H2AX
entrez
3014
canonical
uniprot
P16104
canonical
ensembl
ENSG00000188486
resolver
ensp
ENSP00000364310
resolver
ensp
ENSP00000434024
resolver
enst
ENST00000375167
resolver
enst
ENST00000530167
resolver
genesymbol
H2AX
resolver
genesymbol_syn
H2AFX
resolver
hgnc
HGNC:4739
resolver
uniprot
Q4ZGJ7
resolver
uniprot
Q6IAS5
resolver
uniprot_entry
H2AX_HUMAN
resolver
uniprot_sec
Q4ZGJ7
resolver
uniprot_sec
Q6IAS5
resolver
amino_acid_sequence
MSGRGKTGGKARAKAKSRSSRAGLQFPVGRVHRLLRKGHYAERVGAGAPVYLAAVLEYLTAEILELAGNAARDNKKTRIIPRHLQLAIRNDEELNKLLGGVTIAQGGVLPNIQAVLLPKKTSATVGPKAPSGGKKATQASQEY
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:10959836, ECO:0000269|PubMed:12419185, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:17709392, ECO:0000269|PubMed:26438602}.
uniprot
proteins
mass_dalton
15145
uniprot
proteins
mutagenesis
MUTAGEN 6; /note="K->R: Decreased acetylation and reduced H2AXK119ub ubiquitination."; /evidence="ECO:0000269|PubMed:17709392"; MUTAGEN 140; /note="S->A: Impaired phosphorylation without affecting H2AXK5ac acetylation."; /evidence="ECO:0000269|PubMed:17709392"; MUTAGEN 141; /note="Q->N: Reduced phosphorylation of S-140 in response to DNA damage."; /evidence="ECO:0000269|PubMed:9488723"; MUTAGEN 143; /note="Y->F: Displays a reduced apoptotic response. S-140 phosphorylation is reduced."; /evidence="ECO:0000269|PubMed:19092802, ECO:0000269|PubMed:19234442
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by VRK1 (PubMed:31527692). 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). {ECO:0000269|PubMed:10477747, ECO:0000269|PubMed:10734083, ECO:0000269|PubMed:10959836, ECO:0000269|PubMed:11673449, ECO:0000269|PubMed:12419185, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12660252, ECO:0000269|PubMed:12697768, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:15059890, ECO:0000269|PubMed:15489221, ECO:0000269|PubMed:15613478, ECO:0000269|PubMed:17709392, ECO:0000269|PubMed:19092802, ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:22154951, ECO:0000269|PubMed:31527692, ECO:0000269|PubMed:9488723}.; PTM: 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. {ECO:0000250|UniProtKB:P27661, ECO:0000269|PubMed:18001824, ECO:0000269|PubMed:18001825, ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19203579, ECO:0000269|PubMed:22980979}.; 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 (PubMed:17709392, PubMed:26438602). 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). {ECO:0000250|UniProtKB:P27661, ECO:0000269|PubMed:17709392, ECO:0000269|PubMed:26438602}.
uniprot
proteins
protein_family
Histone H2A family
uniprot
proteins
pubmed
10477747
uniprot
proteins
pubmed
10734083
uniprot
proteins
pubmed
10959836
uniprot
proteins
pubmed
11673449
uniprot
proteins
pubmed
12419185
uniprot
proteins
pubmed
12607005
uniprot
proteins
pubmed
12660252
uniprot
proteins
pubmed
12697768
uniprot
proteins
pubmed
14627815
uniprot
proteins
pubmed
15059890
uniprot
proteins
pubmed
15201865
uniprot
proteins
pubmed
15489221
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15613478
uniprot
proteins
pubmed
16310392
uniprot
proteins
pubmed
16820410
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
17709392
uniprot
proteins
pubmed
18001824
uniprot
proteins
pubmed
18001825
uniprot
proteins
pubmed
19092802
uniprot
proteins
pubmed
19203578
uniprot
proteins
pubmed
19203579
uniprot
proteins
pubmed
19234442
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22154951
uniprot
proteins
pubmed
22980979
uniprot
proteins
pubmed
24429368
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
2587254
uniprot
proteins
pubmed
26438602
uniprot
proteins
pubmed
26721387
uniprot
proteins
pubmed
26734725
uniprot
proteins
pubmed
27715493
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
31527692
uniprot
proteins
pubmed
35849344
uniprot
proteins
pubmed
9488723
uniprot
proteins
sequence_length
143
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12419185, ECO:0000269|PubMed:12660252, ECO:0000269|PubMed:12697768, ECO:0000269|PubMed:15613478, ECO:0000269|PubMed:24429368}. Chromosome {ECO:0000269|PubMed:10959836, ECO:0000269|PubMed:11673449, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12660252, ECO:0000269|PubMed:15059890, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15613478}.
uniprot
proteins