CENP-A

CENPA
PDBに登録されている構造
PDB	オルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧
	3AN2, 3NQJ, 3NQU, 3R45, 3WTP, 5CVD
識別子
記号	CENPA, CENP-A, CenH3, centromere protein A
外部ID	OMIM: 117139 MGI: 88375 HomoloGene: 1369 GeneCards: CENPA
遺伝子の位置 (ヒト)
染色体	2番染色体 (ヒト)
終点	26,801,067 bp
遺伝子の位置 (マウス)
染色体	5番染色体 (マウス)
終点	30,832,174 bp
遺伝子オントロジー
分子機能	• DNA結合; • クロマチン結合; • 血漿タンパク結合; • protein heterodimerization activity; • nucleosomal DNA binding;
細胞の構成要素	• inner kinetochore; • 細胞質基質; • 核質; • 染色体; • セントロメア; • 細胞核; • 動原体; • ヌクレオソーム;
生物学的プロセス	• CENP-A containing chromatin assembly; • establishment of mitotic spindle orientation; • protein localization to chromosome, centromeric region; • viral process; • kinetochore assembly; • sister chromatid cohesion; • mitotic cytokinesis; • 細胞周期; • 細胞分裂; • nucleosome assembly;
	出典:Amigo / QuickGO
オルソログ
	1058
	12615
	ENSG00000115163
	ENSMUSG00000029177
	P49450
	O35216
	NM_001809; NM_001042426
	NM_007681; NM_001302129; NM_001302130; NM_001302131; NM_001302132
	NP_001035891; NP_001800
	NP_001289058; NP_001289059; NP_001289060; NP_001289061; NP_031707
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

CENP-A（centromere protein A）は、ヒトではCENPA遺伝子にコードされるタンパク質である^[5]。CENP-AはヒストンH3のバリアントであり、ヒトを含む大部分の真核生物において各染色体上のキネトコアの位置の決定に重要な因子である^[6]。

概要 CENPA, PDBに登録されている構造 ...

閉じる

CENP-Aは、各染色体上のセントロメアの位置をエピジェネティックに定義するタンパク質であり^[7]、有糸分裂時のキネトコアの組み立ての位置と姉妹染色分体間の最終的な接着部位を決定する。CENP-Aタンパク質はヒストンH3のバリアントであり、セントロメアクロマチン内の一部のヌクレオソームで典型的ヒストンH3に置き換わって存在している^[8]^[9]。このタンパク質はセントロメアに恒常的に存在しており、セントロメアヘテロクロマチンと関係した典型的ヒストンの変化が付随していることが多い^[10]。CENP-AはヒストンH3のバリアント中で最も配列多様性が高く、典型的ヒストンH3と比較して48%の配列類似性がみられるのみである。また、そのN末端テールも高度に多様化しており、H3K4、H3K9、H3K27など詳細な特性解析がなされているヒストン修飾部位の多くを欠いている^[11]。

ヒストンとしては異例なことであるが、CENP-A含有ヌクレオソームはDNA複製とともにロードされるわけではなく、ヒトではG₁期^[12]、ショウジョウバエではM期^[13]、分裂酵母ではG₂期^[14]など、生物種によってさまざまな細胞周期段階でクロマチンへロードされる。この特殊なローディングを行うためにCENP-A特異的なヒストンシャペロンが存在し、ヒトではHJURP（英語版）、ショウジョウバエではCAL1、分裂酵母ではScm3がその役割を担っている^[15]。大部分の真核生物では、CENP-Aは高度反復サテライトDNAの大きなドメインへロードされる^[16]。サテライトDNA内のCENP-Aの位置はタンパク質レベルで、完全にエピジェネティックな機構で遺伝する^[17]。すなわち、ゲノム内でのCENP-Aの結合位置はDNA配列とは無関係に細胞分裂時に娘細胞へコピーされる。CENP-Aが染色体から失われた場合に備えてヒト細胞にはフェイルセーフ機構が存在することが記載されており、CENP-B（英語版）がサテライトDNA結合ドメインを介してCENP-Aをリクルートし、セントロメア内にCENP-A含有ヌクレオソームを再導入する^[18]。

CENP-Aはキネトコアのinner kinetochoreと呼ばれる領域でCENP-C（英語版）、CENP-N（英語版）などのタンパク質と直接相互作用する^[19]^[20]。こうした相互作用を介して、有糸分裂時に微小管は染色体を正確に分離することができるようになる。

[1]
GRCh38: Ensembl release 89: ENSG00000115163 - Ensembl, May 2017
[2]
GRCm38: Ensembl release 89: ENSMUSG00000029177 - Ensembl, May 2017
[3]
Human PubMed Reference:
[4]
Mouse PubMed Reference:
[5]
“CENPA centromere protein A [Homo sapiens (human) - Gene - NCBI]”. www.ncbi.nlm.nih.gov. 2023年6月3日閲覧。
[6]
“Epigenetic regulation of centromeric chromatin: old dogs, new tricks?”. Nature Reviews. Genetics 9 (12): 923–937. (December 2008). doi:10.1038/nrg2466. PMC 2586333. PMID 19002142.
[7]
“A two-step mechanism for epigenetic specification of centromere identity and function”. Nature Cell Biology 15 (9): 1056–1066. (September 2013). doi:10.1038/ncb2805. PMC 4418506. PMID 23873148.
[8]
“Conserved organization of centromeric chromatin in flies and humans”. Developmental Cell 2 (3): 319–330. (March 2002). doi:10.1016/s1534-5807(02)00135-1. PMC 3192492. PMID 11879637.
[9]
“Human centromeric CENP-A chromatin is a homotypic, octameric nucleosome at all cell cycle points”. The Journal of Cell Biology 216 (3): 607–621. (March 2017). doi:10.1083/jcb.201608083. PMC 5350519. PMID 28235947.
[10]
“Complete genomic and epigenetic maps of human centromeres”. Science 376 (6588): eabl4178. (April 2022). doi:10.1126/science.abl4178. PMC 9233505. PMID 35357911.
[11]
“Posttranslational modifications of CENP-A: marks of distinction”. Chromosoma 127 (3): 279–290. (September 2018). doi:10.1007/s00412-018-0665-x. PMC 6082721. PMID 29569072.
[12]
“Propagation of centromeric chromatin requires exit from mitosis”. The Journal of Cell Biology 176 (6): 795–805. (March 2007). doi:10.1083/jcb.200701066. PMC 2064054. PMID 17339380.
[13]
“Incorporation of Drosophila CID/CENP-A and CENP-C into centromeres during early embryonic anaphase”. Current Biology 17 (3): 237–243. (February 2007). doi:10.1016/j.cub.2006.11.051. hdl:11858/00-001M-0000-002A-23E4-7. PMID 17222555.
[14]
“Centromere DNA Destabilizes H3 Nucleosomes to Promote CENP-A Deposition during the Cell Cycle”. Current Biology 28 (24): 3924–3936.e4. (December 2018). doi:10.1016/j.cub.2018.10.049. PMC 6303189. PMID 30503616.
[15]
“Histone chaperones: assisting histone traffic and nucleosome dynamics”. Annual Review of Biochemistry 83: 487–517. (2014). doi:10.1146/annurev-biochem-060713-035536. PMID 24905786.
[16]
“Centromere identity from the DNA point of view”. Chromosoma 123 (4): 313–325. (August 2014). doi:10.1007/s00412-014-0462-0. PMC 4107277. PMID 24763964.
[17]
“Genomic variation within alpha satellite DNA influences centromere location on human chromosomes with metastable epialleles”. Genome Research 26 (10): 1301–1311. (October 2016). doi:10.1101/gr.206706.116. PMC 5052062. PMID 27510565.
[18]
“Centromeres: genetic input to calibrate an epigenetic feedback loop”. The EMBO Journal 39 (20): e106638. (October 2020). doi:10.15252/embj.2020106638. PMC 7560195. PMID 32959893.
[19]
“The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle”. Open Biology 10 (6): 200051. (June 2020). doi:10.1098/rsob.200051. PMC 7333888. PMID 32516549.
[20]
“Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome”. Nature 574 (7777): 278–282. (October 2019). Bibcode: 2019Natur.574..278Y. doi:10.1038/s41586-019-1609-1. PMC 6859074. PMID 31578520.

“Purification of the centromere-specific protein CENP-A and demonstration that it is a distinctive histone”. Proceedings of the National Academy of Sciences of the United States of America 88 (9): 3734–3738. (May 1991). Bibcode: 1991PNAS...88.3734P. doi:10.1073/pnas.88.9.3734. PMC 51527. PMID 2023923.
“Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere”. The Journal of Cell Biology 127 (3): 581–592. (November 1994). doi:10.1083/jcb.127.3.581. PMC 2120219. PMID 7962047.
“Assembly of CENP-A into centromeric chromatin requires a cooperative array of nucleosomal DNA contact sites”. The Journal of Cell Biology 136 (3): 501–513. (February 1997). doi:10.1083/jcb.136.3.501. PMC 2134286. PMID 9024683.
“A novel centromere monospecific serum to a human autoepitope on the histone H3-like protein CENP-A”. FEBS Letters 422 (1): 5–9. (January 1998). doi:10.1016/S0014-5793(97)01583-4. PMID 9475158.
“Chromosomal localization of mouse Cenpa gene”. Cytogenetics and Cell Genetics 79 (3–4): 298–301. (1998). doi:10.1159/000134748. PMID 9605877.
“Autoepitopes on autoantigen centromere protein-A (CENP-A) are restricted to the N-terminal region, which has no homology with histone H3”. Clinical and Experimental Immunology 120 (1): 218–223. (April 2000). doi:10.1046/j.1365-2249.2000.01189.x. PMC 1905620. PMID 10759786.
“Degradation of nucleosome-associated centromeric histone H3-like protein CENP-A induced by herpes simplex virus type 1 protein ICP0”. The Journal of Biological Chemistry 276 (8): 5829–5835. (February 2001). doi:10.1074/jbc.M008547200. PMID 11053442.
“Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype”. Current Biology 10 (21): 1319–1328. (November 2000). doi:10.1016/S0960-9822(00)00769-7. PMID 11084331.
“CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis”. The Journal of Cell Biology 155 (7): 1147–1157. (December 2001). doi:10.1083/jcb.200108125. PMC 2199334. PMID 11756469.
“CENP-A, -B, and -C chromatin complex that contains the I-type alpha-satellite array constitutes the prekinetochore in HeLa cells”. Molecular and Cellular Biology 22 (7): 2229–2241. (April 2002). doi:10.1128/MCB.22.7.2229-2241.2002. PMC 133672. PMID 11884609.
“Centromere proteins Cenpa, Cenpb, and Bub3 interact with poly(ADP-ribose) polymerase-1 protein and are poly(ADP-ribosyl)ated”. The Journal of Biological Chemistry 277 (30): 26921–26926. (July 2002). doi:10.1074/jbc.M200620200. PMID 12011073.
“Molecular cloning and sequence analysis of hamster CENP-A cDNA”. BMC Genomics 3: 11. (May 2002). doi:10.1186/1471-2164-3-11. PMC 113255. PMID 12019018.
“Poly(ADP-ribose) polymerase 2 localizes to mammalian active centromeres and interacts with PARP-1, Cenpa, Cenpb and Bub3, but not Cenpc”. Human Molecular Genetics 11 (19): 2319–2329. (September 2002). doi:10.1093/hmg/11.19.2319. PMID 12217960.
“Overexpression and mistargeting of centromere protein-A in human primary colorectal cancer”. Cancer Research 63 (13): 3511–3516. (July 2003). PMID 12839935.
“CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function”. Developmental Cell 5 (6): 853–864. (December 2003). doi:10.1016/S1534-5807(03)00364-2. PMID 14667408.
“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). doi:10.1111/j.1365-2443.2004.00705.x. PMID 15009096.
“Cdc42 and mDia3 regulate microtubule attachment to kinetochores”. Nature 428 (6984): 767–771. (April 2004). Bibcode: 2004Natur.428..767Y. doi:10.1038/nature02452. PMID 15085137.
“Structural determinants for generating centromeric chromatin”. Nature 430 (6999): 578–582. (July 2004). Bibcode: 2004Natur.430..578B. doi:10.1038/nature02766. PMID 15282608.
“Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin”. Nature Structural & Molecular Biology 11 (11): 1076–1083. (November 2004). doi:10.1038/nsmb845. PMC 1283111. PMID 15475964.
“The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres”. Nature 467 (7313): 347–351. (September 2010). Bibcode: 2010Natur.467..347S. doi:10.1038/nature09323. PMC 2946842. PMID 20739937.

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

[refGRCh38Ensembl-1] [1]
GRCh38: Ensembl release 89: ENSG00000115163 - Ensembl, May 2017

[refGRCm38Ensembl-2] [2]
GRCm38: Ensembl release 89: ENSMUSG00000029177 - Ensembl, May 2017

[3] [3]
Human PubMed Reference:

[4] [4]
Mouse PubMed Reference:

[5] [5]
“CENPA centromere protein A [Homo sapiens (human) - Gene - NCBI]”. www.ncbi.nlm.nih.gov. 2023年6月3日閲覧。

[:0-6] [6]
“Epigenetic regulation of centromeric chromatin: old dogs, new tricks?”. Nature Reviews. Genetics 9 (12): 923–937. (December 2008). doi:10.1038/nrg2466. PMC 2586333. PMID 19002142.

[:1-7] [7]
“A two-step mechanism for epigenetic specification of centromere identity and function”. Nature Cell Biology 15 (9): 1056–1066. (September 2013). doi:10.1038/ncb2805. PMC 4418506. PMID 23873148.

[:3-8] [8]
“Conserved organization of centromeric chromatin in flies and humans”. Developmental Cell 2 (3): 319–330. (March 2002). doi:10.1016/s1534-5807(02)00135-1. PMC 3192492. PMID 11879637.

[:4-9] [9]
“Human centromeric CENP-A chromatin is a homotypic, octameric nucleosome at all cell cycle points”. The Journal of Cell Biology 216 (3): 607–621. (March 2017). doi:10.1083/jcb.201608083. PMC 5350519. PMID 28235947.

[:2-10] [10]
“Complete genomic and epigenetic maps of human centromeres”. Science 376 (6588): eabl4178. (April 2022). doi:10.1126/science.abl4178. PMC 9233505. PMID 35357911.

[:5-11] [11]
“Posttranslational modifications of CENP-A: marks of distinction”. Chromosoma 127 (3): 279–290. (September 2018). doi:10.1007/s00412-018-0665-x. PMC 6082721. PMID 29569072.

[:6-12] [12]
“Propagation of centromeric chromatin requires exit from mitosis”. The Journal of Cell Biology 176 (6): 795–805. (March 2007). doi:10.1083/jcb.200701066. PMC 2064054. PMID 17339380.

[:7-13] [13]
“Incorporation of Drosophila CID/CENP-A and CENP-C into centromeres during early embryonic anaphase”. Current Biology 17 (3): 237–243. (February 2007). doi:10.1016/j.cub.2006.11.051. hdl:11858/00-001M-0000-002A-23E4-7. PMID 17222555.

[:8-14] [14]
“Centromere DNA Destabilizes H3 Nucleosomes to Promote CENP-A Deposition during the Cell Cycle”. Current Biology 28 (24): 3924–3936.e4. (December 2018). doi:10.1016/j.cub.2018.10.049. PMC 6303189. PMID 30503616.

[:9-15] [15]
“Histone chaperones: assisting histone traffic and nucleosome dynamics”. Annual Review of Biochemistry 83: 487–517. (2014). doi:10.1146/annurev-biochem-060713-035536. PMID 24905786.

[:10-16] [16]
“Centromere identity from the DNA point of view”. Chromosoma 123 (4): 313–325. (August 2014). doi:10.1007/s00412-014-0462-0. PMC 4107277. PMID 24763964.

[:11-17] [17]
“Genomic variation within alpha satellite DNA influences centromere location on human chromosomes with metastable epialleles”. Genome Research 26 (10): 1301–1311. (October 2016). doi:10.1101/gr.206706.116. PMC 5052062. PMID 27510565.

[:12-18] [18]
“Centromeres: genetic input to calibrate an epigenetic feedback loop”. The EMBO Journal 39 (20): e106638. (October 2020). doi:10.15252/embj.2020106638. PMC 7560195. PMID 32959893.

[:13-19] [19]
“The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle”. Open Biology 10 (6): 200051. (June 2020). doi:10.1098/rsob.200051. PMC 7333888. PMID 32516549.

[:14-20] [20]
“Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome”. Nature 574 (7777): 278–282. (October 2019). Bibcode: 2019Natur.574..278Y. doi:10.1038/s41586-019-1609-1. PMC 6859074. PMID 31578520.

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[6]

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[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

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CENP-A

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