Histone H3-like centromeric protein A

NameHistone H3-like centromeric protein A
Synonyms
  • CENP-A
  • Centromere autoantigen A
  • Centromere protein A
Gene NameCENPA
OrganismHuman
Amino acid sequence
>lcl|BSEQ0008859|Histone H3-like centromeric protein A
MGPRRRSRKPEAPRRRSPSPTPTPGPSRRGPSLGASSHQHSRRRQGWLKEIRKLQKSTHL
LIRKLPFSRLAREICVKFTRGVDFNWQAQALLALQEAAEAFLVHLFEDAYLLTLHAGRVT
LFPKDVQLARRIRGLEEGLG
Number of residues140
Molecular Weight15990.395
Theoretical pINot Available
GO Classification
Functions
  • DNA binding
  • chromatin binding
Processes
  • mitotic cell cycle
  • viral process
  • kinetochore assembly
  • nucleosome assembly
  • CENP-A containing nucleosome assembly
  • establishment of mitotic spindle orientation
  • protein localization to chromosome, centromeric region
  • small GTPase mediated signal transduction
Components
  • chromosome, centromeric region
  • condensed nuclear chromosome, centromeric region
  • nucleosome
  • condensed chromosome inner kinetochore
  • condensed nuclear chromosome kinetochore
  • nucleus
  • cytosol
  • nucleoplasm
General FunctionDna binding
Specific FunctionHistone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. The CENPA-H4 heterotetramer can bind DNA by itself (in vitro).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP49450
UniProtKB Entry NameCENPA_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0013459|Histone H3-like centromeric protein A (CENPA)
ATGGGCCCGCGCCGCCGGAGCCGAAAGCCCGAGGCCCCGAGGAGGCGCAGCCCGAGCCCG
ACCCCGACCCCCGGCCCCTCCCGGCGGGGCCCCTCCTTAGGCGCTTCCTCCCATCAACAC
AGTCGGCGGAGACAAGGTTGGCTAAAGGAGATCCGAAAGCTTCAGAAGAGCACACACCTC
TTGATAAGGAAGCTGCCCTTCAGCCGCCTGGCAGCAGAAGCATTTCTAGTTCATCTCTTT
GAGGACGCCTATCTCCTCACCTTACATGCAGGCCGAGTTACTCTCTTCCCAAAGGATGTG
CAACTGGCCCGGAGGATCCGGGGCCTTGAGGAGGGACTCGGCTGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:1851
Chromosome Location2
LocusNot Available
References
  1. Sullivan KF, Hechenberger M, Masri K: Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere. J Cell Biol. 1994 Nov;127(3):581-92. 7962047
  2. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. 15815621
  3. 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: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  4. Shelby RD, Vafa O, Sullivan KF: Assembly of CENP-A into centromeric chromatin requires a cooperative array of nucleosomal DNA contact sites. J Cell Biol. 1997 Feb 10;136(3):501-13. 9024683
  5. Muro Y, Azuma N, Onouchi H, Kunimatsu M, Tomita Y, Sasaki M, Sugimoto K: 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. 2000 Apr;120(1):218-23. 10759786
  6. Lomonte P, Sullivan KF, Everett RD: Degradation of nucleosome-associated centromeric histone H3-like protein CENP-A induced by herpes simplex virus type 1 protein ICP0. J Biol Chem. 2001 Feb 23;276(8):5829-35. Epub 2000 Oct 26. 11053442
  7. Zeitlin SG, Shelby RD, Sullivan KF: CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis. J Cell Biol. 2001 Dec 24;155(7):1147-57. Epub 2001 Dec 24. 11756469
  8. Kunitoku N, Sasayama T, Marumoto T, Zhang D, Honda S, Kobayashi O, Hatakeyama K, Ushio Y, Saya H, Hirota T: CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function. Dev Cell. 2003 Dec;5(6):853-64. 14667408
  9. Irvine DV, Amor DJ, Perry J, Sirvent N, Pedeutour F, Choo KH, Saffery R: Chromosome size and origin as determinants of the level of CENP-A incorporation into human centromeres. Chromosome Res. 2004;12(8):805-15. 15702419
  10. Sullivan BA, Karpen GH: Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin. Nat Struct Mol Biol. 2004 Nov;11(11):1076-83. Epub 2004 Oct 10. 15475964
  11. Black BE, Foltz DR, Chakravarthy S, Luger K, Woods VL Jr, Cleveland DW: Structural determinants for generating centromeric chromatin. Nature. 2004 Jul 29;430(6999):578-82. 15282608
  12. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. 17081983
  13. Foltz DR, Jansen LE, Black BE, Bailey AO, Yates JR 3rd, Cleveland DW: The human CENP-A centromeric nucleosome-associated complex. Nat Cell Biol. 2006 May;8(5):458-69. Epub 2006 Apr 16. 16622419
  14. Alonso A, Fritz B, Hasson D, Abrusan G, Cheung F, Yoda K, Radlwimmer B, Ladurner AG, Warburton PE: Co-localization of CENP-C and CENP-H to discontinuous domains of CENP-A chromatin at human neocentromeres. Genome Biol. 2007;8(7):R148. 17651496
  15. Slattery SD, Moore RV, Brinkley BR, Hall RM: Aurora-C and Aurora-B share phosphorylation and regulation of CENP-A and Borealin during mitosis. Cell Cycle. 2008 Mar 15;7(6):787-95. Epub 2008 Mar 4. 18239465
  16. Orthaus S, Biskup C, Hoffmann B, Hoischen C, Ohndorf S, Benndorf K, Diekmann S: Assembly of the inner kinetochore proteins CENP-A and CENP-B in living human cells. Chembiochem. 2008 Jan 4;9(1):77-92. 18072184
  17. Hellwig D, Munch S, Orthaus S, Hoischen C, Hemmerich P, Diekmann S: Live-cell imaging reveals sustained centromere binding of CENP-T via CENP-A and CENP-B. J Biophotonics. 2008 Aug;1(3):245-54. doi: 10.1002/jbio.200810014. 19412974
  18. Marshall OJ, Marshall AT, Choo KH: Three-dimensional localization of CENP-A suggests a complex higher order structure of centromeric chromatin. J Cell Biol. 2008 Dec 29;183(7):1193-202. doi: 10.1083/jcb.200804078. 19114591
  19. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  20. Foltz DR, Jansen LE, Bailey AO, Yates JR 3rd, Bassett EA, Wood S, Black BE, Cleveland DW: Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP. Cell. 2009 May 1;137(3):472-84. doi: 10.1016/j.cell.2009.02.039. 19410544
  21. Dunleavy EM, Roche D, Tagami H, Lacoste N, Ray-Gallet D, Nakamura Y, Daigo Y, Nakatani Y, Almouzni-Pettinotti G: HJURP is a cell-cycle-dependent maintenance and deposition factor of CENP-A at centromeres. Cell. 2009 May 1;137(3):485-97. doi: 10.1016/j.cell.2009.02.040. 19410545
  22. Kim H, Lee M, Lee S, Park B, Koh W, Lee DJ, Lim DS, Lee S: Cancer-upregulated gene 2 (CUG2), a new component of centromere complex, is required for kinetochore function. Mol Cells. 2009 Jun 30;27(6):697-701. doi: 10.1007/s10059-009-0083-2. Epub 2009 Jun 12. 19533040
  23. Carroll CW, Silva MC, Godek KM, Jansen LE, Straight AF: Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N. Nat Cell Biol. 2009 Jul;11(7):896-902. doi: 10.1038/ncb1899. Epub 2009 Jun 21. 19543270
  24. Trazzi S, Perini G, Bernardoni R, Zoli M, Reese JC, Musacchio A, Della Valle G: The C-terminal domain of CENP-C displays multiple and critical functions for mammalian centromere formation. PLoS One. 2009 Jun 8;4(6):e5832. doi: 10.1371/journal.pone.0005832. 19503796
  25. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
  26. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  27. Sekulic N, Bassett EA, Rogers DJ, Black BE: The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres. Nature. 2010 Sep 16;467(7313):347-51. doi: 10.1038/nature09323. Epub 2010 Aug 25. 20739937
  28. Hu H, Liu Y, Wang M, Fang J, Huang H, Yang N, Li Y, Wang J, Yao X, Shi Y, Li G, Xu RM: Structure of a CENP-A-histone H4 heterodimer in complex with chaperone HJURP. Genes Dev. 2011 May 1;25(9):901-6. doi: 10.1101/gad.2045111. Epub 2011 Apr 8. 21478274