CENPH explained

Symbol:	CENP-H
CENP-H
Pfam:	PF05837
Interpro:	IPR008426

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.

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.

Further reading

• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA . 6 . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proceedings of the National Academy of Sciences of the United States of America . 99 . 26 . 16899–16903 . December 2002 . 12477932 . 139241 . 10.1073/pnas.242603899 . free . 2002PNAS...9916899M .
• Saffery R, Sumer H, Hassan S, Wong LH, Craig JM, Todokoro K, Anderson M, Stafford A, Choo KH . 6 . Transcription within a functional human centromere . Molecular Cell . 12 . 2 . 509–516 . August 2003 . 14536089 . 10.1016/S1097-2765(03)00279-X . free . 10536/DRO/DU:30119197 . free .
• Obuse C, Yang H, Nozaki N, Goto S, Okazaki T, Yoda K . 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 to Cells . 9 . 2 . 105–120 . February 2004 . 15009096 . 10.1111/j.1365-2443.2004.00705.x . 21813024 . free .
• Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J . 6 . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Research . 14 . 10B . 2121–2127 . October 2004 . 15489334 . 528928 . 10.1101/gr.2596504 .
• Mikami Y, Hori T, Kimura H, Fukagawa T . The functional region of CENP-H interacts with the Nuf2 complex that localizes to centromere during mitosis . Molecular and Cellular Biology . 25 . 5 . 1958–1970 . March 2005 . 15713649 . 549355 . 10.1128/MCB.25.5.1958-1970.2005 .
• Tomonaga T, Matsushita K, Ishibashi M, Nezu M, Shimada H, Ochiai T, Yoda K, Nomura F . 6 . Centromere protein H is up-regulated in primary human colorectal cancer and its overexpression induces aneuploidy . Cancer Research . 65 . 11 . 4683–4689 . June 2005 . 15930286 . 10.1158/0008-5472.CAN-04-3613 .
• Foltz DR, Jansen LE, Black BE, Bailey AO, Yates JR, Cleveland DW . The human CENP-A centromeric nucleosome-associated complex . Nature Cell Biology . 8 . 5 . 458–469 . May 2006 . 16622419 . 10.1038/ncb1397 . 205286556 .
• Okada M, Cheeseman IM, Hori T, Okawa K, McLeod IX, Yates JR, Desai A, Fukagawa T . 6 . The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres . Nature Cell Biology . 8 . 5 . 446–457 . May 2006 . 16622420 . 10.1038/ncb1396 . 26974412 .
• Izuta H, Ikeno M, Suzuki N, Tomonaga T, Nozaki N, Obuse C, Kisu Y, Goshima N, Nomura F, Nomura N, Yoda K . 6 . Comprehensive analysis of the ICEN (Interphase Centromere Complex) components enriched in the CENP-A chromatin of human cells . Genes to Cells . 11 . 6 . 673–684 . June 2006 . 16716197 . 10.1111/j.1365-2443.2006.00969.x . 45931410 . free .
• Orthaus S, Ohndorf S, Diekmann S . RNAi knockdown of human kinetochore protein CENP-H . Biochemical and Biophysical Research Communications . 348 . 1 . 36–46 . September 2006 . 16875666 . 10.1016/j.bbrc.2006.06.187 .
• 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 . 6 . 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 . 17255272 . 10.1158/1078-0432.CCR-06-1512 . 474452 .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . 6 . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .

Notes and References

1. Sugata N, Li S, Earnshaw WC, Yen TJ, Yoda K, Masumoto H, Munekata E, Warburton PE, Todokoro K . 6 . 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 . 11092768 . 10.1093/hmg/9.19.2919 . free .
2. Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M . 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 . 15502821 . 10.1038/ncb1187 . 39408000 .
3. Web site: Entrez Gene: CENPH centromere protein H.
4. McClelland SE, Borusu S, Amaro AC, Winter JR, Belwal M, McAinsh AD, Meraldi P . The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity . The EMBO Journal . 26 . 24 . 5033–5047 . December 2007 . 18007590 . 2140114 . 10.1038/sj.emboj.7601927 .
5. Orthaus S, Ohndorf S, Diekmann S . RNAi knockdown of human kinetochore protein CENP-H . Biochemical and Biophysical Research Communications . 348 . 1 . 36–46 . September 2006 . 16875666 . 10.1016/j.bbrc.2006.06.187 .
6. Fukagawa T, Mikami Y, Nishihashi A, Regnier V, Haraguchi T, Hiraoka Y, Sugata N, Todokoro K, Brown W, Ikemura T . 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 . 11500386 . 125570 . 10.1093/emboj/20.16.4603 .
7. Sugata N, Munekata E, Todokoro K . Characterization of a novel kinetochore protein, CENP-H . The Journal of Biological Chemistry . 274 . 39 . 27343–27346 . September 1999 . 10488063 . 10.1074/jbc.274.39.27343 . free .
8. Guo XZ, Zhang G, Wang JY, Liu WL, Wang F, Dong JQ, Xu LH, Cao JY, Song LB, Zeng MS . 6 . Prognostic relevance of Centromere protein H expression in esophageal carcinoma . BMC Cancer . 8 . 233 . August 2008 . 18700042 . 2535782 . 10.1186/1471-2407-8-233 . free .
9. 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 . 6 . 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 . 17255272 . 10.1158/1078-0432.CCR-06-1512 . 474452 .
10. Liu X, McLeod I, Anderson S, Yates JR, He X . Molecular analysis of kinetochore architecture in fission yeast . The EMBO Journal . 24 . 16 . 2919–2930 . August 2005 . 16079914 . 1187945 . 10.1038/sj.emboj.7600762 .
11. Prieto C, De Las Rivas J . APID: Agile Protein Interaction DataAnalyzer . Nucleic Acids Research . 34 . Web Server issue . W298–W302 . July 2006 . 16845013 . 1538863 . 10.1093/nar/gkl128 . dead . https://web.archive.org/web/20100409025355/http://bioinfow.dep.usal.es/apid/html/home.htm . 2010-04-09 .