CENPA

Centromere protein A, also known as CENPA, is a protein which in humans is encoded by the CENPA gene.[5]

CENPA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3AN2, 3NQJ, 3NQU, 3R45, 3WTP, 5CVD
Identifiers
Aliases	CENPA, CENP-A, CenH3, centromere protein A
External IDs	OMIM: 117139 MGI: 88375 HomoloGene: 1369 GeneCards: CENPA
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p23.3 Start 26,764,289 bp[1] End 26,801,067 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5 B1|5 16.76 cM Start 30,666,777 bp[2] End 30,674,830 bp[2]
Gene ontology Molecular function • DNA binding • chromatin binding • GO:0001948 protein binding • protein heterodimerization activity • nucleosomal DNA binding Cellular component • condensed chromosome inner kinetochore • condensed chromosome kinetochore • cytosol • nucleoplasm • chromosome • condensed nuclear chromosome kinetochore • chromosome, centromeric region • cell nucleus • kinetochore • condensed nuclear chromosome, centromeric region • nuclear nucleosome • nuclear pericentric heterochromatin • nucleosome Biological process • CENP-A containing nucleosome assembly • establishment of mitotic spindle orientation • protein localization to chromosome, centromeric region • GO:0022415 viral process • kinetochore assembly • sister chromatid cohesion • mitotic cytokinesis • cell cycle • cell division • nucleosome assembly Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1058	12615
Ensembl	ENSG00000115163	ENSMUSG00000029177
UniProt	P49450	O35216
RefSeq (mRNA)	NM_001809 NM_001042426	NM_007681 NM_001302129 NM_001302130 NM_001302131 NM_001302132
RefSeq (protein)	NP_001035891 NP_001800	NP_001289058 NP_001289059 NP_001289060 NP_001289061 NP_031707
Location (UCSC)	Chr 2: 26.76 – 26.8 Mb	Chr 5: 30.67 – 30.67 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Centromeres are the chromosomal domains that specify the mitotic behavior of chromosomes. The CENPA gene encodes a centromere protein which contains a histone H3 related histone fold domain that is required for targeting to the centromere. CENPA is proposed to be a component of a modified nucleosome or nucleosome-like structure in which it replaces 1 or both copies of conventional histone H3 in the (H3-H4)2 tetrameric core of the nucleosome particle. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[5]

In higher eukaryotes, the recruitment of CENP-A nucleosomes to existing centromeres is an epigenetic process, independent of the underlying DNA sequence. In S. pombe, de novo recruitment of the CENP-A to the centromere is believed to be controlled by "centromeric" heterochromatin surrounding the centromere, and by an RNAi mechanism. The RNAi is cut to form siRNA; this complexes with the protein Chp1, which then binds the centromeric heterochromatin. This helps recruit other proteins, ultimately resulting in a protein complex that forms cohesin between two sister chromatids at the centromeric heterochromatin. This cohesin is believed to be essential in replacing the centromere H3 with CENP-A. CENP-A is one of the epigenetic changes that is believed to distinguish centromeric DNA from other DNA.[6] Once the CENP-A has been added, the centromere becomes self-propagating, and the surrounding heterochromatin/RNAi mechanism is no longer necessary.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000115163 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029177 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. EntrezGene 1058
6. Chueh AC, Wong LH, Wong N, Choo KH (January 2005). "Variable and hierarchical size distribution of L1-retroelement-enriched CENP-A clusters within a functional human neocentromere". Hum. Mol. Genet. 14 (1): 85–93. doi:10.1093/hmg/ddi008. PMID 15537667.
7. Folco HD, Pidoux AL, Urano T, Allshire RC (January 2008). "Heterochromatin and RNAi are required to establish CENP-A chromatin at centromeres". Science. 319 (5859): 94–7. doi:10.1126/science.1150944. PMC 2586718. PMID 18174443.

External links

• Human CENPA genome location and CENPA gene details page in the UCSC Genome Browser.

Further reading

• Palmer DK, O'Day K, Trong HL, Charbonneau H, Margolis RL (1991). "Purification of the centromere-specific protein CENP-A and demonstration that it is a distinctive histone". Proc. Natl. Acad. Sci. U.S.A. 88 (9): 3734–8. doi:10.1073/pnas.88.9.3734. PMC 51527. PMID 2023923.
• Sullivan KF, Hechenberger M, Masri K (1994). "Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere". J. Cell Biol. 127 (3): 581–92. doi:10.1083/jcb.127.3.581. PMC 2120219. PMID 7962047.
• Shelby RD, Vafa O, Sullivan KF (1997). "Assembly of CENP-A into centromeric chromatin requires a cooperative array of nucleosomal DNA contact sites". J. Cell Biol. 136 (3): 501–13. doi:10.1083/jcb.136.3.501. PMC 2134286. PMID 9024683.
• Valdivia MM, Figueroa J, Iglesias C, Ortíz M (1998). "A novel centromere monospecific serum to a human autoepitope on the histone H3-like protein CENP-A". FEBS Lett. 422 (1): 5–9. doi:10.1016/S0014-5793(97)01583-4. PMID 9475158.
• Fowler KJ, Newson AJ, MacDonald AC, Kalitsis P, Lyu MS, Kozak CA, Choo KH (1998). "Chromosomal localization of mouse Cenpa gene". Cytogenet. Cell Genet. 79 (3–4): 298–301. doi:10.1159/000134748. PMID 9605877.
• Muro Y, Azuma N, Onouchi H, Kunimatsu M, Tomita Y, Sasaki M, Sugimoto K (2000). "Autoepitopes on autoantigen centromere protein-A (CENP-A) are restricted to the N-terminal region, which has no homology with histone H3". Clin. Exp. Immunol. 120 (1): 218–23. doi:10.1046/j.1365-2249.2000.01189.x. PMC 1905620. PMID 10759786.
• Lomonte P, Sullivan KF, Everett RD (2001). "Degradation of nucleosome-associated centromeric histone H3-like protein CENP-A induced by herpes simplex virus type 1 protein ICP0". J. Biol. Chem. 276 (8): 5829–35. doi:10.1074/jbc.M008547200. PMID 11053442.
• Uren AG, Wong L, Pakusch M, Fowler KJ, Burrows FJ, Vaux DL, Choo KH (2001). "Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype". Curr. Biol. 10 (21): 1319–28. doi:10.1016/S0960-9822(00)00769-7. PMID 11084331.
• Zeitlin SG, Shelby RD, Sullivan KF (2002). "CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis". J. Cell Biol. 155 (7): 1147–57. doi:10.1083/jcb.200108125. PMC 2199334. PMID 11756469.
• Ando S, Yang H, Nozaki N, Okazaki T, Yoda K (2002). "CENP-A, -B, and -C chromatin complex that contains the I-type alpha-satellite array constitutes the prekinetochore in HeLa cells". Mol. Cell. Biol. 22 (7): 2229–41. doi:10.1128/MCB.22.7.2229-2241.2002. PMC 133672. PMID 11884609.
• Saxena A, Saffery R, Wong LH, Kalitsis P, Choo KH (2002). "Centromere proteins Cenpa, Cenpb, and Bub3 interact with poly(ADP-ribose) polymerase-1 protein and are poly(ADP-ribosyl)ated". J. Biol. Chem. 277 (30): 26921–6. doi:10.1074/jbc.M200620200. PMID 12011073.
• Figueroa J, Pendón C, Valdivia MM (2003). "Molecular cloning and sequence analysis of hamster CENP-A cDNA". BMC Genomics. 3: 11. doi:10.1186/1471-2164-3-11. PMC 113255. PMID 12019018.
• Saxena A, Wong LH, Kalitsis P, Earle E, Shaffer LG, Choo KH (2003). "Poly(ADP-ribose) polymerase 2 localizes to mammalian active centromeres and interacts with PARP-1, Cenpa, Cenpb and Bub3, but not Cenpc". Hum. Mol. Genet. 11 (19): 2319–29. doi:10.1093/hmg/11.19.2319. PMID 12217960.
• Tomonaga T, Matsushita K, Yamaguchi S, Oohashi T, Shimada H, Ochiai T, Yoda K, Nomura F (2003). "Overexpression and mistargeting of centromere protein-A in human primary colorectal cancer". Cancer Res. 63 (13): 3511–6. PMID 12839935.
• Kunitoku N, Sasayama T, Marumoto T, Zhang D, Honda S, Kobayashi O, Hatakeyama K, Ushio Y, Saya H, Hirota T (2004). "CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function". Dev. Cell. 5 (6): 853–64. doi:10.1016/S1534-5807(03)00364-2. PMID 14667408.
• Obuse C, Yang H, Nozaki N, Goto S, Okazaki T, Yoda K (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.
• Yasuda S, Oceguera-Yanez F, Kato T, Okamoto M, Yonemura S, Terada Y, Ishizaki T, Narumiya S (2004). "Cdc42 and mDia3 regulate microtubule attachment to kinetochores". Nature. 428 (6984): 767–71. doi:10.1038/nature02452. PMID 15085137.
• Black BE, Foltz DR, Chakravarthy S, Luger K, Woods VL Jr, Cleveland DW (2004). "Structural determinants for generating centromeric chromatin". Nature. 430 (6999): 578–82. doi:10.1038/nature02766. PMID 15282608.
• Sullivan BA, Karpen GH (2004). "Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin". Nat. Struct. Mol. Biol. 11 (11): 1076–83. doi:10.1038/nsmb845. PMC 1283111. PMID 15475964.
• Nikolina S, Basset EA, Robers DJ, Black BE (2010). "The structure of (CENP-A?H4)2 reveals physical features that mark centromeres". Nature. 467 (7313): 347–351. doi:10.1038/nature09323. PMC 2946842. PMID 20739937.