H2AX_XENLA
ID H2AX_XENLA Reviewed; 139 AA.
AC Q6GM86;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Histone H2AX;
DE Short=H2a/x;
DE AltName: Full=Histone H2A.X;
GN Name=h2ax;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PHOSPHORYLATION AT SER-136.
RX PubMed=10477747; DOI=10.1083/jcb.146.5.905;
RA Rogakou E.P., Boon C., Redon C., Bonner W.M.;
RT "Megabase chromatin domains involved in DNA double-strand breaks in vivo.";
RL J. Cell Biol. 146:905-916(1999).
RN [3]
RP PHOSPHORYLATION AT TYR-139.
RX PubMed=19092802; DOI=10.1038/nature07668;
RA Xiao A., Li H., Shechter D., Ahn S.H., Fabrizio L.A., Erdjument-Bromage H.,
RA Ishibe-Murakami S., Wang B., Tempst P., Hofmann K., Patel D.J.,
RA Elledge S.J., Allis C.D.;
RT "WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase
RT activity.";
RL Nature 457:57-62(2009).
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|UniProtKB:P16104}.
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-136 (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-136 (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-136 is required
CC for DNA DSB repair. Phosphorylation at Tyr-139 (H2AXY142ph) by
CC baz1b/wstf determines the relative recruitment of either DNA repair or
CC pro-apoptotic factors. Phosphorylation at Tyr-139 (H2AXY142ph) favors
CC the recruitment of pro-apoptosis factors. In contrast,
CC dephosphorylation of Tyr-139 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-136 (H2AX139ph).
CC {ECO:0000269|PubMed:10477747, ECO:0000269|PubMed:19092802}.
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|UniProtKB:P16104}.
CC -!- SIMILARITY: Belongs to the histone H2A family. {ECO:0000305}.
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DR EMBL; BC074188; AAH74188.1; -; mRNA.
DR RefSeq; XP_018097505.1; XM_018242016.1.
DR AlphaFoldDB; Q6GM86; -.
DR SMR; Q6GM86; -.
DR BioGRID; 102691; 4.
DR iPTMnet; Q6GM86; -.
DR PRIDE; Q6GM86; -.
DR DNASU; 444528; -.
DR GeneID; 444528; -.
DR KEGG; xla:444528; -.
DR CTD; 444528; -.
DR Xenbase; XB-GENE-5719408; h2ax.S.
DR OrthoDB; 1504122at2759; -.
DR Proteomes; UP000186698; Chromosome 7S.
DR Bgee; 444528; Expressed in neurula embryo and 19 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; IEA:UniProtKB-KW.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:InterPro.
DR GO; GO:0030527; F:structural constituent of chromatin; IEA:InterPro.
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 1: Evidence at protein 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|UniProtKB:P16104"
FT CHAIN 2..139
FT /note="Histone H2AX"
FT /id="PRO_0000055245"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 136..137
FT /note="[ST]-Q motif"
FT COMPBIAS 120..139
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P16104"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16104"
FT MOD_RES 10
FT /note="N6-lactoyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P0C0S5"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10477747"
FT MOD_RES 139
FT /note="Phosphotyrosine; by WSTF"
FT /evidence="ECO:0000269|PubMed:19092802"
FT CROSSLNK 14
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P16104"
FT CROSSLNK 16
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P16104"
FT CROSSLNK 120
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P16104"
SQ SEQUENCE 139 AA; 14855 MW; 0E1226286A4A0E4D CRC64;
MSGRGKAVSK TRAKAKTRSS RAGLQFPVGR VHRLLRKGNY AHRVGAGAPV YLAAVLEYLT
AEILELAGNA ARDNKKSRII PRHLQLAVRN DEELNKLLGG VTIAQGGVLP NIQAVLLPKK
SSGGVSTSGK KSSQQSQEY
