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    H2AFX H2A histone family member X [ Homo sapiens (human) ]

    Gene ID: 3014, updated on 19-Jul-2016
    Official Symbol
    H2AFXprovided by HGNC
    Official Full Name
    H2A histone family member Xprovided by HGNC
    Primary source
    HGNC:HGNC:4739
    See related
    Ensembl:ENSG00000188486 HPRD:03465; MIM:601772; Vega:OTTHUMG00000166196
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    H2AX; H2A.X; H2A/X
    Summary
    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. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene encodes a replication-independent histone that is a member of the histone H2A family, and generates two transcripts through the use of the conserved stem-loop termination motif, and the polyA addition motif. [provided by RefSeq, Oct 2015]
    Orthologs
    Location:
    11q23.3
    Exon count:
    1
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 11 NC_000011.10 (119093874..119095467, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (118964580..118966177, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene VPS11, CORVET/HOPS core subunit Neighboring gene hydroxymethylbilane synthase Neighboring gene dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 Neighboring gene uncharacterized LOC107984397 Neighboring gene C2CD2 like

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat peptides bind core histones H2A, H2B, H3 and H4, and Tat protein recruits histone acetyltransferases to the HIV-1 LTR promoter leading to acetylation of histones H3 and H4, derepressing chromatin structure and increasing NFkappaB responsiveness PubMed
    Vpr vpr Soluble HIV-1 Vpr induces a DNA damage response by forming H2AX- and 53BP1-containing DNA repair foci PubMed
    vpr HIV-1 Vpr expression in HeLa cells and human primary CD4+ lymphocytes induces phosphorylation of H2AFX and formation of nuclear foci containing H2AFX and BRCA1 PubMed
    vpr Recruitment of a catalytically active CRL4A (VPRBP) complex is required to observe HIV-1 Vpr-interacting unknown cellular ubiquitinated proteins. Phosphorylation of H2AX requires Vpr-induced K48 residue polyubiquitination PubMed
    vpr HIV-1 Vpr binds DCAF1 and activates the DNA damage response in renal tubule epithelial cells, in which gamma H2AX-positive nuclei are abundant compared to the control PubMed
    integrase gag-pol HIV-1 IN-mediated proviral DNA integration triggers cell death during HIV-1 infection. The mechanism of killing during viral integration involves activation of DNA-PK, which causes phosphorylation of p53 and histone gammaH2AX PubMed

    Go to the HIV-1, Human Interaction Database

    • Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3, organism-specific biosystem (from REACTOME)
      Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3, organism-specific biosystemPKN1, activated by phosphorylation at threonine T774, binds activated AR (androgen receptor) and promotes transcription from AR-regulated promoters. On one hand, phosphorylated PKN1 promotes the form...
    • Activation of HOX genes during differentiation, organism-specific biosystem (from REACTOME)
      Activation of HOX genes during differentiation, organism-specific biosystemHox genes encode proteins that contain the DNA-binding homeobox motif and control early patterning of segments in the embryo as well as later events in development (reviewed in Rezsohazy et al. 2015)...
    • Activation of anterior HOX genes in hindbrain development during early embryogenesis, organism-specific biosystem (from REACTOME)
      Activation of anterior HOX genes in hindbrain development during early embryogenesis, organism-specific biosystemIn mammals, anterior Hox genes may be defined as paralog groups 1 to 4 (Natale et al. 2011), which are involved in development of the hindbrain through sequential expression in the rhombomeres, trans...
    • Alcoholism, organism-specific biosystem (from KEGG)
      Alcoholism, organism-specific biosystemAlcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the reward...
    • Alcoholism, conserved biosystem (from KEGG)
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    • Amyloid fiber formation, organism-specific biosystem (from REACTOME)
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    • B-WICH complex positively regulates rRNA expression, organism-specific biosystem (from REACTOME)
      B-WICH complex positively regulates rRNA expression, organism-specific biosystemThe B-WICH complex is a large 3 Mdalton complex containing SMARCA5 (SNF2H), BAZ1B (WSTF), ERCC6 (CSB), MYO1C (Nuclear myosin 1c) (Cavellan et al. 2006, Percipalle et al. 2006, Vintermist et al. 2001,...
    • Cell Cycle, organism-specific biosystem (from REACTOME)
      Cell Cycle, organism-specific biosystem
      Cell Cycle
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    • Cellular Senescence, organism-specific biosystem (from REACTOME)
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    • Cellular responses to stress, organism-specific biosystem (from REACTOME)
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    • Chromatin modifying enzymes, organism-specific biosystem (from REACTOME)
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    • Chromosome Maintenance, organism-specific biosystem (from REACTOME)
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      DNA Damage/Telomere Stress Induced Senescence, organism-specific biosystemReactive oxygen species (ROS), whose concentration increases in senescent cells due to oncogenic RAS-induced mitochondrial dysfunction (Moiseeva et al. 2009) or due to environmental stress, cause DNA...
    • DNA Double Strand Break Response, organism-specific biosystem (from REACTOME)
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      DNA Double-Strand Break Repair, organism-specific biosystemNumerous types of DNA damage can occur within a cell due to the endogenous production of oxygen free radicals, normal alkylation reactions, or exposure to exogenous radiations and chemicals. Double-s...
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      DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
    • DNA damage response, organism-specific biosystem (from WikiPathways)
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    • DNA methylation, organism-specific biosystem (from REACTOME)
      DNA methylation, organism-specific biosystemMethylation of cytosine is catalyzed by a family of DNA methyltransferases (DNMTs): DNMT1, DNMT3A, and DNMT3B transfer methyl groups from S-adenosylmethionine to cytosine, producing 5-methylcytosine ...
    • Deposition of new CENPA-containing nucleosomes at the centromere, organism-specific biosystem (from REACTOME)
      Deposition of new CENPA-containing nucleosomes at the centromere, organism-specific biosystemEukaryotic centromeres are marked by a unique form of histone H3, designated CENPA in humans. In human cells newly synthesized CENPA is deposited in nucleosomes at the centromere during late telophas...
    • Developmental Biology, organism-specific biosystem (from REACTOME)
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    • ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression, organism-specific biosystem (from REACTOME)
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    • HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA), organism-specific biosystem (from REACTOME)
      HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA), organism-specific biosystemHomology directed repair (HDR) of replication-independent DNA double strand breaks (DSBs) via homologous recombination repair (HRR) or single strand annealing (SSA) requires the activation of ATM fol...
    • Homology Directed Repair, organism-specific biosystem (from REACTOME)
      Homology Directed Repair, organism-specific biosystemHomology directed repair (HDR) of DNA double strand breaks (DSBs) requires resection of DNA DSB ends. Resection creates 3'-ssDNA overhangs which then anneal with a homologous DNA sequence. This homol...
    • M Phase, organism-specific biosystem (from REACTOME)
      M Phase, organism-specific biosystemMitosis, or the M phase, involves nuclear division and cytokinesis, where two identical daughter cells are produced. Mitosis involves prophase, prometaphase, metaphase, anaphase, and telophase. Fin...
    • Meiosis, organism-specific biosystem (from REACTOME)
      Meiosis, organism-specific biosystemDuring meiosis the replicated chromosomes of a single diploid cell are segregated into 4 haploid daughter cells by two successive divisions, meiosis I and meiosis II. In meiosis I, the distinguishing...
    • Meiotic recombination, organism-specific biosystem (from REACTOME)
      Meiotic recombination, organism-specific biosystemMeiotic recombination exchanges segments of duplex DNA between chromosomal homologs, generating genetic diversity (reviewed in Handel and Schimenti 2010, Inagaki et al. 2010, Cohen et al. 2006). Ther...
    • Meiotic synapsis, organism-specific biosystem (from REACTOME)
      Meiotic synapsis, organism-specific biosystemMeiotic synapsis is the stable physical pairing of homologous chromosomes that begins in leptonema of prophase I and lasts until anaphase of prophase I. First, short segments of axial elements form a...
    • Metabolism of proteins, organism-specific biosystem (from REACTOME)
      Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
    • Mitotic Prophase, organism-specific biosystem (from REACTOME)
      Mitotic Prophase, organism-specific biosystemDuring prophase, the chromatin in the nucleus condenses, and the nucleolus disappears. Centrioles begin moving to the opposite poles or sides of the cell. Some of the fibers that extend from the cen...
    • Negative epigenetic regulation of rRNA expression, organism-specific biosystem (from REACTOME)
      Negative epigenetic regulation of rRNA expression, organism-specific biosystemTranscription of rRNA genes is controlled by epigenetic activation and repression (reviewed in McStay and Grummt 2008, Goodfellow and Zomerdijk 2012, Grummt and Langst 2013). About half of the roughl...
    • NoRC negatively regulates rRNA expression, organism-specific biosystem (from REACTOME)
      NoRC negatively regulates rRNA expression, organism-specific biosystemOnly about half of the rRNA gene copies in a cell are expressed. The remaining copies are silenced by modifications to histones and DNA (reviewed in Santoro and Grummt 2001, Grummt 2007, Preuss and P...
    • Nonhomologous End-Joining (NHEJ), organism-specific biosystem (from REACTOME)
      Nonhomologous End-Joining (NHEJ), organism-specific biosystemThe nonhomologous end joining (NHEJ) pathway is initiated in response to the formation of DNA double-strand breaks (DSBs) induced by DNA-damaging agents, such as ionizing radiation. DNA DSBs are reco...
    • Nucleosome assembly, organism-specific biosystem (from REACTOME)
      Nucleosome assembly, organism-specific biosystemThe formation of centromeric chromatin assembly outside the context of DNA replication involves the assembly of nucleosomes containing the histone H3 variant CenH3 (also called CENP-A).
    • Oxidative Stress Induced Senescence, organism-specific biosystem (from REACTOME)
      Oxidative Stress Induced Senescence, organism-specific biosystemOxidative stress, caused by increased concentration of reactive oxygen species (ROS) in the cell, can happen as a consequence of mitochondrial dysfunction induced by the oncogenic RAS (Moiseeva et al...
    • PRC2 methylates histones and DNA, organism-specific biosystem (from REACTOME)
      PRC2 methylates histones and DNA, organism-specific biosystemPolycomb group proteins are responsible for the heritable repression of genes during development (Lee et al. 2006, Ku et al. 2008, reviewed in Simon and Kingston 2009, Margueron and Reinberg 2011, Di...
    • Packaging Of Telomere Ends, organism-specific biosystem (from REACTOME)
      Packaging Of Telomere Ends, organism-specific biosystemMultiple steps, including C-strand resection, telomerase-mediated elongation, and C-strand synthesis are involved in processing and maintaining the telomere. Though this module posits a linear trans...
    • Positive epigenetic regulation of rRNA expression, organism-specific biosystem (from REACTOME)
      Positive epigenetic regulation of rRNA expression, organism-specific biosystemTranscription of rRNA genes is controlled by epigenetic activation and repression (reviewed in Percipalle and Farrants 2006, McStay and Grummt 2008, Goodfellow and Zomerdijk 2012, Grummt and Langst 2...
    • Processing of DNA double-strand break ends, organism-specific biosystem (from REACTOME)
      Processing of DNA double-strand break ends, organism-specific biosystemHomology directed repair (HDR) through homologous recombination (HRR) or single strand annealing (SSA) requires extensive resection of DNA double strand break (DSB) ends (Thompson and Limoli 2003, Ci...
    • Proteasome Degradation, organism-specific biosystem (from WikiPathways)
      Proteasome Degradation, organism-specific biosystem
      Proteasome Degradation
    • RHO GTPase Effectors, organism-specific biosystem (from REACTOME)
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    • RHO GTPases activate PKNs, organism-specific biosystem (from REACTOME)
      RHO GTPases activate PKNs, organism-specific biosystemProtein kinases N (PKN), also known as protein kinase C-related kinases (PKR) feature a C-terminal serine/threonine kinase domain and three RHO-binding motifs at the N-terminus. RHO GTPases RHOA, RHO...
    • RMTs methylate histone arginines, organism-specific biosystem (from REACTOME)
      RMTs methylate histone arginines, organism-specific biosystemArginine methylation is a common post-translational modification; around 2% of arginine residues are methylated in rat liver nuclei (Boffa et al. 1977). Arginine can be methylated in 3 different ways...
    • RNA Polymerase I Chain Elongation, organism-specific biosystem (from REACTOME)
      RNA Polymerase I Chain Elongation, organism-specific biosystem
      RNA Polymerase I Chain Elongation
    • RNA Polymerase I Promoter Clearance, organism-specific biosystem (from REACTOME)
      RNA Polymerase I Promoter Clearance, organism-specific biosystemPromoter clearance is one of the rate-limiting steps in Polymerase I transcription. This step is composed of three phases, promoter opening, transcription initiation and promoter escape.
    • RNA Polymerase I Promoter Opening, organism-specific biosystem (from REACTOME)
      RNA Polymerase I Promoter Opening, organism-specific biosystemThe activity of the upstream binding factor (UBF-1) plays an important role in the regulation of rRNA synthesis. Studies reveal that phosphorylation of UBF-1 is required for its interaction with the ...
    • RNA Polymerase I Transcription, organism-specific biosystem (from REACTOME)
      RNA Polymerase I Transcription, organism-specific biosystemThe rRNA genes are transcribed by RNA polymerase I, one of three eukaryotic nuclear RNA polymerases. The polymerase is a multisubunit complex, composed of two large subunits (the most conserved porti...
    • RNA Polymerase I, RNA Polymerase III, and Mitochondrial Transcription, organism-specific biosystem (from REACTOME)
      RNA Polymerase I, RNA Polymerase III, and Mitochondrial Transcription, organism-specific biosystemTranscription by RNA Polymerase I, RNA Polymerase III and transcription from mitochondrial promoters.
    • Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks, organism-specific biosystem (from REACTOME)
      Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks, organism-specific biosystemActivated ATM phosphorylates a number of proteins involved in the DNA damage checkpoint and DNA repair (Thompson and Schild 2002, Ciccia and Elledge 2010), thereby triggering and coordinating accumul...
    • SIRT1 negatively regulates rRNA Expression, organism-specific biosystem (from REACTOME)
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    • Senescence-Associated Secretory Phenotype (SASP), organism-specific biosystem (from REACTOME)
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    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by Rho GTPases, organism-specific biosystem (from REACTOME)
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    • Signaling by Wnt, organism-specific biosystem (from REACTOME)
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    • Systemic lupus erythematosus, organism-specific biosystem (from KEGG)
      Systemic lupus erythematosus, organism-specific biosystemSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and cert...
    • Systemic lupus erythematosus, conserved biosystem (from KEGG)
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    • TCF dependent signaling in response to WNT, organism-specific biosystem (from REACTOME)
      TCF dependent signaling in response to WNT, organism-specific biosystem19 WNT ligands and 10 FZD receptors have been identified in human cells; interactions amongst these ligands and receptors vary in a developmental and tissue-specific manner and lead to activation of ...
    • Telomere Maintenance, organism-specific biosystem (from REACTOME)
      Telomere Maintenance, organism-specific biosystemTelomeres are protein-DNA complexes at the ends of linear chromosomes that are important for genome stability. Telomeric DNA in humans, as in many eukaryotic organisms, consists of tandem repeats (B...
    • Transcriptional regulation by small RNAs, organism-specific biosystem (from REACTOME)
      Transcriptional regulation by small RNAs, organism-specific biosystemRecent evidence indicates that small RNAs participate in transcriptional regulation in addition to post-transcriptional silencing. Components of the RNAi machinery (ARGONAUTE1 (AGO1, EIF2C1), AGO2 (E...
    • miRNAs involved in DDR, organism-specific biosystem (from WikiPathways)
      miRNAs involved in DDR, organism-specific biosystemMicroRNA clusters involved in de DNA damage response. Genes they regulated and genes that regulate them. All genes presented in this pathway can also be found in the pathway "DNA damage response(Homo...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    DNA binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    damaged DNA binding IEA
    Inferred from Electronic Annotation
    more info
     
    enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    histone binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein heterodimerization activity IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    DNA damage checkpoint IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular response to DNA damage stimulus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular response to gamma radiation IEA
    Inferred from Electronic Annotation
    more info
     
    cellular senescence IEA
    Inferred from Electronic Annotation
    more info
     
    cerebral cortex development IEA
    Inferred from Electronic Annotation
    more info
     
    chromatin silencing IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    double-strand break repair NAS
    Non-traceable Author Statement
    more info
    PubMed 
    double-strand break repair via homologous recombination IEA
    Inferred from Electronic Annotation
    more info
     
    double-strand break repair via nonhomologous end joining TAS
    Traceable Author Statement
    more info
     
    meiotic cell cycle IEA
    Inferred from Electronic Annotation
    more info
     
    nucleosome assembly NAS
    Non-traceable Author Statement
    more info
    PubMed 
    positive regulation of DNA repair NAS
    Non-traceable Author Statement
    more info
    PubMed 
    response to ionizing radiation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    spermatogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    viral process IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    XY body IEA
    Inferred from Electronic Annotation
    more info
     
    colocalizes_with chromosome, telomeric region IDA
    Inferred from Direct Assay
    more info
    PubMed 
    condensed nuclear chromosome IEA
    Inferred from Electronic Annotation
    more info
     
    extracellular exosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    male germ cell nucleus IEA
    Inferred from Electronic Annotation
    more info
     
    nuclear chromatin IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    nucleosome IEA
    Inferred from Electronic Annotation
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    replication fork IEA
    Inferred from Electronic Annotation
    more info
     
    site of double-strand break IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    histone H2AX
    Names
    H2A histone family, member X
    H2AX histone
    histone H2A.x

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_002105.2NP_002096.1  histone H2AX

      See identical proteins and their annotated locations for NP_002096.1

      Status: REVIEWED

      Source sequence(s)
      BC004915, BC011694, BC013416, X14850
      Consensus CDS
      CCDS8410.1
      UniProtKB/Swiss-Prot
      P16104
      Related
      ENSP00000434024, OTTHUMP00000232149, ENST00000530167, OTTHUMT00000388330
      Conserved Domains (2) summary
      PTZ00017
      Location:1131
      PTZ00017; histone H2A; Provisional
      cd00074
      Location:6120
      H2A; Histone 2A; H2A is a subunit of the nucleosome. The nucleosome is an octamer containing two H2A, H2B, H3, and H4 subunits. The H2A subunit performs essential roles in maintaining structural integrity of the nucleosome, chromatin condensation, and binding ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p7 Primary Assembly

      Range
      119093874..119095467 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018922.2 Alternate CHM1_1.1

      Range
      118850886..118852479 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)