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 ... See more...

Aliases for H2AX Gene

Aliases for H2AX Gene

  • H2A.X Variant Histone 2 3
  • H2A Histone Family Member X 2 3 5
  • Histone H2A.X 3 4
  • Histone H2AX 3 4
  • H2AFX 3 5
  • H2A Histone Family, Member X 2
  • H2AX Histone 3
  • H2A.X 3
  • H2A/X 3
  • H2a/X 4

External Ids for H2AX Gene

Previous HGNC Symbols for H2AX Gene

  • H2AFX

Summaries for H2AX Gene

Entrez Gene Summary for H2AX Gene

  • 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]

GeneCards Summary for H2AX Gene

H2AX (H2A.X Variant Histone) is a Protein Coding gene. Diseases associated with H2AX include Nijmegen Breakage Syndrome and Ataxia-Telangiectasia. Among its related pathways are Signaling by Wnt and Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3. An important paralog of this gene is H2AC21.

UniProtKB/Swiss-Prot Summary for H2AX Gene

  • 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.

Gene Wiki entry for H2AX Gene

Additional gene information for H2AX Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for H2AX Gene

Genomics for H2AX Gene

GeneHancer (GH) Regulatory Elements for H2AX Gene

Promoters and enhancers for H2AX Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around H2AX on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for H2AX

Genomic Locations for H2AX Gene

Genomic Locations for H2AX Gene
chr11:119,093,854-119,095,467
(GRCh38/hg38)
Size:
1,614 bases
Orientation:
Minus strand
chr11:118,964,564-118,966,177
(GRCh37/hg19)
Size:
1,614 bases
Orientation:
Minus strand

Genomic View for H2AX Gene

Genes around H2AX on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
H2AX Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for H2AX Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for H2AX Gene

Proteins for H2AX Gene

  • Protein details for H2AX Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P16104-H2AX_HUMAN
    Recommended name:
    Histone H2AX
    Protein Accession:
    P16104
    Secondary Accessions:
    • Q4ZGJ7
    • Q6IAS5

    Protein attributes for H2AX Gene

    Size:
    143 amino acids
    Molecular mass:
    15145 Da
    Quaternary structure:
    • 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 (Probable). Interacts with numerous proteins required for DNA damage signaling and repair when phosphorylated on Ser-140 (PubMed:12419185, PubMed:12607005, PubMed:15201865). These include MDC1, TP53BP1, BRCA1 and the MRN complex, composed of MRE11, RAD50, and NBN (PubMed:12419185, PubMed:12607005, PubMed:15201865). Interaction with the MRN complex is mediated at least in part by NBN (PubMed:12419185). Also interacts with DHX9/NDHII when phosphorylated on Ser-140 and MCPH1 when phosphorylated at Ser-140 or Tyr-143 (PubMed:15613478). Interacts with ARRB2; the interaction is detected in the nucleus upon OR1D2 stimulation (PubMed:16820410). Interacts with WRAP53/TCAB1 (PubMed:26734725, PubMed:27715493).
    • (Microbial infection) Interacts with Epstein-Barr virus protein EBNA6.

    Three dimensional structures from OCA and Proteopedia for H2AX Gene

neXtProt entry for H2AX Gene

Post-translational modifications for H2AX Gene

  • 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).
  • 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.
  • 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).
  • Ubiquitination at Lys14, Lys16, Lys120, Lys128, and Lys135
  • Modification sites at PhosphoSitePlus

Other Protein References for H2AX Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for H2AX Gene

Domains & Families for H2AX Gene

Gene Families for H2AX Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for H2AX Gene

Suggested Antigen Peptide Sequences for H2AX Gene

GenScript: Design optimal peptide antigens:
  • H2A.X protein (A0N6L7_HUMAN)
  • Histone H2A.x (H2AX_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P16104

UniProtKB/Swiss-Prot:

H2AX_HUMAN :
  • The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family.
  • Belongs to the histone H2A family.
Domain:
  • The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family.
Family:
  • Belongs to the histone H2A family.
genes like me logo Genes that share domains with H2AX: view

Function for H2AX Gene

Molecular function for H2AX Gene

UniProtKB/Swiss-Prot Function:
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.

Phenotypes From GWAS Catalog for H2AX Gene

Gene Ontology (GO) - Molecular Function for H2AX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003677 DNA binding NAS,IBA 2587254
GO:0003684 damaged DNA binding IEA --
GO:0005515 protein binding IPI 12419185
GO:0019899 enzyme binding IPI 19234442
GO:0042393 histone binding IPI 19234442
genes like me logo Genes that share ontologies with H2AX: view
genes like me logo Genes that share phenotypes with H2AX: view

Animal Models for H2AX Gene

MGI Knock Outs for H2AX:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for H2AX

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for H2AX Gene

Localization for H2AX Gene

Subcellular locations from UniProtKB/Swiss-Prot for H2AX Gene

Nucleus. Chromosome.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for H2AX gene
Compartment Confidence
cytoskeleton 5
nucleus 5
mitochondrion 3
plasma membrane 2
extracellular 2
endoplasmic reticulum 2
cytosol 2
lysosome 2
peroxisome 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear speckles (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for H2AX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000781 colocalizes_with chromosome, telomeric region IDA 15149599
GO:0000785 chromatin IEA --
GO:0000786 nucleosome IEA --
GO:0000790 nuclear chromatin IBA 21873635
GO:0000794 condensed nuclear chromosome IEA --
genes like me logo Genes that share ontologies with H2AX: view

Pathways & Interactions for H2AX Gene

PathCards logo

SuperPathways for H2AX Gene

SuperPathway Contained pathways
1 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
2 DNA Double-Strand Break Repair
3 Cellular Senescence (REACTOME)
4 Chromosome Maintenance
5 Cell Cycle, Mitotic
.60
genes like me logo Genes that share pathways with H2AX: view

Pathways by source for H2AX Gene

2 GeneGo (Thomson Reuters) pathways for H2AX Gene
  • DNA damage_Role of Brca1 and Brca2 in DNA repair
  • Signal transduction Activin A signaling regulation
1 Qiagen pathway for H2AX Gene
  • ATM Pathway
2 Cell Signaling Technology pathways for H2AX Gene
1 GeneTex pathway for H2AX Gene

SIGNOR curated interactions for H2AX Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for H2AX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000077 DNA damage checkpoint IDA 17974976
GO:0000724 double-strand break repair via homologous recombination IEA --
GO:0006281 DNA repair IEA --
GO:0006302 double-strand break repair NAS 19234442
GO:0006303 double-strand break repair via nonhomologous end joining TAS --
genes like me logo Genes that share ontologies with H2AX: view

Drugs & Compounds for H2AX Gene

(23) Drugs for H2AX Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(13) Additional Compounds for H2AX Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with H2AX: view

Transcripts for H2AX Gene

mRNA/cDNA for H2AX Gene

1 REFSEQ mRNAs :
5 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for H2AX

Alternative Splicing Database (ASD) splice patterns (SP) for H2AX Gene

No ASD Table

Relevant External Links for H2AX Gene

GeneLoc Exon Structure for
H2AX

Expression for H2AX Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for H2AX

SOURCE GeneReport for Unigene cluster for H2AX Gene:

Hs.477879

Evidence on tissue expression from TISSUES for H2AX Gene

  • Lung(4.8)
  • Nervous system(3.8)
  • Intestine(3.5)
  • Skin(3)
  • Eye(2.7)
  • Blood(2.6)
  • Pancreas(2.6)
  • Bone marrow(2.1)
  • Liver(2.1)
No Expression Related Data Available

No data available for mRNA expression in normal human tissues , mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for H2AX Gene

Orthologs for H2AX Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for H2AX Gene

Organism Taxonomy Gene Similarity Type Details
dog
(Canis familiaris)
Mammalia H2AFX 31
  • 99 (a)
OneToOne
LOC489372 30
  • 95.57 (n)
cow
(Bos Taurus)
Mammalia H2AFX 31 30
  • 94.41 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia H2AFX 31
  • 94 (a)
OneToOne
mouse
(Mus musculus)
Mammalia H2afx 31 30
  • 92.54 (n)
OneToOne
H2ax 17
rat
(Rattus norvegicus)
Mammalia H2afx 30
  • 92.07 (n)
chimpanzee
(Pan troglodytes)
Mammalia H2AFX 31
  • 92 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia H2AFX 31
  • 88 (a)
OneToOne
chicken
(Gallus gallus)
Aves H2AFX 31 30
  • 79.25 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 81 (a)
OneToMany
-- 31
  • 80 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100487455 30
  • 74.1 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.18740 30
zebrafish
(Danio rerio)
Actinopterygii h2afx 31 30
  • 75.82 (n)
ManyToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons HTA12 30
  • 56.79 (n)
rice
(Oryza sativa)
Liliopsida Os03g0279200 30
  • 75.26 (n)
corn
(Zea mays)
Liliopsida Zm.16259 30
barley
(Hordeum vulgare)
Liliopsida Hv.836 30
Species where no ortholog for H2AX was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for H2AX Gene

ENSEMBL:
Gene Tree for H2AX (if available)
TreeFam:
Gene Tree for H2AX (if available)
Aminode:
Evolutionary constrained regions (ECRs) for H2AX: view image

Paralogs for H2AX Gene

Variants for H2AX Gene

Additional dbSNP identifiers (rs#s) for H2AX Gene

Structural Variations from Database of Genomic Variants (DGV) for H2AX Gene

Variant ID Type Subtype PubMed ID
nsv826102 CNV gain 20364138

Variation tolerance for H2AX Gene

Residual Variation Intolerance Score: 36.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.07; 1.58% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for H2AX Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
H2AX

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for H2AX Gene

Disorders for H2AX Gene

MalaCards: The human disease database

(25) MalaCards diseases for H2AX Gene - From: DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search H2AX in MalaCards View complete list of genes associated with diseases

Additional Disease Information for H2AX

genes like me logo Genes that share disorders with H2AX: view

No data available for UniProtKB/Swiss-Prot and Genatlas for H2AX Gene

Publications for H2AX Gene

  1. Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions. (PMID: 19234442) Cook PJ … Rosenfeld MG (Nature 2009) 3 4 23 54
  2. Doxorubicin activates ATM-dependent phosphorylation of multiple downstream targets in part through the generation of reactive oxygen species. (PMID: 15489221) Kurz EU … Lees-Miller SP (The Journal of biological chemistry 2004) 3 4 23 54
  3. ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. (PMID: 15059890) Stiff T … Jeggo PA (Cancer research 2004) 3 4 23 54
  4. Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX. (PMID: 12697768) Ward IM … Chen J (The Journal of biological chemistry 2003) 3 4 23 54
  5. MDC1 is a mediator of the mammalian DNA damage checkpoint. (PMID: 12607005) Stewart GS … Elledge SJ (Nature 2003) 3 4 23 54

Products for H2AX Gene