Biology:CENPH

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example
CENP-H
Identifiers
SymbolCENP-H
PfamPF05837
InterProIPR008426

Centromere protein H is a protein that in humans is encoded by the CENPH gene.[1][2][3] It is involved in the assembly of kinetochore proteins, mitotic progression and chromosome segregation.[4][5]

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.[6] 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.[7] CENP-H contains a coiled-coil structure and a nuclear localisation signal.[7]

Studies show that CENP-H may be associated with certain human cancers.[8][9]

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.[10]

Interactions

CENPH has also been shown to interact with KIAA0090.[11] The significance of this interaction is unclear.

References

  1. "Human CENP-H multimers colocalize with CENP-A and CENP-C at active centromere--kinetochore complexes". Human Molecular Genetics 9 (19): 2919–2926. November 2000. doi:10.1093/hmg/9.19.2919. PMID 11092768. 
  2. "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1". Nature Cell Biology 6 (11): 1135–1141. November 2004. doi:10.1038/ncb1187. PMID 15502821. 
  3. "Entrez Gene: CENPH centromere protein H". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=64946. 
  4. "The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity". The EMBO Journal 26 (24): 5033–5047. December 2007. doi:10.1038/sj.emboj.7601927. PMID 18007590. 
  5. "RNAi knockdown of human kinetochore protein CENP-H". Biochemical and Biophysical Research Communications 348 (1): 36–46. September 2006. doi:10.1016/j.bbrc.2006.06.187. PMID 16875666. 
  6. "CENP-H, a constitutive centromere component, is required for centromere targeting of CENP-C in vertebrate cells". The EMBO Journal 20 (16): 4603–4617. August 2001. doi:10.1093/emboj/20.16.4603. PMID 11500386. 
  7. 7.0 7.1 "Characterization of a novel kinetochore protein, CENP-H". The Journal of Biological Chemistry 274 (39): 27343–27346. September 1999. doi:10.1074/jbc.274.39.27343. PMID 10488063. 
  8. "Prognostic relevance of Centromere protein H expression in esophageal carcinoma". BMC Cancer 8: 233. August 2008. doi:10.1186/1471-2407-8-233. PMID 18700042. 
  9. "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. January 2007. doi:10.1158/1078-0432.CCR-06-1512. PMID 17255272. 
  10. "Molecular analysis of kinetochore architecture in fission yeast". The EMBO Journal 24 (16): 2919–2930. August 2005. doi:10.1038/sj.emboj.7600762. PMID 16079914. 
  11. "APID: Agile Protein Interaction DataAnalyzer". Nucleic Acids Research 34 (Web Server issue): W298–W302. July 2006. doi:10.1093/nar/gkl128. PMID 16845013. PMC 1538863. http://bioinfow.dep.usal.es/apid/html/home.htm. 

External links

Further reading

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