CENPH

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. 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. CENP-H contains a coiled-coil structure and a nuclear localisation signal.

Studies show that CENP-H may be associated with certain human cancers.

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.

Interactions

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

References

References

1. (November 2000). "Human CENP-H multimers colocalize with CENP-A and CENP-C at active centromere--kinetochore complexes". Human Molecular Genetics.
2. (November 2004). "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1". Nature Cell Biology.
3. "Entrez Gene: CENPH centromere protein H".
4. (December 2007). "The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity". The EMBO Journal.
5. (September 2006). "RNAi knockdown of human kinetochore protein CENP-H". Biochemical and Biophysical Research Communications.
6. (August 2001). "CENP-H, a constitutive centromere component, is required for centromere targeting of CENP-C in vertebrate cells". The EMBO Journal.
7. (September 1999). "Characterization of a novel kinetochore protein, CENP-H". The Journal of Biological Chemistry.
8. (August 2008). "Prognostic relevance of Centromere protein H expression in esophageal carcinoma". BMC Cancer.
9. (January 2007). "Centromere protein H is a novel prognostic marker for nasopharyngeal carcinoma progression and overall patient survival". Clinical Cancer Research.
10. (August 2005). "Molecular analysis of kinetochore architecture in fission yeast". The EMBO Journal.
11. (July 2006). "APID: Agile Protein Interaction DataAnalyzer". Nucleic Acids Research.