UniProt Accession

 H2AX_HUMAN; P16104; Q4ZGJ7; Q6IAS5 

Genbank Protein ID

 X14850; CR457079; DQ015918; BC004915; BC011694; BC013416 

Genbank Nucleotide ID

 CAA32968.1; CAG33360.1; AAY22178.1; AAH04915.1; AAH11694.1; AAH13416.1 

Protein Name

 Histone H2A.x 

Protein Synonyms/Alias

 H2a/x 

Gene Name

 H2AFX 

Gene Synonyms/Alias

 H2AX 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
6	**MSGRGKTGGKARA	acetylation	[1, 2, 3, 4]
10	GRGKTGGKARAKAKS	acetylation	[4]
96	RNDEELNKLLGGVTI	ubiquitination	[5]
119	IQAVLLPKKTSATVG	ubiquitination	[5, 6, 7, 8, 9, 10, 11, 12, 13, 14]
120	QAVLLPKKTSATVGP	ubiquitination	[5, 7, 8, 10, 11, 12, 13, 14, 15]
128	TSATVGPKAPSGGKK	ubiquitination	[5, 7, 8, 10, 12, 13, 14, 15]
134	PKAPSGGKKATQASQ	ubiquitination	[15]
135	KAPSGGKKATQASQE	ubiquitination	[5, 10]

Reference

 [1] Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase.
 Verreault A, Kaufman PD, Kobayashi R, Stillman B.
 Curr Biol. 1998 Jan 15;8(2):96-108. [PMID: 9427644]
 [2] Overlapping but distinct patterns of histone acetylation by the human coactivators p300 and PCAF within nucleosomal substrates.
 Schiltz RL, Mizzen CA, Vassilev A, Cook RG, Allis CD, Nakatani Y.
 J Biol Chem. 1999 Jan 15;274(3):1189-92. [PMID: 9880483]
 [3] DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics.
 Ikura T, Tashiro S, Kakino A, Shima H, Jacob N, Amunugama R, Yoder K, Izumi S, Kuraoka I, Tanaka K, Kimura H, Ikura M, Nishikubo S, Ito T, Muto A, Miyagawa K, Takeda S, Fishel R, Igarashi K, Kamiya K.
 Mol Cell Biol. 2007 Oct;27(20):7028-40. [PMID: 17709392]
 [4] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [6] A data set of human endogenous protein ubiquitination sites.
 Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
 Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
 [7] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [8] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [9] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [10] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [11] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [12] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [13] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [14] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [15] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 

Functional Description

 Variant 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. 

Sequence Annotation

 MOTIF 140 141 [ST]-Q motif.
 MOD_RES 2 2 N-acetylserine (By similarity).
 MOD_RES 2 2 Phosphoserine (By similarity).
 MOD_RES 37 37 N6-acetyllysine (By similarity).
 MOD_RES 140 140 Phosphoserine; by ATM, ATR and PRKDC.
 MOD_RES 143 143 Phosphotyrosine; by WSTF.
 CROSSLNK 14 14 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 16 16 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 120 120 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; Cell cycle; Chromosome; Complete proteome; DNA damage; DNA recombination; DNA repair; DNA-binding; Isopeptide bond; Meiosis; Nucleosome core; Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 143 AA 

Protein Sequence

Gene Ontology

 GO:0000794; C:condensed nuclear chromosome; IEA:Compara.
 GO:0001673; C:male germ cell nucleus; IEA:Compara.
 GO:0000790; C:nuclear chromatin; IEA:Compara.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0000786; C:nucleosome; NAS:UniProtKB.
 GO:0005657; C:replication fork; IEA:Compara.
 GO:0001741; C:XY body; IEA:Compara.
 GO:0003684; F:damaged DNA binding; IEA:Compara.
 GO:0003677; F:DNA binding; NAS:UniProtKB.
 GO:0000077; P:DNA damage checkpoint; IDA:UniProtKB.
 GO:0000724; P:double-strand break repair via homologous recombination; TAS:Reactome.
 GO:0007126; P:meiosis; IEA:UniProtKB-KW.
 GO:0006334; P:nucleosome assembly; NAS:UniProtKB.
 GO:0045739; P:positive regulation of DNA repair; NAS:UniProtKB.
 GO:0010212; P:response to ionizing radiation; NAS:UniProtKB.
 GO:0007283; P:spermatogenesis; IEA:Compara. 

Interpro

 IPR009072; Histone-fold.
 IPR007125; Histone_core_D.
 IPR002119; Histone_H2A. 

Pfam

 PF00125; Histone 

SMART

 SM00414; H2A 

PROSITE

 PS00046; HISTONE_H2A 

PRINTS

 PR00620; HISTONEH2A.