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Protein

Histone H2AX

Gene

h2afx

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-DRE-201722. Formation of the beta-catenin:TCF transactivating complex.
R-DRE-212300. PRC2 methylates histones and DNA.
R-DRE-2299718. Condensation of Prophase Chromosomes.
R-DRE-2559580. Oxidative Stress Induced Senescence.
R-DRE-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-DRE-3214815. HDACs deacetylate histones.
R-DRE-3214858. RMTs methylate histone arginines.
R-DRE-427359. SIRT1 negatively regulates rRNA Expression.
R-DRE-427413. NoRC negatively regulates rRNA expression.
R-DRE-5250924. B-WICH complex positively regulates rRNA expression.
R-DRE-5578749. Transcriptional regulation by small RNAs.
R-DRE-5625886. Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3.
R-DRE-5689603. UCH proteinases.
R-DRE-5689880. Ub-specific processing proteases.
R-DRE-5689901. Metalloprotease DUBs.
R-DRE-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-DRE-5693571. Nonhomologous End-Joining (NHEJ).
R-DRE-5693607. Processing of DNA double-strand break ends.
R-DRE-606279. Deposition of new CENPA-containing nucleosomes at the centromere.
R-DRE-69473. G2/M DNA damage checkpoint.
R-DRE-73728. RNA Polymerase I Promoter Opening.
R-DRE-73777. RNA Polymerase I Chain Elongation.
R-DRE-8936459. RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
R-DRE-8939236. RUNX1 regulates transcription of genes involved in differentiation of HSCs.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone H2AX
Short name:
H2a/x
Alternative name(s):
Histone H2A.X
Gene namesi
Name:h2afx
ORF Names:zgc:56329
OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)
Taxonomic identifieri7955 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
Proteomesi
  • UP000000437 Componenti: Chromosome 5

Organism-specific databases

ZFINiZDB-GENE-040426-987. 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000552442 – 142Histone H2AXAdd BLAST141

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei2PhosphoserineBy similarity1
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
Cross-linki120Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei139PhosphoserineBy similarity1
Modified residuei142Phosphotyrosine; by WSTFBy similarity1

Post-translational modificationi

Phosphorylated. Phosphorylation of Ser-139 (H2AX139ph) occurs in response to DNA double strand breaks (DSBs) generated by exogenous genotoxic agents, by stalled replication forks and by meiotic recombination events. Phosphorylation is dependent on the DNA damage checkpoint kinases ATR and ATM, spreads on either side of a detected DSB site 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. Dephosphorylation of Ser-139 is required for DNA DSB repair. Phosphorylation at Tyr-142 (H2AXY142ph) by baz1b/wstf determines the relative recruitment of either DNA repair or pro-apoptotic factors. Phosphorylation at Tyr-142 (H2AXY142ph) favors the recruitment of pro-apoptosis factors. In contrast, dephosphorylation of Tyr-142 by EYA proteins (eya1, eya2, eya3 or eya4) favors the recruitment of MDC1-containing DNA repair complexes to the tail of phosphorylated Ser-139 (H2AX139ph).
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

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ7ZUY3.
PRIDEiQ7ZUY3.

Expressioni

Gene expression databases

BgeeiENSDARG00000029406.

Interactioni

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. Interacts with numerous proteins required for DNA damage signaling and repair when phosphorylated on Ser-139 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi7955.ENSDARP00000040327.

Structurei

3D structure databases

ProteinModelPortaliQ7ZUY3.
SMRiQ7ZUY3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi139 – 140[ST]-Q motif2

Domaini

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.
GeneTreeiENSGT00760000118934.
HOGENOMiHOG000234652.
HOVERGENiHBG009342.
InParanoidiQ7ZUY3.
KOiK11251.
OMAiRIVPCHI.
OrthoDBiEOG091G0XGD.
PhylomeDBiQ7ZUY3.
TreeFamiTF300137.

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.
PRINTSiPR00620. HISTONEH2A.
SMARTiView protein in SMART
SM00414. H2A. 1 hit.
SUPFAMiSSF47113. SSF47113. 1 hit.
PROSITEiView protein in PROSITE
PS00046. HISTONE_H2A. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q7ZUY3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGRGKTGGK ARAKAKTRSS RAGLQFPVGR VHRLLRKGNY AERVGAGAPV
60 70 80 90 100
YLAAVLEYLT AEILELAGNA ARDNKKTRII PRHLQLAVRN DEELNKLLGG
110 120 130 140
VTIAQGGVLP NIQAVLLPKK TGQAAASSGK SGKKGSSQSQ EY
Length:142
Mass (Da):15,001
Last modified:January 23, 2007 - v3
Checksum:i5D50FE6CEF4E98C9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC046078 mRNA. Translation: AAH46078.1.
RefSeqiNP_957367.1. NM_201073.1.
UniGeneiDr.114938.

Genome annotation databases

EnsembliENSDART00000040328; ENSDARP00000040327; ENSDARG00000029406.
GeneIDi394048.
KEGGidre:394048.

Similar proteinsi

Entry informationi

Entry nameiH2AX_DANRE
AccessioniPrimary (citable) accession number: Q7ZUY3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: January 23, 2007
Last modified: September 27, 2017
This is version 114 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families