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P16104

- H2AX_HUMAN

UniProt

P16104 - H2AX_HUMAN

Protein

Histone H2AX

Gene

H2AFX

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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.4 Publications

    GO - Molecular functioni

    1. damaged DNA binding Source: Ensembl
    2. DNA binding Source: UniProtKB
    3. enzyme binding Source: UniProtKB
    4. histone binding Source: UniProtKB
    5. protein binding Source: UniProtKB

    GO - Biological processi

    1. cellular response to DNA damage stimulus Source: BHF-UCL
    2. DNA damage checkpoint Source: UniProtKB
    3. DNA repair Source: Reactome
    4. double-strand break repair Source: UniProtKB
    5. double-strand break repair via homologous recombination Source: Reactome
    6. meiotic nuclear division Source: UniProtKB-KW
    7. nucleosome assembly Source: UniProtKB
    8. positive regulation of DNA repair Source: UniProtKB
    9. response to ionizing radiation Source: UniProtKB
    10. spermatogenesis Source: Ensembl

    Keywords - Biological processi

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

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169185. DNA Damage/Telomere Stress Induced Senescence.
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_172744. Condensation of Prophase Chromosomes.
    REACT_1884. MRN complex relocalizes to nuclear foci.
    REACT_1924. ATM mediated phosphorylation of repair proteins.
    REACT_200753. formation of the beta-catenin:TCF transactivating complex.
    REACT_200808. PRC2 methylates histones and DNA.
    REACT_200827. SIRT1 negatively regulates rRNA Expression.
    REACT_200856. NoRC negatively regulates rRNA expression.
    REACT_2204. RNA Polymerase I Chain Elongation.
    REACT_22186. Deposition of new CENPA-containing nucleosomes at the centromere.
    REACT_2232. RNA Polymerase I Promoter Opening.
    REACT_27271. Meiotic recombination.
    REACT_486. Assembly of the RAD50-MRE11-NBS1 complex at DNA double-strand breaks.
    REACT_75792. Meiotic synapsis.
    REACT_75925. Amyloids.
    REACT_7963. Packaging Of Telomere Ends.
    REACT_97. Recruitment of repair and signaling proteins to double-strand breaks.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Histone H2AX
    Short name:
    H2a/x
    Alternative name(s):
    Histone H2A.X
    Gene namesi
    Name:H2AFX
    Synonyms:H2AX
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:4739. H2AFX.

    Subcellular locationi

    GO - Cellular componenti

    1. condensed nuclear chromosome Source: Ensembl
    2. male germ cell nucleus Source: Ensembl
    3. nuclear chromatin Source: Ensembl
    4. nucleoplasm Source: Reactome
    5. nucleosome Source: UniProtKB-KW
    6. nucleus Source: UniProtKB
    7. replication fork Source: Ensembl
    8. site of double-strand break Source: MGI
    9. XY body Source: Ensembl

    Keywords - Cellular componenti

    Chromosome, Nucleosome core, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi141 – 1411Q → N: Reduced phosphorylation of S-140 in response to DNA damage. 1 Publication
    Mutagenesisi143 – 1431Y → F: Displays a reduced apoptotic response. S-140 phosphorylation is reduced. 2 Publications

    Organism-specific databases

    PharmGKBiPA29116.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 143142Histone H2AXPRO_0000055242Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserineBy similarity
    Modified residuei2 – 21PhosphoserineBy similarity
    Modified residuei6 – 61N6-acetyllysineBy similarity
    Modified residuei10 – 101N6-acetyllysineBy similarity
    Cross-linki14 – 14Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki16 – 16Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Modified residuei37 – 371N6-acetyllysineBy similarity
    Cross-linki120 – 120Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Modified residuei140 – 1401Phosphoserine; by ATM, ATR and PRKDC16 Publications
    Modified residuei143 – 1431Phosphotyrosine; by WSTF2 Publications

    Post-translational modificationi

    Phosphorylated on Ser-140 (to form gamma-H2AX or H2AX139ph) 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. Phosphorylation of Ser-140 (H2AX139ph) in response to ionizing radiation is mediated by both ATM and PRKDC while defects in DNA replication induce Ser-140 phosphorylation (H2AX139ph) subsequent to activation of ATR and PRKDC. Dephosphorylation of Ser-140 by PP2A is required for DNA DSB repair. In meiosis, Ser-140 phosphorylation (H2AX139ph) may occur at synaptonemal complexes during leptotene as an ATM-dependent response to the formation of programmed DSBs by SPO11. Ser-140 phosphorylation (H2AX139ph) may subsequently occurs at unsynapsed regions of both autosomes and the XY bivalent during zygotene, downstream of ATR and BRCA1 activation. Ser-140 phosphorylation (H2AX139ph) may also be required for transcriptional repression of unsynapsed chromatin and meiotic sex chromosome inactivation (MSCI), whereby the X and Y chromosomes condense in pachytene to form the heterochromatic XY-body. During immunoglobulin class switch recombination in lymphocytes, Ser-140 phosphorylation (H2AX139ph) may occur at sites of DNA-recombination subsequent to activation of the activation-induced cytidine deaminase AICDA. Phosphorylation at Tyr-143 (H2AXY142ph) by BAZ1B/WSTF determines the relative recruitment of either DNA repair or pro-apoptotic factors. Phosphorylation at Tyr-143 (H2AXY142ph) favors the recruitment of APBB1/FE65 and pro-apoptosis factors such as MAPK8/JNK1, triggering apoptosis. In contrast, dephosphorylation of Tyr-143 by EYA proteins (EYA1, EYA2, EYA3 or EYA4) favors the recruitment of MDC1-containing DNA repair complexes to the tail of phosphorylated Ser-140 (H2AX139ph).18 Publications
    Monoubiquitination of Lys-120 (H2AXK119ub) by RING1 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression By similarity. 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 similarity5 Publications
    Acetylation at Lys-37 increases in S and G2 phases. This modification has been proposed to play a role in DNA double-strand break repair By similarity.By similarity

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP16104.
    PaxDbiP16104.
    PRIDEiP16104.

    PTM databases

    PhosphoSiteiP16104.

    Expressioni

    Developmental stagei

    Synthesized in G1 as well as in S-phase.

    Gene expression databases

    BgeeiP16104.
    CleanExiHS_H2AFX.
    GenevestigatoriP16104.

    Organism-specific databases

    HPAiCAB012264.

    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-140. These include MDC1, TP53BP1, BRCA1 and the MRN complex, composed of MRE11A, RAD50, and NBN. Interaction with the MRN complex is mediated at least in part by NBN. Also interacts with DHX9/NDHII when phosphorylated on Ser-140 and MCPH1 when phosphorylated at Ser-140 or Tyr-143. Interacts with ARRB2; the interaction is detected in the nucleus upon OR1D2 stimulation.5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Aifm1Q9Z0X12EBI-494830,EBI-5326677From a different organism.
    BRCA1P383984EBI-494830,EBI-349905
    HIST3H3Q1669511EBI-494830,EBI-358900
    MDC1Q146767EBI-494830,EBI-495644
    MRE11AP499594EBI-494830,EBI-396513
    NBNO6093412EBI-494830,EBI-494844
    PAXIP1Q6ZW49-17EBI-494830,EBI-7521368
    PPM1DO152976EBI-494830,EBI-1551512
    SMARCA4P515329EBI-494830,EBI-302489

    Protein-protein interaction databases

    BioGridi109268. 206 interactions.
    DIPiDIP-33604N.
    IntActiP16104. 160 interactions.
    MINTiMINT-1338182.
    STRINGi9606.ENSP00000364310.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1YDPX-ray1.90P78-86[»]
    2AZMX-ray2.41C/D134-143[»]
    2D31X-ray3.20C/F78-86[»]
    2DYPX-ray2.50C78-86[»]
    3SHVX-ray2.10C/D134-143[»]
    3SQDX-ray2.15C/D134-143[»]
    3SZMX-ray2.63I/J/K/L/M/N/O/P134-143[»]
    3U3ZX-ray1.50B140-143[»]
    ProteinModelPortaliP16104.
    SMRiP16104. Positions 14-119.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP16104.

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi140 – 1412[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

    eggNOGiCOG5262.
    HOGENOMiHOG000234652.
    HOVERGENiHBG009342.
    InParanoidiP16104.
    KOiK11251.
    OMAiSKGECIN.
    OrthoDBiEOG7M0NTR.
    PhylomeDBiP16104.
    TreeFamiTF300137.

    Family and domain databases

    Gene3Di1.10.20.10. 1 hit.
    InterProiIPR009072. Histone-fold.
    IPR007125. Histone_core_D.
    IPR002119. Histone_H2A.
    [Graphical view]
    PfamiPF00125. Histone. 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.

    P16104-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSGRGKTGGK ARAKAKSRSS RAGLQFPVGR VHRLLRKGHY AERVGAGAPV    50
    YLAAVLEYLT AEILELAGNA ARDNKKTRII PRHLQLAIRN DEELNKLLGG 100
    VTIAQGGVLP NIQAVLLPKK TSATVGPKAP SGGKKATQAS QEY 143
    Length:143
    Mass (Da):15,145
    Last modified:January 23, 2007 - v2
    Checksum:iD4683775C2E6C3A9
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti78 – 781R → L in CAG33360. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X14850 mRNA. Translation: CAA32968.1.
    CR457079 mRNA. Translation: CAG33360.1.
    DQ015918 Genomic DNA. Translation: AAY22178.1.
    BC004915 mRNA. Translation: AAH04915.1.
    BC011694 mRNA. Translation: AAH11694.1.
    BC013416 mRNA. Translation: AAH13416.1.
    CCDSiCCDS8410.1.
    PIRiS07631.
    RefSeqiNP_002096.1. NM_002105.2.
    UniGeneiHs.477879.

    Genome annotation databases

    EnsembliENST00000375167; ENSP00000364310; ENSG00000188486.
    ENST00000530167; ENSP00000434024; ENSG00000188486.
    GeneIDi3014.
    KEGGihsa:3014.
    UCSCiuc001pvg.3. human.

    Polymorphism databases

    DMDMi121992.

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs
    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X14850 mRNA. Translation: CAA32968.1 .
    CR457079 mRNA. Translation: CAG33360.1 .
    DQ015918 Genomic DNA. Translation: AAY22178.1 .
    BC004915 mRNA. Translation: AAH04915.1 .
    BC011694 mRNA. Translation: AAH11694.1 .
    BC013416 mRNA. Translation: AAH13416.1 .
    CCDSi CCDS8410.1.
    PIRi S07631.
    RefSeqi NP_002096.1. NM_002105.2.
    UniGenei Hs.477879.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1YDP X-ray 1.90 P 78-86 [» ]
    2AZM X-ray 2.41 C/D 134-143 [» ]
    2D31 X-ray 3.20 C/F 78-86 [» ]
    2DYP X-ray 2.50 C 78-86 [» ]
    3SHV X-ray 2.10 C/D 134-143 [» ]
    3SQD X-ray 2.15 C/D 134-143 [» ]
    3SZM X-ray 2.63 I/J/K/L/M/N/O/P 134-143 [» ]
    3U3Z X-ray 1.50 B 140-143 [» ]
    ProteinModelPortali P16104.
    SMRi P16104. Positions 14-119.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109268. 206 interactions.
    DIPi DIP-33604N.
    IntActi P16104. 160 interactions.
    MINTi MINT-1338182.
    STRINGi 9606.ENSP00000364310.

    PTM databases

    PhosphoSitei P16104.

    Polymorphism databases

    DMDMi 121992.

    Proteomic databases

    MaxQBi P16104.
    PaxDbi P16104.
    PRIDEi P16104.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000375167 ; ENSP00000364310 ; ENSG00000188486 .
    ENST00000530167 ; ENSP00000434024 ; ENSG00000188486 .
    GeneIDi 3014.
    KEGGi hsa:3014.
    UCSCi uc001pvg.3. human.

    Organism-specific databases

    CTDi 3014.
    GeneCardsi GC11M118998.
    HGNCi HGNC:4739. H2AFX.
    HPAi CAB012264.
    MIMi 601772. gene.
    neXtProti NX_P16104.
    PharmGKBi PA29116.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5262.
    HOGENOMi HOG000234652.
    HOVERGENi HBG009342.
    InParanoidi P16104.
    KOi K11251.
    OMAi SKGECIN.
    OrthoDBi EOG7M0NTR.
    PhylomeDBi P16104.
    TreeFami TF300137.

    Enzyme and pathway databases

    Reactomei REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169185. DNA Damage/Telomere Stress Induced Senescence.
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_172744. Condensation of Prophase Chromosomes.
    REACT_1884. MRN complex relocalizes to nuclear foci.
    REACT_1924. ATM mediated phosphorylation of repair proteins.
    REACT_200753. formation of the beta-catenin:TCF transactivating complex.
    REACT_200808. PRC2 methylates histones and DNA.
    REACT_200827. SIRT1 negatively regulates rRNA Expression.
    REACT_200856. NoRC negatively regulates rRNA expression.
    REACT_2204. RNA Polymerase I Chain Elongation.
    REACT_22186. Deposition of new CENPA-containing nucleosomes at the centromere.
    REACT_2232. RNA Polymerase I Promoter Opening.
    REACT_27271. Meiotic recombination.
    REACT_486. Assembly of the RAD50-MRE11-NBS1 complex at DNA double-strand breaks.
    REACT_75792. Meiotic synapsis.
    REACT_75925. Amyloids.
    REACT_7963. Packaging Of Telomere Ends.
    REACT_97. Recruitment of repair and signaling proteins to double-strand breaks.

    Miscellaneous databases

    ChiTaRSi H2AFX. human.
    EvolutionaryTracei P16104.
    GeneWikii H2AFX.
    GenomeRNAii 3014.
    NextBioi 11948.
    PROi P16104.
    SOURCEi Search...

    Gene expression databases

    Bgeei P16104.
    CleanExi HS_H2AFX.
    Genevestigatori P16104.

    Family and domain databases

    Gene3Di 1.10.20.10. 1 hit.
    InterProi IPR009072. Histone-fold.
    IPR007125. Histone_core_D.
    IPR002119. Histone_H2A.
    [Graphical view ]
    Pfami PF00125. Histone. 1 hit.
    [Graphical view ]
    PRINTSi PR00620. HISTONEH2A.
    SMARTi SM00414. H2A. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47113. SSF47113. 1 hit.
    PROSITEi PS00046. HISTONE_H2A. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "H2A.X. a histone isoprotein with a conserved C-terminal sequence, is encoded by a novel mRNA with both DNA replication type and polyA 3' processing signals."
      Mannironi C., Bonner W.M., Hatch C.L.
      Nucleic Acids Res. 17:9113-9126(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
      Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    3. NIEHS SNPs program
      Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Lung and Placenta.
    5. "DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139."
      Rogakou E.P., Pilch D.R., Orr A.H., Ivanova V.S., Bonner W.M.
      J. Biol. Chem. 273:5858-5868(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-140, MUTAGENESIS OF GLN-141.
    6. "Megabase chromatin domains involved in DNA double-strand breaks in vivo."
      Rogakou E.P., Boon C., Redon C., Bonner W.M.
      J. Cell Biol. 146:905-916(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-140.
    7. "A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage."
      Paull T.T., Rogakou E.P., Yamazaki V., Kirchgessner C.U., Gellert M., Bonner W.M.
      Curr. Biol. 10:886-895(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-140.
    8. "Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139."
      Rogakou E.P., Nieves-Neira W., Boon C., Pommier Y., Bonner W.M.
      J. Biol. Chem. 275:9390-9395(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-140.
    9. "Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress."
      Ward I.M., Chen J.
      J. Biol. Chem. 276:47759-47762(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-140.
    10. "NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain."
      Kobayashi J., Tauchi H., Sakamoto S., Nakamura A., Morishima K., Matsuura S., Kobayashi T., Tamai K., Tanimoto K., Komatsu K.
      Curr. Biol. 12:1846-1851(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH NBN AND BRCA1, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-140.
    11. "Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX."
      Ward I.M., Minn K., Jorda K.G., Chen J.
      J. Biol. Chem. 278:19579-19582(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-140.
    12. "Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes."
      Furuta T., Takemura H., Liao Z.-Y., Aune G.J., Redon C., Sedelnikova O.A., Pilch D.R., Rogakou E.P., Celeste A., Chen H.T., Nussenzweig A., Aladjem M.I., Bonner W.M., Pommier Y.
      J. Biol. Chem. 278:20303-20312(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-140.
    13. "MDC1 is a mediator of the mammalian DNA damage checkpoint."
      Stewart G.S., Wang B., Bignell C.R., Taylor A.M.R., Elledge S.J.
      Nature 421:961-966(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH MDC1 AND TP53BP1, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-140.
    14. "DNA-PK is activated by nucleosomes and phosphorylates H2AX within the nucleosomes in an acetylation-dependent manner."
      Park E.-J., Chan D.W., Park J.-H., Oettinger M.A., Kwon J.
      Nucleic Acids Res. 31:6819-6827(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-140.
    15. "ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation."
      Stiff T., O'Driscoll M., Rief N., Iwabuchi K., Loebrich M., Jeggo P.A.
      Cancer Res. 64:2390-2396(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-140.
    16. "Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-dependent chromatin retention."
      Lukas C., Melander F., Stucki M., Falck J., Bekker-Jensen S., Goldberg M., Lerenthal Y., Jackson S.P., Bartek J., Lukas J.
      EMBO J. 23:2674-2683(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH MDC1 AND NBN, SUBCELLULAR LOCATION.
    17. "Doxorubicin activates ATM-dependent phosphorylation of multiple downstream targets in part through the generation of reactive oxygen species."
      Kurz E.U., Douglas P., Lees-Miller S.P.
      J. Biol. Chem. 279:53272-53281(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-140.
    18. "Actinomycin D induces histone gamma-H2AX foci and complex formation of gamma-H2AX with Ku70 and nuclear DNA helicase II."
      Mischo H.E., Hemmerich P., Grosse F., Zhang S.
      J. Biol. Chem. 280:9586-9594(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DHX9, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-140.
    19. "gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair."
      Chowdhury D., Keogh M.-C., Ishii H., Peterson C.L., Buratowski S., Lieberman J.
      Mol. Cell 20:801-809(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: DEPHOSPHORYLATION.
    20. "Novel function of beta-arrestin2 in the nucleus of mature spermatozoa."
      Neuhaus E.M., Mashukova A., Barbour J., Wolters D., Hatt H.
      J. Cell Sci. 119:3047-3056(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ARRB2.
    21. "RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins."
      Mailand N., Bekker-Jensen S., Faustrup H., Melander F., Bartek J., Lukas C., Lukas J.
      Cell 131:887-900(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION.
    22. "RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly."
      Huen M.S.Y., Grant R., Manke I., Minn K., Yu X., Yaffe M.B., Chen J.
      Cell 131:901-914(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION.
    23. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic kidney.
    24. Cited for: UBIQUITINATION.
    25. "RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins."
      Doil C., Mailand N., Bekker-Jensen S., Menard P., Larsen D.H., Pepperkok R., Ellenberg J., Panier S., Durocher D., Bartek J., Lukas J., Lukas C.
      Cell 136:435-446(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION.
    26. Cited for: PHOSPHORYLATION AT TYR-143, MUTAGENESIS OF TYR-143.
    27. "Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions."
      Cook P.J., Ju B.G., Telese F., Wang X., Glass C.K., Rosenfeld M.G.
      Nature 458:591-596(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-143, MUTAGENESIS OF TYR-143.
    28. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    29. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    30. "RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA Damage signaling."
      Mattiroli F., Vissers J.H., van Dijk W.J., Ikpa P., Citterio E., Vermeulen W., Marteijn J.A., Sixma T.K.
      Cell 150:1182-1195(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION AT LYS-14 AND LYS-16 BY RNF168.
    31. "Specific recognition of phosphorylated tail of H2AX by the tandem BRCT domains of MCPH1 revealed by complex structure."
      Shao Z., Li F., Sy S.M., Yan W., Zhang Z., Gong D., Wen B., Huen M.S., Gong Q., Wu J., Shi Y.
      J. Struct. Biol. 177:459-468(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 134-143, PHOSPHORYLATION AT SER-140.

    Entry informationi

    Entry nameiH2AX_HUMAN
    AccessioniPrimary (citable) accession number: P16104
    Secondary accession number(s): Q4ZGJ7, Q6IAS5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 154 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3