H2AX a histone that replaces conventional H2A in a subset of nucleosomes. 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. Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called 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. Phosphorylated on S139 by ATM and DNA-PK in response to DNA double strand breaks (DSBs) generated by exogenous genotoxic agents and by stalled replication forks, and may also occur during meiotic recombination events and 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. Dephosphorylation of S139 by PP2A is required for DNA DSB repair. Apparently phosphorylated on Y143 by WSTF, determining the relative recruitment of either DNA repair or pro-apoptotic factors. H2AXpY142 favors the recruitment of pro-apoptotic factors APBB1 and JNK1. In contrast, dephosphorylation of pY143 by EYA phosphatases favors the recruitment of MDC1-containing DNA repair complexes to the tail of phosphorylated pS139. Monoubiquitination of K119 by RING1 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'K63' linkages by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Note: This description may include information from UniProtKB.
Protein type: DNA repair, damage; DNA-binding; Helicase
Chromosomal Location of Human Ortholog: 11q23.3
Cellular Component:  centrosome; condensed nuclear chromosome; male germ cell nucleus; nuclear speck; nucleoplasm; nucleosome; nucleus; replication fork; site of DNA damage; site of double-strand break; XY body
Molecular Function:  damaged DNA binding; DNA binding; enzyme binding; histone binding; protein binding; protein heterodimerization activity
Biological Process:  cellular response to DNA damage stimulus; cellular response to gamma radiation; cellular senescence; cerebral cortex development; DNA damage checkpoint; double-strand break repair; double-strand break repair via homologous recombination; double-strand break repair via nonhomologous end joining; meiotic cell cycle; nucleosome assembly; positive regulation of DNA repair; response to ionizing radiation; spermatogenesis; viral process
Reference #:  P16104 (UniProtKB)
Alt. Names/Synonyms: H2A histone family, member X; H2A.X; H2a/x; H2AFX; H2AX; H2AX histone; Histone H2A.x; Histone H2AX
Gene Symbols: H2AFX
Molecular weight: 15,013 Da
Basal Isoelectric point: 10.74  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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H2AX

Protein Structure Not Found.


Cross-references to other databases:  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene