Histone H2AX

NameHistone H2AX
Synonyms
  • H2a/x
  • H2AX
  • Histone H2A.X
Gene NameH2AFX
OrganismHuman
Amino acid sequence
>lcl|BSEQ0013494|Histone H2AX
MSGRGKTGGKARAKAKSRSSRAGLQFPVGRVHRLLRKGHYAERVGAGAPVYLAAVLEYLT
AEILELAGNAARDNKKTRIIPRHLQLAIRNDEELNKLLGGVTIAQGGVLPNIQAVLLPKK
TSATVGPKAPSGGKKATQASQEY
Number of residues143
Molecular Weight15144.45
Theoretical pINot Available
GO Classification
Functions
  • enzyme binding
  • damaged DNA binding
  • histone binding
  • DNA binding
Processes
  • cerebral cortex development
  • DNA repair
  • chromatin organization
  • positive regulation of DNA repair
  • cellular senescence
  • chromatin silencing
  • DNA damage checkpoint
  • cellular response to DNA damage stimulus
  • double-strand break repair
  • meiotic cell cycle
  • double-strand break repair via homologous recombination
  • cellular response to gamma radiation
  • double-strand break repair via nonhomologous end joining
  • nucleosome assembly
  • response to ionizing radiation
  • spermatogenesis
  • viral process
Components
  • nucleus
  • replication fork
  • extracellular exosome
  • nucleoplasm
  • condensed nuclear chromosome
  • male germ cell nucleus
  • nucleosome
  • nuclear chromatin
  • site of double-strand break
  • XY body
General FunctionHistone binding
Specific FunctionVariant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Required for checkpoint-mediated arrest of cell cycle progression in response to low doses of ionizing radiation and for efficient repair of DNA double strand breaks (DSBs) specifically when modified by C-terminal phosphorylation.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP16104
UniProtKB Entry NameH2AX_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0013495|Histone H2AX (H2AFX)
ATGTCGGGCCGCGGCAAGACTGGCGGCAAGGCCCGCGCCAAGGCCAAGTCGCGCTCGTCG
CGCGCCGGCCTCCAGTTCCCAGTGGGCCGTGTACACCGGCTGCTGCGGAAGGGCCACTAC
GCCGAGCGCGTTGGCGCCGGCGCGCCAGTGTACCTGGCGGCAGTGCTGGAGTACCTCACC
GCTGAGATCCTGGAGCTGGCGGGCAATGCGGCCCGCGACAACAAGAAGACGCGAATCATC
CCCCGCCACCTGCAGCTGGCCATCCGCAACGACGAGGAGCTCAACAAGCTGCTGGGCGGC
GTGACGATCGCCCAGGGAGGCGTCCTGCCCAACATCCAGGCCGTGCTGCTGCCCAAGAAG
ACCAGCGCCACCGTGGGGCCGAAGGCGCCCTCGGGCGGCAAGAAGGCCACCCAGGCCTCC
CAGGAGTACTAA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:4739
Chromosome Location11
LocusNot Available
References
  1. Mannironi C, Bonner WM, Hatch CL: H2A.X. a histone isoprotein with a conserved C-terminal sequence, is encoded by a novel mRNA with both DNA replication type and polyA 3' processing signals. Nucleic Acids Res. 1989 Nov 25;17(22):9113-26. 2587254
  2. 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
  3. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM: DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 1998 Mar 6;273(10):5858-68. 9488723
  4. Rogakou EP, Boon C, Redon C, Bonner WM: Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol. 1999 Sep 6;146(5):905-16. 10477747
  5. Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM: A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol. 2000 Jul 27-Aug 10;10(15):886-95. 10959836
  6. Rogakou EP, Nieves-Neira W, Boon C, Pommier Y, Bonner WM: Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. J Biol Chem. 2000 Mar 31;275(13):9390-5. 10734083
  7. Ward IM, Chen J: Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem. 2001 Dec 21;276(51):47759-62. Epub 2001 Oct 22. 11673449
  8. Kobayashi J, Tauchi H, Sakamoto S, Nakamura A, Morishima K, Matsuura S, Kobayashi T, Tamai K, Tanimoto K, Komatsu K: NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain. Curr Biol. 2002 Oct 29;12(21):1846-51. 12419185
  9. Ward IM, Minn K, Jorda KG, Chen J: Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX. J Biol Chem. 2003 May 30;278(22):19579-82. Epub 2003 Apr 15. 12697768
  10. Furuta T, Takemura H, Liao ZY, Aune GJ, Redon C, Sedelnikova OA, Pilch DR, Rogakou EP, Celeste A, Chen HT, Nussenzweig A, Aladjem MI, Bonner WM, Pommier Y: Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes. J Biol Chem. 2003 May 30;278(22):20303-12. Epub 2003 Mar 25. 12660252
  11. Stewart GS, Wang B, Bignell CR, Taylor AM, Elledge SJ: MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature. 2003 Feb 27;421(6926):961-6. 12607005
  12. Park EJ, Chan DW, Park JH, Oettinger MA, Kwon J: DNA-PK is activated by nucleosomes and phosphorylates H2AX within the nucleosomes in an acetylation-dependent manner. Nucleic Acids Res. 2003 Dec 1;31(23):6819-27. 14627815
  13. Stiff T, O'Driscoll M, Rief N, Iwabuchi K, Lobrich M, Jeggo PA: ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer Res. 2004 Apr 1;64(7):2390-6. 15059890
  14. Lukas C, Melander F, Stucki M, Falck J, Bekker-Jensen S, Goldberg M, Lerenthal Y, Jackson SP, Bartek J, Lukas J: Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-dependent chromatin retention. EMBO J. 2004 Jul 7;23(13):2674-83. Epub 2004 Jun 17. 15201865
  15. Kurz EU, Douglas P, Lees-Miller SP: Doxorubicin activates ATM-dependent phosphorylation of multiple downstream targets in part through the generation of reactive oxygen species. J Biol Chem. 2004 Dec 17;279(51):53272-81. Epub 2004 Oct 14. 15489221
  16. Mischo HE, Hemmerich P, Grosse F, Zhang S: Actinomycin D induces histone gamma-H2AX foci and complex formation of gamma-H2AX with Ku70 and nuclear DNA helicase II. J Biol Chem. 2005 Mar 11;280(10):9586-94. Epub 2004 Dec 21. 15613478
  17. Chowdhury D, Keogh MC, Ishii H, Peterson CL, Buratowski S, Lieberman J: gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair. Mol Cell. 2005 Dec 9;20(5):801-9. Epub 2005 Nov 28. 16310392
  18. Neuhaus EM, Mashukova A, Barbour J, Wolters D, Hatt H: Novel function of beta-arrestin2 in the nucleus of mature spermatozoa. J Cell Sci. 2006 Aug 1;119(Pt 15):3047-56. Epub 2006 Jul 4. 16820410
  19. Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, Lukas J: RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell. 2007 Nov 30;131(5):887-900. Epub 2007 Nov 20. 18001824
  20. Huen MS, Grant R, Manke I, Minn K, Yu X, Yaffe MB, Chen J: RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell. 2007 Nov 30;131(5):901-14. Epub 2007 Nov 20. 18001825
  21. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007 May 25;316(5828):1160-6. 17525332
  22. Stewart GS, Panier S, Townsend K, Al-Hakim AK, Kolas NK, Miller ES, Nakada S, Ylanko J, Olivarius S, Mendez M, Oldreive C, Wildenhain J, Tagliaferro A, Pelletier L, Taubenheim N, Durandy A, Byrd PJ, Stankovic T, Taylor AM, Durocher D: The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Cell. 2009 Feb 6;136(3):420-34. doi: 10.1016/j.cell.2008.12.042. 19203578
  23. Doil C, Mailand N, Bekker-Jensen S, Menard P, Larsen DH, Pepperkok R, Ellenberg J, Panier S, Durocher D, Bartek J, Lukas J, Lukas C: RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell. 2009 Feb 6;136(3):435-46. doi: 10.1016/j.cell.2008.12.041. 19203579
  24. Xiao A, Li H, Shechter D, Ahn SH, Fabrizio LA, Erdjument-Bromage H, Ishibe-Murakami S, Wang B, Tempst P, Hofmann K, Patel DJ, Elledge SJ, Allis CD: WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity. Nature. 2009 Jan 1;457(7225):57-62. doi: 10.1038/nature07668. Epub 2008 Dec 17. 19092802
  25. Cook PJ, Ju BG, Telese F, Wang X, Glass CK, Rosenfeld MG: Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions. Nature. 2009 Apr 2;458(7238):591-6. doi: 10.1038/nature07849. Epub 2009 Feb 22. 19234442
  26. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  27. 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
  28. Mattiroli F, Vissers JH, van Dijk WJ, Ikpa P, Citterio E, Vermeulen W, Marteijn JA, Sixma TK: RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling. Cell. 2012 Sep 14;150(6):1182-95. doi: 10.1016/j.cell.2012.08.005. 22980979
  29. Jha HC, A J MP, Saha A, Banerjee S, Lu J, Robertson ES: Epstein-Barr virus essential antigen EBNA3C attenuates H2AX expression. J Virol. 2014 Apr;88(7):3776-88. doi: 10.1128/JVI.03568-13. Epub 2014 Jan 15. 24429368
  30. Hendriks IA, D'Souza RC, Yang B, Verlaan-de Vries M, Mann M, Vertegaal AC: Uncovering global SUMOylation signaling networks in a site-specific manner. Nat Struct Mol Biol. 2014 Oct;21(10):927-36. doi: 10.1038/nsmb.2890. Epub 2014 Sep 14. 25218447
  31. Shao Z, Li F, Sy SM, Yan W, Zhang Z, Gong D, Wen B, Huen MS, Gong Q, Wu J, Shi Y: Specific recognition of phosphorylated tail of H2AX by the tandem BRCT domains of MCPH1 revealed by complex structure. J Struct Biol. 2012 Feb;177(2):459-68. doi: 10.1016/j.jsb.2011.11.022. Epub 2011 Dec 1. 22154951