H2ax
entrez
15270
canonical
uniprot
P27661
canonical
ensembl
ENSMUSG00000049932
resolver
ensp
ENSMUSP00000051432
resolver
enst
ENSMUST00000052686
resolver
genesymbol
H2ax
resolver
genesymbol_syn
H2a.x
resolver
genesymbol_syn
H2afx
resolver
genesymbol_syn
Hist5-2ax
resolver
uniprot_entry
H2AX_MOUSE
resolver
amino_acid_sequence
MSGRGKTGGKARAKAKSRSSRAGLQFPVGRVHRLLRKGHYAERVGAGAPVYLAAVLEYLTAEILELAGNAARDNKKTRIIPRHLQLAIRNDEELNKLLGGVTIAQGGVLPNIQAVLLPKKSSATVGPKAPAVGKKASQASQEY
uniprot
proteins
function
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. {ECO:0000269|PubMed:11740565, ECO:0000269|PubMed:11934988, ECO:0000269|PubMed:12034884, ECO:0000269|PubMed:12447390, ECO:0000269|PubMed:12660252, ECO:0000269|PubMed:12689589, ECO:0000269|PubMed:12792649, ECO:0000269|PubMed:12914700, ECO:0000269|PubMed:12914701, ECO:0000269|PubMed:14530383, ECO:0000269|PubMed:15574327, ECO:0000269|PubMed:15580272, ECO:0000269|PubMed:15589157, ECO:0000269|PubMed:15610743, ECO:0000269|PubMed:15632067}.
uniprot
proteins
mass_dalton
15143
uniprot
proteins
mutagenesis
MUTAGEN 6; /note="K->A: No effect on radiosensitivity; when associated with A-10, A-14 and A-16."; /evidence="ECO:0000269|PubMed:20488183"; MUTAGEN 10; /note="K->A: No effect on radiosensitivity; when associated with A-6, A-14 and A-16."; /evidence="ECO:0000269|PubMed:20488183"; MUTAGEN 14; /note="K->A: No effect on radiosensitivity; when associated with A-6, A-10 and A-16."; /evidence="ECO:0000269|PubMed:20488183"; MUTAGEN 16; /note="K->A: No effect on radiosensitivity; when associated with A-6, A-10 and A-14."; /evidence="ECO:0000269|PubMed:20488183"; MUTAGEN 37; /note="K->A: Increased radiosensitivity. No effect on phosphorylation after DNA damage. No effect on Ser-140 phosphorylation, nor on TP53BP1 recruitment to DNA double-strand breaks."; /evidence="ECO:0000269|PubMed:20488183"; MUTAGEN 37; /note="K->R: No effect on phosphorylation after DNA damage, but increased radiosensitivity. Further increase in radiosensitivity; when associated with A-140."; /evidence="ECO:0000269|PubMed:20488183"; MUTAGEN 119..120; /note="KK->AA: Complete loss of ubiquitination and increased radiosensitivity."; /evidence="ECO:0000269|PubMed:20488183"; MUTAGEN 137; /note="S->A: Increased genomic instability and radiosensitivity; when associated with A-140."; /evidence="ECO:0000269|PubMed:12914701"; MUTAGEN 140; /note="S->A: Increased genomic instability and radiosensitivity; when associated with A-137. Reduced homologous recombination. No effect on Lys-40 acetylation. Further increase in radiosensitivity; when associated with R-37."; /evidence="ECO:0000269|PubMed:12914701, ECO:0000269|PubMed:15610743, ECO:0000269|PubMed:20488183
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on Ser-140 (to form gamma-H2AX or H2AX139ph) in response to DNA double strand breaks (DSBs) generated by exogenous genotoxic agents, by stalled replication forks, by meiotic recombination events and during 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) first occurs at synaptonemal complexes during leptotene and is an ATM-dependent response to the formation of programmed DSBs by SPO11. Ser-140 phosphorylation (H2AX139ph) subsequently occurs at unsynapsed regions of both autosomes and the XY bivalent during zygotene and is ATR- and BRCA1-dependent. 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) at sites of DNA-recombination requires 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). Phosphorylated by VRK1 (By similarity). {ECO:0000250|UniProtKB:P16104, ECO:0000269|PubMed:11242108, ECO:0000269|PubMed:11571274, ECO:0000269|PubMed:11740565, ECO:0000269|PubMed:12447390, ECO:0000269|PubMed:12660252, ECO:0000269|PubMed:14530383, ECO:0000269|PubMed:15059890, ECO:0000269|PubMed:15580272, ECO:0000269|PubMed:19092802, ECO:0000269|PubMed:7217105, ECO:0000269|PubMed:9488723}.; PTM: Monoubiquitination of Lys-120 (H2AXK119ub) by RING1 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression. 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 similarity). {ECO:0000250|UniProtKB:P16104}.; PTM: Acetylation at Lys-6 (H2AXK5ac) by KAT5 component of the NuA4 histone acetyltransferase complex promotes NBN/NBS1 assembly at the sites of DNA damage (By similarity). Acetylation at Lys-37 increases in S and G2 phases (PubMed:20488183, PubMed:7217105). This modification has been proposed to be important for DNA double-strand break repair (PubMed:20488183). {ECO:0000250|UniProtKB:P16104, ECO:0000269|PubMed:20488183, ECO:0000269|PubMed:7217105}.
uniprot
proteins
protein_family
Histone H2A family
uniprot
proteins
pubmed
11242108
uniprot
proteins
pubmed
11571274
uniprot
proteins
pubmed
11740565
uniprot
proteins
pubmed
11934988
uniprot
proteins
pubmed
12034884
uniprot
proteins
pubmed
12447390
uniprot
proteins
pubmed
12660252
uniprot
proteins
pubmed
12689589
uniprot
proteins
pubmed
12697768
uniprot
proteins
pubmed
12792649
uniprot
proteins
pubmed
12914700
uniprot
proteins
pubmed
12914701
uniprot
proteins
pubmed
14530383
uniprot
proteins
pubmed
15059890
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15574327
uniprot
proteins
pubmed
15580272
uniprot
proteins
pubmed
15589157
uniprot
proteins
pubmed
15610743
uniprot
proteins
pubmed
15632067
uniprot
proteins
pubmed
19092802
uniprot
proteins
pubmed
2041781
uniprot
proteins
pubmed
20488183
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23039116
uniprot
proteins
pubmed
23806337
uniprot
proteins
pubmed
30272023
uniprot
proteins
pubmed
30746471
uniprot
proteins
pubmed
30949703
uniprot
proteins
pubmed
7217105
uniprot
proteins
pubmed
7407044
uniprot
proteins
pubmed
7774939
uniprot
proteins
pubmed
9488723
uniprot
proteins
sequence_length
143
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11242108, ECO:0000269|PubMed:11571274, ECO:0000269|PubMed:11740565, ECO:0000269|PubMed:12034884, ECO:0000269|PubMed:12447390, ECO:0000269|PubMed:15589157}. Chromosome {ECO:0000269|PubMed:11242108, ECO:0000269|PubMed:11571274, ECO:0000269|PubMed:12034884, ECO:0000269|PubMed:15059890, ECO:0000269|PubMed:15589157, ECO:0000269|PubMed:23039116, ECO:0000269|PubMed:30272023, ECO:0000269|PubMed:30746471, ECO:0000269|PubMed:30949703}.
uniprot
proteins