CENPH

Centromere protein H
Identifiers
Symbols	CENPH ; NNF1; PMF1
External IDs	OMIM: 605607 MGI: 1349448 HomoloGene: 32519 GeneCards: CENPH Gene
Gene ontology Molecular function • protein binding • kinetochore binding Cellular component • kinetochore • condensed chromosome kinetochore • nucleus • nucleoplasm • cytosol Biological process • mitotic cell cycle • nucleosome assembly • small GTPase mediated signal transduction • CENP-A containing nucleosome assembly • kinetochore assembly • kinetochore organization Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	64946	26886
Ensembl	ENSG00000153044	ENSMUSG00000045273
UniProt	Q9H3R5	Q9QYM8
RefSeq (mRNA)	NM_022909	NM_021886
RefSeq (protein)	NP_075060	NP_068686
Location (UCSC)	Chr 5: 69.19 – 69.21 Mb	Chr 13: 100.76 – 100.78 Mb
PubMed search

CENP-H
Identifiers
Symbol	CENP-H
Pfam	PF05837
InterPro	IPR008426
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Centromere protein H is a protein that in humans is encoded by the CENPH gene.^[1][2][3]

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.^[4] 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.^[5] CENP-H contains a coiled-coil structure and a nuclear localisation signal.^[5]

Studies show that CENP-H may be associated with certain human cancers.^[6][7]

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.^[8]

Other Protein Interactions

CENPH has also been shown to interact with KIAA0090.^[9] The significance of this interaction is unclear.

References

1. Sugata N, Li S, Earnshaw WC, Yen TJ, Yoda K, Masumoto H, Munekata E, Warburton PE, Todokoro K (Jan 2001). "Human CENP-H multimers colocalize with CENP-A and CENP-C at active centromere--kinetochore complexes". Hum Mol Genet 9 (19): 2919–26. doi:10.1093/hmg/9.19.2919. PMID 11092768.
2. Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M (Nov 2004). "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1". Nat Cell Biol 6 (11): 1135–41. doi:10.1038/ncb1187. PMID 15502821.
3. "Entrez Gene: CENPH centromere protein H".
4. Fukagawa, T.; Mikami, Y.; Nishihashi, A.; Regnier, V.; Haraguchi, T.; Hiraoka, Y.; Sugata, N.; Todokoro, K.; Brown, W.; Ikemura, T. (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.
5. Sugata N, Munekata E, Todokoro K (September 1999). "Characterization of a novel kinetochore protein, CENP-H". J. Biol. Chem. 274 (39): 27343–6. doi:10.1074/jbc.274.39.27343. PMID 10488063.
6. Guo XZ, Zhang G, Wang JY, Liu WL, Wang F, Dong JQ, Xu LH, Cao JY, Song LB, Zeng MS (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.
7. Liao WT, Song LB, Zhang HZ, Zhang X, Zhang L, Liu WL, Feng Y, Guo BH, Mai HQ, Cao SM, Li MZ, Qin HD, Zeng YX, Zeng MS (January 2007). "Centromere protein H is a novel prognostic marker for nasopharyngeal carcinoma progression and overall patient survival". Clin. Cancer Res. 13 (2 Pt 1): 508–14. doi:10.1158/1078-0432.CCR-06-1512. PMID 17255272.
8. Liu X, McLeod I, Anderson S, Yates JR, He X (August 2005). "Molecular analysis of kinetochore architecture in fission yeast". EMBO J. 24 (16): 2919–30. doi:10.1038/sj.emboj.7600762. PMC 1187945. PMID 16079914.
9. Prieto C, De Las Rivas J (July 2006). "APID: Agile Protein Interaction DataAnalyzer". Nucleic Acids Res. 34 (Web Server issue): W298–302. doi:10.1093/nar/gkl128. PMC 1538863. PMID 16845013.

Further reading

• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Saffery R, Sumer H, Hassan S; et al. (2003). "Transcription within a functional human centromere.". Mol. Cell 12 (2): 509–16. doi:10.1016/S1097-2765(03)00279-X. PMID 14536089.
• Obuse C, Yang H, Nozaki N; et al. (2004). "Proteomics analysis of the centromere complex from HeLa interphase cells: UV-damaged DNA binding protein 1 (DDB-1) is a component of the CEN-complex, while BMI-1 is transiently co-localized with the centromeric region in interphase.". Genes Cells 9 (2): 105–20. doi:10.1111/j.1365-2443.2004.00705.x. PMID 15009096.
• Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Mikami Y, Hori T, Kimura H, Fukagawa T (2005). "The functional region of CENP-H interacts with the Nuf2 complex that localizes to centromere during mitosis.". Mol. Cell. Biol. 25 (5): 1958–70. doi:10.1128/MCB.25.5.1958-1970.2005. PMC 549355. PMID 15713649.
• Tomonaga T, Matsushita K, Ishibashi M; et al. (2005). "Centromere protein H is up-regulated in primary human colorectal cancer and its overexpression induces aneuploidy.". Cancer Res. 65 (11): 4683–9. doi:10.1158/0008-5472.CAN-04-3613. PMID 15930286.
• Foltz DR, Jansen LE, Black BE; et al. (2006). "The human CENP-A centromeric nucleosome-associated complex.". Nat. Cell Biol. 8 (5): 458–69. doi:10.1038/ncb1397. PMID 16622419.
• Okada M, Cheeseman IM, Hori T; et al. (2006). "The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres.". Nat. Cell Biol. 8 (5): 446–57. doi:10.1038/ncb1396. PMID 16622420.
• Izuta H, Ikeno M, Suzuki N; et al. (2006). "Comprehensive analysis of the ICEN (Interphase Centromere Complex) components enriched in the CENP-A chromatin of human cells.". Genes Cells 11 (6): 673–84. doi:10.1111/j.1365-2443.2006.00969.x. PMID 16716197.
• Orthaus S, Ohndorf S, Diekmann S (2006). "RNAi knockdown of human kinetochore protein CENP-H.". Biochem. Biophys. Res. Commun. 348 (1): 36–46. doi:10.1016/j.bbrc.2006.06.187. PMID 16875666.
• Liao WT, Song LB, Zhang HZ; et al. (2007). "Centromere protein H is a novel prognostic marker for nasopharyngeal carcinoma progression and overall patient survival.". Clin. Cancer Res. 13 (2 Pt 1): 508–14. doi:10.1158/1078-0432.CCR-06-1512. PMID 17255272.
• 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.

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