P84243
uniprot
P84243
canonical
amino_acid_sequence
MARTKQTARKSTGGKAPRKQLATKAARKSAPSTGGVKKPHRYRPGTVALREIRRYQKSTELLIRKLPFQRLVREIAQDFKTDLRFQSAAIGALQEASEAYLVGLFEDTNLCAIHAKRVTIMPKDIQLARRIRGERA
uniprot
proteins
disease_involvement
DISEASE: Glioma (GLM) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269|PubMed:22286061, ECO:0000269|PubMed:22286216, ECO:0000269|PubMed:23539269}. Note=The gene represented in this entry is involved in disease pathogenesis. H3F3A mutations affecting residues involved in post-translational modifications of histone H3.3 are recurrent in malignant, aggressive gliomas including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG) (PubMed:22286061, PubMed:22286216). The mechanism through which mutations lead to tumorigenesis involves altered histones methylation, impaired regulation of Polycomb repressive complex 2 (PRC2) activity, and aberrant epigenetic regulation of gene expression (PubMed:23539183, PubMed:23539269, PubMed:23603901). {ECO:0000269|PubMed:22286061, ECO:0000269|PubMed:22286216, ECO:0000269|PubMed:23539183, ECO:0000269|PubMed:23539269, ECO:0000269|PubMed:23603901}.; DISEASE: Bryant-Li-Bhoj neurodevelopmental syndrome 1 (BRYLIB1) [MIM:619720]: An autosomal dominant disorder predominantly characterized by global developmental delay, impaired intellectual development, poor or absent speech, and delayed motor milestones. Clinical manifestations are highly variable, including abnormal head shape, dysmorphic facial features, oculomotor abnormalities, feeding problems, and non-specific brain imaging abnormalities. Additional features may include hearing loss, seizures, short stature, and mild skeletal defects. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}. Note=The disease is caused by variants affecting the gene represented in this entry. BRYLIB1 is caused by variants in H3-3A. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}.; DISEASE: Bryant-Li-Bhoj neurodevelopmental syndrome 2 (BRYLIB2) [MIM:619721]: An autosomal dominant disorder predominantly characterized by global developmental delay, impaired intellectual development, poor or absent speech, and delayed motor milestones. Clinical manifestations are highly variable, including abnormal head shape, dysmorphic facial features, oculomotor abnormalities, feeding problems, and non-specific brain imaging abnormalities. Additional features may include hearing loss, seizures, short stature, and mild skeletal defects. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}. Note=The disease is caused by variants affecting the gene represented in this entry. BRYLIB2 is caused by variants in H3-3B. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}.; DISEASE: Note=H3F3A and H3F3B mutations affecting residues involved in post-translational modifications of histone H3.3 are implicated in the pathogenesis of some bone and cartilage neoplasms. Mutations have been found with high prevalence in chondroblastoma and giant cell tumors of bone, and with low frequency in osteosarcoma, conventional chondrosarcoma and clear cell chondrosarcoma. Chondroblastoma samples frequently carry a H3F3B mutation affecting residue Lys-37 (H3K36), although H3F3A is mutated in some cases. Most giant cell tumors of bone harbor H3F3A mutations affecting residue Gly-35 (H3G34). {ECO:0000269|PubMed:24162739}.
uniprot
proteins
function
FUNCTION: Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. 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. {ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:15776021, ECO:0000269|PubMed:16258499}.
uniprot
proteins
mass_dalton
15328
uniprot
proteins
mutagenesis
MUTAGEN 6; /note="Q->A: Abolished serotonylation by TGM2."; /evidence="ECO:0000269|PubMed:30867594"; MUTAGEN 43; /note="R->K: Reduced binding of histone H1 to histone H3.3-containing nucleosomes."; /evidence="ECO:0000269|PubMed:27016736"; MUTAGEN 106..107; /note="ED->AA: Loss of interaction with DNAJC9, but not with other histone chaperones, such as ASF1A, MCCM2, NASP or SPT2."; /evidence="ECO:0000269|PubMed:33857403
uniprot
proteins
post_translational_modification
PTM: Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability. {ECO:0000269|PubMed:11242053, ECO:0000269|PubMed:15345777, ECO:0000269|PubMed:15471871, ECO:0000269|PubMed:16185088, ECO:0000269|PubMed:16267050, ECO:0000269|PubMed:16457588, ECO:0000269|PubMed:16497732, ECO:0000269|PubMed:17194708, ECO:0000269|PubMed:19520870, ECO:0000269|PubMed:23415232, ECO:0000269|PubMed:7309716}.; PTM: Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription. {ECO:0000269|PubMed:15345777, ECO:0000269|PubMed:15471871, ECO:0000269|PubMed:16497732, ECO:0000269|PubMed:16567635}.; PTM: Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters. {ECO:0000269|PubMed:15345777, ECO:0000269|PubMed:15471871, ECO:0000269|PubMed:16185088, ECO:0000269|PubMed:16267050, ECO:0000269|PubMed:16457588, ECO:0000269|PubMed:16497732, ECO:0000269|PubMed:17194708, ECO:0000269|PubMed:17898714, ECO:0000269|PubMed:18077460, ECO:0000269|PubMed:18079182}.; PTM: Specifically enriched in modifications associated with active chromatin such as methylation at Lys-5 (H3K4me), Lys-37 and Lys-80. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me), which are linked to gene repression, are underrepresented. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication. {ECO:0000269|PubMed:10464286, ECO:0000269|PubMed:11242053, ECO:0000269|PubMed:11856369, ECO:0000269|PubMed:12560483, ECO:0000269|PubMed:15525939, ECO:0000269|PubMed:15681610, ECO:0000269|PubMed:15851689, ECO:0000269|PubMed:16185088, ECO:0000269|PubMed:16267050, ECO:0000269|PubMed:16457588, ECO:0000269|PubMed:16497732, ECO:0000269|PubMed:17189264, ECO:0000269|PubMed:17194708, ECO:0000269|PubMed:22387026, ECO:0000269|PubMed:7309716}.; PTM: Phosphorylated at Thr-4 (H3T3ph) by VRK1 (PubMed:31527692). Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase (PubMed:15681610, PubMed:16185088). Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin. Phosphorylation on Ser-32 (H3S31ph) is specific to regions bordering centromeres in metaphase chromosomes. {ECO:0000269|PubMed:10464286, ECO:0000269|PubMed:11242053, ECO:0000269|PubMed:11856369, ECO:0000269|PubMed:12560483, ECO:0000269|PubMed:15681610, ECO:0000269|PubMed:15684425, ECO:0000269|PubMed:15851689, ECO:0000269|PubMed:16185088, ECO:0000269|PubMed:16267050, ECO:0000269|PubMed:16457588, ECO:0000269|PubMed:16497732, ECO:0000269|PubMed:17194708, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:19783980, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:20850016, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:7309716}.; PTM: Monoubiquitinated at Lys-15 (H3K14ub), Lys-19 (H3K18ub) and Lys-24 (H3K23ub) by UHRF1 and HLTF at hemimethylated DNA sites following DNA replication, promoting recruitment of DNMT1 DNA methyltransferase and replication-coupled DNA methylation maintenance (PubMed:27595565, PubMed:29053958). Monoubiquitinated at Lys-15 (H3K14ub) by G2E3: H3K14ub represents a specific tag for heterochromatin formation by facilitating the deposition of H3K9me3 (PubMed:41094145). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination (By similarity). Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation (By similarity). This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (By similarity). {ECO:0000250|UniProtKB:P84245, ECO:0000269|PubMed:27595565, ECO:0000269|PubMed:29053958, ECO:0000269|PubMed:41094145}.; PTM: Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression. {ECO:0000269|PubMed:27735137}.; PTM: Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes. {ECO:0000269|PubMed:21925322}.; PTM: Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis. {ECO:0000250|UniProtKB:P68433}.; PTM: Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes (PubMed:29211711). It gives a specific tag for epigenetic transcription activation (PubMed:29211711). Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair (PubMed:27436229). {ECO:0000269|PubMed:27436229, ECO:0000269|PubMed:29211711}.; PTM: Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802, PubMed:34874266). Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L (PubMed:34874266). H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac) (PubMed:30257210). {ECO:0000269|PubMed:29480802, ECO:0000269|PubMed:30257210, ECO:0000269|PubMed:34874266}.; PTM: Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594). {ECO:0000269|PubMed:30867594}.; PTM: Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (PubMed:32273471). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity). {ECO:0000250|UniProtKB:P84245, ECO:0000269|PubMed:32273471}.; PTM: Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription. {ECO:0000269|PubMed:31645732}.
uniprot
proteins
protein_family
Histone H3 family
uniprot
proteins
pubmed
10464286
uniprot
proteins
pubmed
11242053
uniprot
proteins
pubmed
11856369
uniprot
proteins
pubmed
12560483
uniprot
proteins
pubmed
14718166
uniprot
proteins
pubmed
15345777
uniprot
proteins
pubmed
15471871
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15498874
uniprot
proteins
pubmed
15525939
uniprot
proteins
pubmed
15681610
uniprot
proteins
pubmed
15684425
uniprot
proteins
pubmed
15776021
uniprot
proteins
pubmed
15851689
uniprot
proteins
pubmed
16185088
uniprot
proteins
pubmed
16258499
uniprot
proteins
pubmed
16267050
uniprot
proteins
pubmed
16457588
uniprot
proteins
pubmed
16497732
uniprot
proteins
pubmed
16567635
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17189264
uniprot
proteins
pubmed
17194708
uniprot
proteins
pubmed
17898714
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18066052
uniprot
proteins
pubmed
18077460
uniprot
proteins
pubmed
18079182
uniprot
proteins
pubmed
19520870
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19783980
uniprot
proteins
pubmed
20228790
uniprot
proteins
pubmed
20504901
uniprot
proteins
pubmed
20850016
uniprot
proteins
pubmed
21925322
uniprot
proteins
pubmed
22195965
uniprot
proteins
pubmed
22286061
uniprot
proteins
pubmed
22286216
uniprot
proteins
pubmed
22387026
uniprot
proteins
pubmed
22389435
uniprot
proteins
pubmed
22483618
uniprot
proteins
pubmed
22901803
uniprot
proteins
pubmed
23415232
uniprot
proteins
pubmed
23539183
uniprot
proteins
pubmed
23539269
uniprot
proteins
pubmed
23603901
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24162739
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24590075
uniprot
proteins
pubmed
24681537
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
27016736
uniprot
proteins
pubmed
27105113
uniprot
proteins
pubmed
27105115
uniprot
proteins
pubmed
27174990
uniprot
proteins
pubmed
27392148
uniprot
proteins
pubmed
27436229
uniprot
proteins
pubmed
27595565
uniprot
proteins
pubmed
27735137
uniprot
proteins
pubmed
28067913
uniprot
proteins
pubmed
28190768
uniprot
proteins
pubmed
28497810
uniprot
proteins
pubmed
2859593
uniprot
proteins
pubmed
29053958
uniprot
proteins
pubmed
29211711
uniprot
proteins
pubmed
29480802
uniprot
proteins
pubmed
30154464
uniprot
proteins
pubmed
30257210
uniprot
proteins
pubmed
3031613
uniprot
proteins
pubmed
30867594
uniprot
proteins
pubmed
31527692
uniprot
proteins
pubmed
31542297
uniprot
proteins
pubmed
31645732
uniprot
proteins
pubmed
32273471
uniprot
proteins
pubmed
32911480
uniprot
proteins
pubmed
33268356
uniprot
proteins
pubmed
33857403
uniprot
proteins
pubmed
34545082
uniprot
proteins
pubmed
34874266
uniprot
proteins
pubmed
34876591
uniprot
proteins
pubmed
34961760
uniprot
proteins
pubmed
35939806
uniprot
proteins
pubmed
41094145
uniprot
proteins
pubmed
7309716
uniprot
proteins
pubmed
8586426
uniprot
proteins
sequence_length
136
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus. Chromosome {ECO:0000269|PubMed:34876591}.
uniprot
proteins