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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

Complete GO annotation...

Keywords - Biological processi

Cell cycle, DNA damage, DNA recombination, DNA repair, Meiosis

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-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-69473. G2/M DNA damage checkpoint.

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleosome core, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 142141Histone H2AXPRO_0000055244Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei2 – 21PhosphoserineBy similarity
Cross-linki14 – 14Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki16 – 16Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki120 – 120Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei139 – 1391PhosphoserineBy similarity
Modified residuei142 – 1421Phosphotyrosine; by WSTFBy similarity

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

BgeeiQ7ZUY3.

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

Protein-protein interaction databases

STRINGi7955.ENSDARP00000040327.

Structurei

3D structure databases

ProteinModelPortaliQ7ZUY3.
SMRiQ7ZUY3. Positions 2-126.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi139 – 1402[ST]-Q motif

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.
OMAiANEMFIN.
OrthoDBiEOG7M0NTR.
PhylomeDBiQ7ZUY3.
TreeFamiTF300137.

Family and domain databases

Gene3Di1.10.20.10. 1 hit.
InterProiIPR009072. Histone-fold.
IPR002119. Histone_H2A.
IPR007125. Histone_H2A/H2B/H3.
IPR032454. Histone_H2A_C.
IPR032458. Histone_H2A_CS.
[Graphical view]
PfamiPF00125. Histone. 1 hit.
PF16211. Histone_H2A_C. 1 hit.
[Graphical view]
PRINTSiPR00620. HISTONEH2A.
SMARTiSM00414. H2A. 1 hit.
[Graphical view]
SUPFAMiSSF47113. SSF47113. 1 hit.
PROSITEiPS00046. HISTONE_H2A. 1 hit.
[Graphical view]

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.

Cross-referencesi

Sequence databases

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

3D structure databases

ProteinModelPortaliQ7ZUY3.
SMRiQ7ZUY3. Positions 2-126.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi7955.ENSDARP00000040327.

Proteomic databases

PaxDbiQ7ZUY3.
PRIDEiQ7ZUY3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3014.
ZFINiZDB-GENE-040426-987. h2afx.

Phylogenomic databases

eggNOGiKOG1756. Eukaryota.
COG5262. LUCA.
GeneTreeiENSGT00760000118934.
HOGENOMiHOG000234652.
HOVERGENiHBG009342.
InParanoidiQ7ZUY3.
KOiK11251.
OMAiANEMFIN.
OrthoDBiEOG7M0NTR.
PhylomeDBiQ7ZUY3.
TreeFamiTF300137.

Enzyme and pathway databases

ReactomeiR-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-69473. G2/M DNA damage checkpoint.

Miscellaneous databases

PROiQ7ZUY3.

Gene expression databases

BgeeiQ7ZUY3.

Family and domain databases

Gene3Di1.10.20.10. 1 hit.
InterProiIPR009072. Histone-fold.
IPR002119. Histone_H2A.
IPR007125. Histone_H2A/H2B/H3.
IPR032454. Histone_H2A_C.
IPR032458. Histone_H2A_CS.
[Graphical view]
PfamiPF00125. Histone. 1 hit.
PF16211. Histone_H2A_C. 1 hit.
[Graphical view]
PRINTSiPR00620. HISTONEH2A.
SMARTiSM00414. H2A. 1 hit.
[Graphical view]
SUPFAMiSSF47113. SSF47113. 1 hit.
PROSITEiPS00046. HISTONE_H2A. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. NIH - Zebrafish Gene Collection (ZGC) project
    Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].

Entry informationi

Entry nameiH2AX_DANRE
AccessioniPrimary (citable) accession number: Q7ZUY3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: January 23, 2007
Last modified: July 6, 2016
This is version 107 of the entry and version 3 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.