CENPH

Last updated
CENPH
Identifiers
Aliases CENPH , centromere protein H
External IDs OMIM: 605607; MGI: 1349448; HomoloGene: 32519; GeneCards: CENPH; OMA:CENPH - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_022909

NM_021886

RefSeq (protein)

NP_075060

NP_068686
NP_001386457

Location (UCSC) Chr 5: 69.19 – 69.21 Mb Chr 13: 100.76 – 100.78 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
CENP-H
Identifiers
SymbolCENP-H
Pfam PF05837
InterPro IPR008426
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Centromere protein H is a protein that in humans is encoded by the CENPH gene. [5] [6] [7] It is involved in the assembly of kinetochore proteins, mitotic progression and chromosome segregation. [8] [9]

Contents

Function

Centromere and kinetochore proteins play a critical role in centromere structure, kinetochore formation, and sister chromatid separation. The protein encoded by this gene colocalizes with inner kinetochore plate proteins CENP-A and CENP-C in both interphase and metaphase. CENP-H is required for the localisation of CENP-C, but not CENP-A, to the centromere. However, it may be involved in the incorporation of newly synthesised CENP-A into centromeres via its interaction with the CENP-A/CENP-HI complex. [10] CENP-H localizes outside of centromeric heterochromatin, where CENP-B is localized, and inside the kinetochore corona, where CENP-E is localized during prometaphase. It is thought that this protein can bind to itself, as well as to CENP-A, CENP-B or CENP-C. Multimers of the protein localize constitutively to the inner kinetochore plate and play an important role in the organization and function of the active centromere-kinetochore complex. [11] CENP-H contains a coiled-coil structure and a nuclear localisation signal. [11]

Studies show that CENP-H may be associated with certain human cancers. [12] [13]

CENP-H shows sequence similarity to the Schizosaccharomyces pombe kinetochore protein Fta3 which is a subunit of the Sim4 complex. This complex is required for loading the DASH complex onto the kinetochore via interaction with dad1. Fta2, Fta3 and Fta4 associate with the central core and inner repeat region of the centromere. [14]

Interactions

CENPH has also been shown to interact with KIAA0090. [15] The significance of this interaction is unclear.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000153044 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000045273 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. Sugata N, Li S, Earnshaw WC, Yen TJ, Yoda K, Masumoto H, et al. (November 2000). "Human CENP-H multimers colocalize with CENP-A and CENP-C at active centromere--kinetochore complexes". Human Molecular Genetics. 9 (19): 2919–2926. doi: 10.1093/hmg/9.19.2919 . PMID   11092768.
  6. Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M (November 2004). "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1". Nature Cell Biology. 6 (11): 1135–1141. doi:10.1038/ncb1187. PMID   15502821. S2CID   39408000.
  7. "Entrez Gene: CENPH centromere protein H".
  8. McClelland SE, Borusu S, Amaro AC, Winter JR, Belwal M, McAinsh AD, Meraldi P (December 2007). "The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity". The EMBO Journal. 26 (24): 5033–5047. doi:10.1038/sj.emboj.7601927. PMC   2140114 . PMID   18007590.
  9. Orthaus S, Ohndorf S, Diekmann S (September 2006). "RNAi knockdown of human kinetochore protein CENP-H". Biochemical and Biophysical Research Communications. 348 (1): 36–46. doi:10.1016/j.bbrc.2006.06.187. PMID   16875666.
  10. Fukagawa T, Mikami Y, Nishihashi A, Regnier V, Haraguchi T, Hiraoka Y, et al. (August 2001). "CENP-H, a constitutive centromere component, is required for centromere targeting of CENP-C in vertebrate cells". The EMBO Journal. 20 (16): 4603–4617. doi:10.1093/emboj/20.16.4603. PMC   125570 . PMID   11500386.
  11. 1 2 Sugata N, Munekata E, Todokoro K (September 1999). "Characterization of a novel kinetochore protein, CENP-H". The Journal of Biological Chemistry. 274 (39): 27343–27346. doi: 10.1074/jbc.274.39.27343 . PMID   10488063.
  12. Guo XZ, Zhang G, Wang JY, Liu WL, Wang F, Dong JQ, et al. (August 2008). "Prognostic relevance of Centromere protein H expression in esophageal carcinoma". BMC Cancer. 8: 233. doi: 10.1186/1471-2407-8-233 . PMC   2535782 . PMID   18700042.
  13. Liao WT, Song LB, Zhang HZ, Zhang X, Zhang L, Liu WL, et al. (January 2007). "Centromere protein H is a novel prognostic marker for nasopharyngeal carcinoma progression and overall patient survival". Clinical Cancer Research. 13 (2 Pt 1): 508–514. doi:10.1158/1078-0432.CCR-06-1512. PMID   17255272. S2CID   474452.
  14. Liu X, McLeod I, Anderson S, Yates JR, He X (August 2005). "Molecular analysis of kinetochore architecture in fission yeast". The EMBO Journal. 24 (16): 2919–2930. doi:10.1038/sj.emboj.7600762. PMC   1187945 . PMID   16079914.
  15. Prieto C, De Las Rivas J (July 2006). "APID: Agile Protein Interaction DataAnalyzer". Nucleic Acids Research. 34 (Web Server issue): W298 –W302. doi:10.1093/nar/gkl128. PMC   1538863 . PMID   16845013. Archived from the original on 2010-04-09.

Further reading

This article incorporates text from the public domain Pfam and InterPro: IPR008426