Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Histone H2AX



Mus musculus (Mouse)
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli


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.15 Publications


Haploinsufficient for the suppression of genomic instability. This phenotype is further exacerbated in the absence of TP53.

GO - Molecular functioni

GO - Biological processi

  • cellular response to DNA damage stimulus Source: MGI
  • chromatin silencing Source: GO_Central
  • DNA repair Source: MGI
  • double-strand break repair via homologous recombination Source: MGI
  • meiotic cell cycle Source: UniProtKB-KW
  • spermatogenesis Source: MGI


Molecular functionDNA-binding
Biological processCell cycle, DNA damage, DNA recombination, DNA repair, Meiosis

Enzyme and pathway databases

ReactomeiR-MMU-1221632. Meiotic synapsis.
R-MMU-1221633. Meiotic Synapsis.
R-MMU-427389. ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression.
R-MMU-427413. NoRC negatively regulates rRNA expression.
R-MMU-5334118. DNA methylation.
R-MMU-5617472. Activation of anterior HOX genes in hindbrain development during early embryogenesis.
R-MMU-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-MMU-5693571. Nonhomologous End-Joining (NHEJ).
R-MMU-5693607. Processing of DNA double-strand break ends.
R-MMU-573389. NoRC negatively regulates rRNA expression.
R-MMU-69473. G2/M DNA damage checkpoint.
R-MMU-912446. Meiotic recombination.
R-MMU-912497. Meiotic Recombination.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone H2AX
Short name:
Alternative name(s):
Histone H2A.X
Gene namesi
Synonyms:H2a.x, H2ax, Hist5-2ax
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:102688. H2afx.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleosome core, Nucleus

Pathology & Biotechi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi6K → A: No effect on radiosensitivity; when associated with A-10, A-14 and A-16. 1 Publication1
Mutagenesisi10K → A: No effect on radiosensitivity; when associated with A-6, A-14 and A-16. 1 Publication1
Mutagenesisi14K → A: No effect on radiosensitivity; when associated with A-6, A-10 and A-16. 1 Publication1
Mutagenesisi16K → A: No effect on radiosensitivity; when associated with A-6, A-10 and A-14. 1 Publication1
Mutagenesisi37K → A: Increased radiosensitivity. No effect on phosphorylation after DNA damage. No effect on Ser-140 phosphorylation, nor on TP53BP1 recruitment to DNA double-strand breaks. 1 Publication1
Mutagenesisi37K → R: No effect on phosphorylation after DNA damage, but increased radiosensitivity. Further increase in radiosensitivity; when associated with A-140. 1 Publication1
Mutagenesisi119 – 120KK → AA: Complete loss of ubiquitination and increased radiosensitivity. 1 Publication2
Mutagenesisi137S → A: Increased genomic instability and radiosensitivity; when associated with A-140. 1 Publication1
Mutagenesisi140S → A: Increased genomic instability and radiosensitivity; when associated with A-137. Reduced homologous recombination. No effect on Lys-40 acetylation. Further increase in radiosensitivity; when associated with R-37. 3 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000552432 – 143Histone H2AXAdd BLAST142

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserine1 Publication1
Modified residuei2Phosphoserine1 Publication1
Modified residuei6N6-acetyllysineCombined sources1
Modified residuei10N6-acetyllysineCombined sources1
Cross-linki14Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki16Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei37N6-acetyllysine; by CREBBP and EP3001 Publication1
Cross-linki120Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei121PhosphoserineCombined sources1
Modified residuei122PhosphoserineCombined sources1
Cross-linki128Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki135Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei137PhosphoserineCombined sources1
Modified residuei140Phosphoserine; by ATM, ATR and PRKDCCombined sources9 Publications1
Modified residuei143Phosphotyrosine; by WSTF1 Publication1

Post-translational modificationi

Phosphorylated on Ser-140 (to form gamma-H2AX or H2AX139ph) in response to DNA double strand breaks (DSBs) generated by exogenous genotoxic agents, by stalled replication forks, by meiotic recombination events and during immunoglobulin class switching in lymphocytes. Phosphorylation can extend up to several thousand nucleosomes from the actual site of the DSB and may mark the surrounding chromatin for recruitment of proteins required for DNA damage signaling and repair. Widespread phosphorylation may also serve to amplify the damage signal or aid repair of persistent lesions. Phosphorylation of Ser-140 (H2AX139ph) in response to ionizing radiation is mediated by both ATM and PRKDC while defects in DNA replication induce Ser-140 phosphorylation (H2AX139ph) subsequent to activation of ATR and PRKDC. Dephosphorylation of Ser-140 by PP2A is required for DNA DSB repair. In meiosis, Ser-140 phosphorylation (H2AX139ph) first occurs at synaptonemal complexes during leptotene and is an ATM-dependent response to the formation of programmed DSBs by SPO11. Ser-140 phosphorylation (H2AX139ph) subsequently occurs at unsynapsed regions of both autosomes and the XY bivalent during zygotene and is ATR- and BRCA1-dependent. Ser-140 phosphorylation (H2AX139ph) may also be required for transcriptional repression of unsynapsed chromatin and meiotic sex chromosome inactivation (MSCI), whereby the X and Y chromosomes condense in pachytene to form the heterochromatic XY-body. During immunoglobulin class switch recombination in lymphocytes, Ser-140 phosphorylation (H2AX139ph) at sites of DNA-recombination requires the activation-induced cytidine deaminase AICDA. Phosphorylation at Tyr-143 (H2AXY142ph) by BAZ1B/WSTF determines the relative recruitment of either DNA repair or pro-apoptotic factors. Phosphorylation at Tyr-143 (H2AXY142ph) favors the recruitment of APBB1/FE65 and pro-apoptosis factors such as MAPK8/JNK1, triggering apoptosis. In contrast, dephosphorylation of Tyr-143 by EYA proteins (EYA1, EYA2, EYA3 or EYA4) favors the recruitment of MDC1-containing DNA repair complexes to the tail of phosphorylated Ser-140 (H2AX139ph).11 Publications
Monoubiquitination of Lys-120 (H2AXK119ub) by RING1 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events (By similarity).By similarity
Acetylation at Lys-37 increases in S and G2 phases. This modification has been proposed to be important for DNA double-strand break repair (PubMed:20488183).2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases


PTM databases



Tissue specificityi

Most abundant in testis, thymus and spleen.1 Publication

Developmental stagei

Synthesized in G1 as well as in S-phase.

Gene expression databases

GenevisibleiP27661. MM.


Subunit structurei

The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. May interact with numerous proteins required for DNA damage signaling and repair when phosphorylated on Ser-140. These include MDC1, TP53BP1 and the MRN complex, composed of MRE11, RAD50, and NBN. Interaction with the MRN complex is likely mediated at least in part by NBN. May also interact with DHX9/NDHII when phosphorylated on Ser-140 and MCPH1 when phosphorylated at Ser-140 or Tyr-143.

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200313. 14 interactors.
IntActiP27661. 13 interactors.


3D structure databases


Family & Domainsi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi140 – 141[ST]-Q motif2


The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family.

Sequence similaritiesi

Belongs to the histone H2A family.Curated

Phylogenomic databases

eggNOGiKOG1756. Eukaryota.
COG5262. LUCA.

Family and domain databases

InterProiView protein in InterPro
IPR009072. Histone-fold.
IPR002119. Histone_H2A.
IPR007125. Histone_H2A/H2B/H3.
IPR032454. Histone_H2A_C.
IPR032458. Histone_H2A_CS.
PfamiView protein in Pfam
PF00125. Histone. 1 hit.
PF16211. Histone_H2A_C. 1 hit.
SMARTiView protein in SMART
SM00414. H2A. 1 hit.
SUPFAMiSSF47113. SSF47113. 1 hit.
PROSITEiView protein in PROSITE
PS00046. HISTONE_H2A. 1 hit.


Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P27661-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
60 70 80 90 100
110 120 130 140
Mass (Da):15,143
Last modified:January 23, 2007 - v2

Sequence databases

Select the link destinations:
Links Updated
X58069 mRNA. Translation: CAA41099.1.
Z35401 Genomic DNA. Translation: CAA84585.1.
BC005468 mRNA. Translation: AAH05468.1.
BC010336 mRNA. Translation: AAH10336.1.
RefSeqiNP_034566.1. NM_010436.2.

Genome annotation databases

EnsembliENSMUST00000052686; ENSMUSP00000051432; ENSMUSG00000049932.
UCSCiuc009pcy.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiH2AX_MOUSE
AccessioniPrimary (citable) accession number: P27661
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: September 27, 2017
This is version 171 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program


Keywords - Technical termi

Complete proteome, Reference proteome


  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families