé HH, Sauer G, et al. (2006). "Phosphoproteome analysis of the human mitotic spindle.". Proc. Natl. Acad. Sci. U.S.A. 103 (14): 5391–6. doi:10.1073/pnas.0507066103. PMC 1459365. PMID 16565220.
• Arasaki K, Taniguchi M, Tani K, Tagaya M (2006). "RINT-1 regulates the localization and entry of ZW10 to the syntaxin 18 complex.". Mol. Biol. Cell 17 (6): 2780–8. doi:10.1091/mbc.E05-10-0973. PMC 1474792. PMID 16571679.
• Lin YT, Chen Y, Wu G, Lee WH (2006). "Hec1 sequentially recruits Zwint-1 and ZW10 to kinetochores for faithful chromosome segregation and spindle checkpoint control.". Oncogene 25 (52): 6901–14. doi:10.1038/sj.onc.1209687. PMID 16732327.
• Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry.". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
• Arasaki K, Uemura T, Tani K, Tagaya M (2007). "Correlation of Golgi localization of ZW10 and centrosomal accumulation of dynactin.". Biochem. Biophys. Res. Commun. 359 (3): 811–6. doi:10.1016/j.bbrc.2007.05.188. PMID 17560939.
• Sun Y, Shestakova A, Hunt L, et al. (2007). "Rab6 regulates both ZW10/RINT-1 and conserved oligomeric Golgi complex-dependent Golgi trafficking and homeostasis.". Mol. Biol. Cell 18 (10): 4129–42. doi:10.1091/mbc.E07-01-0080. PMC 1995728. PMID 17699596.