H2AX_DANRE
ID H2AX_DANRE Reviewed; 142 AA.
AC Q7ZUY3;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Histone H2AX;
DE Short=H2a/x;
DE AltName: Full=Histone H2A.X;
GN Name=h2ax; ORFNames=zgc:56329;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Variant histone H2A which replaces conventional H2A in a
CC subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin,
CC limiting DNA accessibility to the cellular machineries which require
CC DNA as a template. Histones thereby play a central role in
CC transcription regulation, DNA repair, DNA replication and chromosomal
CC stability. DNA accessibility is regulated via a complex set of post-
CC translational modifications of histones, also called histone code, and
CC nucleosome remodeling. Required for checkpoint-mediated arrest of cell
CC cycle progression in response to low doses of ionizing radiation and
CC for efficient repair of DNA double strand breaks (DSBs) specifically
CC when modified by C-terminal phosphorylation (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: The nucleosome is a histone octamer containing two molecules
CC each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and
CC two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of
CC DNA. Interacts with numerous proteins required for DNA damage signaling
CC and repair when phosphorylated on Ser-139 (By similarity).
CC {ECO:0000250|UniProtKB:P16104}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P27661}.
CC Chromosome {ECO:0000250|UniProtKB:P27661}.
CC -!- DOMAIN: The [ST]-Q motif constitutes a recognition sequence for kinases
CC from the PI3/PI4-kinase family.
CC -!- PTM: Phosphorylated. Phosphorylation of Ser-139 (H2AX139ph) occurs in
CC response to DNA double strand breaks (DSBs) generated by exogenous
CC genotoxic agents, by stalled replication forks and by meiotic
CC recombination events. Phosphorylation is dependent on the DNA damage
CC checkpoint kinases ATR and ATM, spreads on either side of a detected
CC DSB site and may mark the surrounding chromatin for recruitment of
CC proteins required for DNA damage signaling and repair. Widespread
CC phosphorylation may also serve to amplify the damage signal or aid
CC repair of persistent lesions. Dephosphorylation of Ser-139 is required
CC for DNA DSB repair. Phosphorylation at Tyr-142 (H2AXY142ph) by
CC baz1b/wstf determines the relative recruitment of either DNA repair or
CC pro-apoptotic factors. Phosphorylation at Tyr-142 (H2AXY142ph) favors
CC the recruitment of pro-apoptosis factors. In contrast,
CC dephosphorylation of Tyr-142 by EYA proteins (eya1, eya2, eya3 or eya4)
CC favors the recruitment of MDC1-containing DNA repair complexes to the
CC tail of phosphorylated Ser-139 (H2AX139ph).
CC -!- PTM: Monoubiquitination of Lys-120 (H2AXK119ub) by ring1 and rnf2/ring2
CC complex gives a specific tag for epigenetic transcriptional repression.
CC Following DNA double-strand breaks (DSBs), it is ubiquitinated through
CC 'Lys-63' linkage of ubiquitin moieties by the E2 ligase ube2n and the
CC E3 ligases rnf8 and rnf168, leading to the recruitment of repair
CC proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16
CC (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is
CC initiated by rnf168 that mediates monoubiquitination at these 2 sites,
CC and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin;
CC rnf8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro.
CC H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination
CC (H2AK13Ub and H2AK15Ub) are distinct events (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the histone H2A family. {ECO:0000305}.
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DR EMBL; BC046078; AAH46078.1; -; mRNA.
DR RefSeq; NP_957367.1; NM_201073.1.
DR AlphaFoldDB; Q7ZUY3; -.
DR SMR; Q7ZUY3; -.
DR STRING; 7955.ENSDARP00000040327; -.
DR PaxDb; Q7ZUY3; -.
DR Ensembl; ENSDART00000040328; ENSDARP00000040327; ENSDARG00000029406.
DR GeneID; 394048; -.
DR KEGG; dre:394048; -.
DR CTD; 3014; -.
DR ZFIN; ZDB-GENE-040426-987; h2ax.
DR eggNOG; KOG1756; Eukaryota.
DR GeneTree; ENSGT01020000230360; -.
DR HOGENOM; CLU_062828_3_1_1; -.
DR InParanoid; Q7ZUY3; -.
DR OMA; CCVVAIT; -.
DR OrthoDB; 1504122at2759; -.
DR PhylomeDB; Q7ZUY3; -.
DR TreeFam; TF300137; -.
DR Reactome; R-DRE-110330; Recognition and association of DNA glycosylase with site containing an affected purine.
DR Reactome; R-DRE-110331; Cleavage of the damaged purine.
DR Reactome; R-DRE-171306; Packaging Of Telomere Ends.
DR Reactome; R-DRE-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-DRE-212300; PRC2 methylates histones and DNA.
DR Reactome; R-DRE-2299718; Condensation of Prophase Chromosomes.
DR Reactome; R-DRE-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-DRE-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-DRE-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-DRE-3214815; HDACs deacetylate histones.
DR Reactome; R-DRE-3214847; HATs acetylate histones.
DR Reactome; R-DRE-3214858; RMTs methylate histone arginines.
DR Reactome; R-DRE-427359; SIRT1 negatively regulates rRNA expression.
DR Reactome; R-DRE-5250924; B-WICH complex positively regulates rRNA expression.
DR Reactome; R-DRE-5578749; Transcriptional regulation by small RNAs.
DR Reactome; R-DRE-5625886; Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3.
DR Reactome; R-DRE-5689603; UCH proteinases.
DR Reactome; R-DRE-5689880; Ub-specific processing proteases.
DR Reactome; R-DRE-5689901; Metalloprotease DUBs.
DR Reactome; R-DRE-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-DRE-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-DRE-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-DRE-606279; Deposition of new CENPA-containing nucleosomes at the centromere.
DR Reactome; R-DRE-68616; Assembly of the ORC complex at the origin of replication.
DR Reactome; R-DRE-69473; G2/M DNA damage checkpoint.
DR Reactome; R-DRE-73728; RNA Polymerase I Promoter Opening.
DR Reactome; R-DRE-73772; RNA Polymerase I Promoter Escape.
DR Reactome; R-DRE-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR Reactome; R-DRE-9018519; Estrogen-dependent gene expression.
DR Reactome; R-DRE-9670095; Inhibition of DNA recombination at telomere.
DR PRO; PR:Q7ZUY3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 5.
DR Bgee; ENSDARG00000029406; Expressed in granulocyte and 27 other tissues.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR GO; GO:0000786; C:nucleosome; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:InterPro.
DR GO; GO:0030527; F:structural constituent of chromatin; IEA:InterPro.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:ZFIN.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR CDD; cd00074; H2A; 1.
DR Gene3D; 1.10.20.10; -; 1.
DR InterPro; IPR009072; Histone-fold.
DR InterPro; IPR002119; Histone_H2A.
DR InterPro; IPR007125; Histone_H2A/H2B/H3.
DR InterPro; IPR032454; Histone_H2A_C.
DR InterPro; IPR032458; Histone_H2A_CS.
DR PANTHER; PTHR23430; PTHR23430; 1.
DR Pfam; PF00125; Histone; 1.
DR Pfam; PF16211; Histone_H2A_C; 1.
DR PRINTS; PR00620; HISTONEH2A.
DR SMART; SM00414; H2A; 1.
DR SUPFAM; SSF47113; SSF47113; 1.
DR PROSITE; PS00046; HISTONE_H2A; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cell cycle; Chromosome; DNA damage; DNA recombination;
KW DNA repair; DNA-binding; Isopeptide bond; Meiosis; Nucleosome core;
KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250"
FT CHAIN 2..142
FT /note="Histone H2AX"
FT /id="PRO_0000055244"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 123..142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 139..140
FT /note="[ST]-Q motif"
FT COMPBIAS 124..142
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 10
FT /note="N6-lactoyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P0C0S5"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 142
FT /note="Phosphotyrosine; by WSTF"
FT /evidence="ECO:0000250"
FT CROSSLNK 14
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250"
FT CROSSLNK 16
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250"
FT CROSSLNK 120
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 142 AA; 15001 MW; 5D50FE6CEF4E98C9 CRC64;
MSGRGKTGGK ARAKAKTRSS RAGLQFPVGR VHRLLRKGNY AERVGAGAPV YLAAVLEYLT
AEILELAGNA ARDNKKTRII PRHLQLAVRN DEELNKLLGG VTIAQGGVLP NIQAVLLPKK
TGQAAASSGK SGKKGSSQSQ EY
