Centromere protein H is a protein that in humans is encoded by the CENPHgene.[5][6][7] It is involved in the assembly of kinetochore proteins, mitotic progression and chromosome segregation.[8][9]
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-coilstructure and a nuclear localisation signal.[11]
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.
^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. PMID15502821. S2CID39408000.
^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. PMID16875666.
^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. PMID17255272. S2CID474452.
Tomonaga T, Matsushita K, Ishibashi M, Nezu M, Shimada H, Ochiai T, et al. (June 2005). "Centromere protein H is up-regulated in primary human colorectal cancer and its overexpression induces aneuploidy". Cancer Research. 65 (11): 4683–4689. doi:10.1158/0008-5472.CAN-04-3613. PMID15930286.
Foltz DR, Jansen LE, Black BE, Bailey AO, Yates JR, Cleveland DW (May 2006). "The human CENP-A centromeric nucleosome-associated complex". Nature Cell Biology. 8 (5): 458–469. doi:10.1038/ncb1397. PMID16622419. S2CID205286556.
Okada M, Cheeseman IM, Hori T, Okawa K, McLeod IX, Yates JR, et al. (May 2006). "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. doi:10.1038/ncb1396. PMID16622420. S2CID26974412.
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. PMID16875666.
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. PMID17255272. S2CID474452.
