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Histone H3.3



Mus musculus (Mouse)
Reviewed-Annotation score: -Experimental evidence at protein leveli


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.By similarity

GO - Molecular functioni

GO - Biological processi

  • cell proliferation Source: MGI
  • chromatin silencing at rDNA Source: Reactome
  • DNA replication-independent nucleosome assembly Source: Ensembl
  • embryo implantation Source: MGI
  • male gonad development Source: MGI
  • multicellular organism growth Source: MGI
  • muscle cell differentiation Source: MGI
  • negative regulation of chromosome condensation Source: MGI
  • nucleosome assembly Source: GO_Central
  • nucleus organization Source: MGI
  • oogenesis Source: MGI
  • osteoblast differentiation Source: MGI
  • pericentric heterochromatin assembly Source: MGI
  • positive regulation of cell growth Source: Ensembl
  • regulation of centromere complex assembly Source: MGI
  • single fertilization Source: MGI
  • spermatid development Source: MGI
  • spermatogenesis Source: MGI
  • telomeric heterochromatin assembly Source: MGI


Molecular functionDNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-1221633 Meiotic Synapsis
R-MMU-201722 Formation of the beta-catenin:TCF transactivating complex
R-MMU-212300 PRC2 methylates histones and DNA
R-MMU-2299718 Condensation of Prophase Chromosomes
R-MMU-2559580 Oxidative Stress Induced Senescence
R-MMU-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-MMU-427359 SIRT1 negatively regulates rRNA expression
R-MMU-427413 NoRC negatively regulates rRNA expression
R-MMU-5250924 B-WICH complex positively regulates rRNA expression
R-MMU-5578749 Transcriptional regulation by small RNAs
R-MMU-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
R-MMU-573389 NoRC negatively regulates rRNA expression
R-MMU-73728 RNA Polymerase I Promoter Opening
R-MMU-73777 RNA Polymerase I Chain Elongation
R-MMU-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-MMU-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-MMU-912497 Meiotic Recombination
R-MMU-983231 Factors involved in megakaryocyte development and platelet production

Names & Taxonomyi

Protein namesi
Recommended name:
Histone H3.3
Gene namesi
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
  • UP000000589 Componentsi: Chromosome 1, Chromosome 11

Organism-specific databases

MGIiMGI:1097686 H3f3a
MGI:1101768 H3f3b

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleosome core, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCurated
ChainiPRO_00002212512 – 136Histone H3.3Add BLAST135

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3Asymmetric dimethylarginine; by PRMT6; alternateBy similarity1
Modified residuei3Citrulline; alternateBy similarity1
Modified residuei4Phosphothreonine; by HASPIN1 Publication1
Modified residuei5Allysine; alternateBy similarity1
Modified residuei5N6,N6,N6-trimethyllysine; alternate1 Publication1
Modified residuei5N6,N6-dimethyllysine; alternate1 Publication1
Modified residuei5N6-(2-hydroxyisobutyryl)lysine; alternate1 Publication1
Modified residuei5N6-(beta-hydroxybutyryl)lysine; alternate1 Publication1
Modified residuei5N6-acetyllysine; alternate1 Publication1
Modified residuei5N6-crotonyllysine; alternate1 Publication1
Modified residuei5N6-methyllysine; alternate1 Publication1
Modified residuei7Phosphothreonine; by PKCBy similarity1
Modified residuei9Citrulline; alternate1 Publication1
Modified residuei9Symmetric dimethylarginine; by PRMT5; alternate1 Publication1
Modified residuei10N6,N6,N6-trimethyllysine; alternate2 Publications1
Modified residuei10N6,N6-dimethyllysine; alternate2 Publications1
Modified residuei10N6-(2-hydroxyisobutyryl)lysine; alternate1 Publication1
Modified residuei10N6-(beta-hydroxybutyryl)lysine; alternate1 Publication1
Modified residuei10N6-acetyllysine; alternate2 Publications1
Modified residuei10N6-crotonyllysine; alternate1 Publication1
Modified residuei10N6-methyllysine; alternate2 Publications1
Modified residuei11ADP-ribosylserine; alternateBy similarity1
Modified residuei11Phosphoserine; alternate; by AURKB, AURKC, RPS6KA3, RPS6KA4 and RPS6KA55 Publications1
Modified residuei12Phosphothreonine; by PKCBy similarity1
Modified residuei15N6-(2-hydroxyisobutyryl)lysine; alternate1 Publication1
Modified residuei15N6-(beta-hydroxybutyryl)lysine; alternate1 Publication1
Modified residuei15N6-acetyllysine; alternate3 Publications1
Modified residuei15N6-succinyllysine; alternateBy similarity1
Modified residuei18Asymmetric dimethylarginine; by CARM1; alternate3 Publications1
Modified residuei18Citrulline; alternate1 Publication1
Modified residuei19N6-(2-hydroxyisobutyryl)lysine; alternate1 Publication1
Modified residuei19N6-(beta-hydroxybutyryl)lysine; alternate1 Publication1
Modified residuei19N6-acetyllysine; alternate3 Publications1
Modified residuei19N6-butyryllysine; alternate1 Publication1
Modified residuei19N6-crotonyllysine; alternate1 Publication1
Modified residuei19N6-methyllysine; alternate1 Publication1
Modified residuei24N6-(2-hydroxyisobutyryl)lysine; alternate1 Publication1
Modified residuei24N6-(beta-hydroxybutyryl)lysine; alternate1 Publication1
Modified residuei24N6-acetyllysine; alternate3 Publications1
Modified residuei24N6-butyryllysine; alternate1 Publication1
Modified residuei24N6-crotonyllysine; alternate1 Publication1
Modified residuei24N6-methyllysine; alternate1 Publication1
Modified residuei27CitrullineBy similarity1
Modified residuei28N6,N6,N6-trimethyllysine; alternate2 Publications1
Modified residuei28N6,N6-dimethyllysine; alternate2 Publications1
Modified residuei28N6-(2-hydroxyisobutyryl)lysine; alternate1 Publication1
Modified residuei28N6-acetyllysine; alternate1 Publication1
Modified residuei28N6-butyryllysine; alternate1 Publication1
Modified residuei28N6-crotonyllysine; alternate1 Publication1
Modified residuei28N6-methyllysine; alternate2 Publications1
Modified residuei29ADP-ribosylserine; alternateBy similarity1
Modified residuei29Phosphoserine; alternate; by AURKB, AURKC and RPS6KA56 Publications1
Modified residuei32PhosphoserineBy similarity1
Modified residuei37N6,N6,N6-trimethyllysine; alternateBy similarity1
Modified residuei37N6,N6-dimethyllysine; alternate2 Publications1
Modified residuei37N6-(2-hydroxyisobutyryl)lysine; alternate1 Publication1
Modified residuei37N6-acetyllysine; alternate1 Publication1
Modified residuei37N6-butyryllysine; alternate1 Publication1
Modified residuei37N6-methyllysine; alternate2 Publications1
Modified residuei38N6-butyryllysine; alternate1 Publication1
Modified residuei38N6-methyllysine; alternateBy similarity1
Modified residuei42PhosphotyrosineBy similarity1
Modified residuei57N6,N6,N6-trimethyllysine; alternateBy similarity1
Modified residuei57N6-(2-hydroxyisobutyryl)lysine; alternate1 Publication1
Modified residuei57N6-(beta-hydroxybutyryl)lysine; alternate1 Publication1
Modified residuei57N6-acetyllysine; alternateBy similarity1
Modified residuei57N6-crotonyllysine; alternate1 Publication1
Modified residuei57N6-methyllysine; by EHMT2; alternateBy similarity1
Modified residuei57N6-succinyllysine; alternate1 Publication1
Modified residuei58PhosphoserineBy similarity1
Modified residuei65N6-(2-hydroxyisobutyryl)lysine; alternate1 Publication1
Modified residuei65N6-methyllysine; alternateBy similarity1
Modified residuei80N6,N6,N6-trimethyllysine; alternate2 Publications1
Modified residuei80N6,N6-dimethyllysine; alternate2 Publications1
Modified residuei80N6-(2-hydroxyisobutyryl)lysine; alternate1 Publication1
Modified residuei80N6-acetyllysine; alternateBy similarity1
Modified residuei80N6-butyryllysine; alternate1 Publication1
Modified residuei80N6-methyllysine; alternate2 Publications1
Modified residuei80N6-succinyllysine; alternate1 Publication1
Modified residuei81PhosphothreonineBy similarity1
Modified residuei87PhosphoserineBy similarity1
Modified residuei108PhosphothreonineBy similarity1
Modified residuei116N6-acetyllysineBy similarity1
Modified residuei123N6-(2-hydroxyisobutyryl)lysine; alternate1 Publication1
Modified residuei123N6-acetyllysine; alternateBy similarity1
Modified residuei123N6-butyryllysine; alternate1 Publication1
Modified residuei123N6-methyllysine; alternate1 Publication1
Modified residuei123N6-succinyllysine; alternateBy similarity1

Post-translational modificationi

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.6 Publications
Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.5 Publications
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.By similarity
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.9 Publications
Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. 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 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. metaphase chromosomes.10 Publications
Ubiquitinated. Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination.1 Publication
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.By similarity
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.1 Publication
Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.1 Publication
Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.1 Publication
Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation.By similarity

Keywords - PTMi

Acetylation, ADP-ribosylation, Citrullination, Hydroxylation, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases


PTM databases



Developmental stagei

Expressed throughout the cell cycle independently of DNA synthesis.1 Publication

Gene expression databases

ExpressionAtlasiP84244 baseline and differential
GenevisibleiP84244 MM


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 HIRA, a chaperone required for its incorporation into nucleosomes. Interacts with ZMYND11; when trimethylated at 'Lys-36' (H3.3K36me3).By similarity


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei32Interaction with ZMYND11By similarity1

GO - Molecular functioni

Protein-protein interaction databases

BioGridi20019626 interactors.
2001993 interactors.
IntActiP84244 39 interactors.


3D structure databases

Select the link destinations:
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum

Family & Domainsi


Specific interaction of trimethylated form at 'Lys-36' (H3.3K36me3) with ZMYND11 is mediated by the encapsulation of Ser-32 residue with a composite pocket formed by the tandem bromo-PWWP domains (By similarity). Interacts with ZMYND11; when trimethylated at 'Lys-36' (H3.3K36me3).By similarity

Sequence similaritiesi

Belongs to the histone H3 family.Curated

Phylogenomic databases

eggNOGiKOG1745 Eukaryota

Family and domain databases

Gene3Di1.10.20.101 hit
InterProiView protein in InterPro
IPR009072 Histone-fold
IPR007125 Histone_H2A/H2B/H3
IPR000164 Histone_H3/CENP-A
PANTHERiPTHR11426 PTHR11426, 1 hit
PfamiView protein in Pfam
PF00125 Histone, 1 hit
SMARTiView protein in SMART
SM00428 H3, 1 hit
SUPFAMiSSF47113 SSF47113, 1 hit
PROSITEiView protein in PROSITE
PS00322 HISTONE_H3_1, 1 hit
PS00959 HISTONE_H3_2, 1 hit


Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P84244-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
60 70 80 90 100
110 120 130
Mass (Da):15,328
Last modified:January 23, 2007 - v2

Sequence cautioni

The sequence AAH92300 differs from that shown. Reason: Frameshift at position 127.Curated
The sequence BAB27616 differs from that shown. Reason: Frameshift at position 99.Curated
The sequence BAE35387 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti75I → T in AAH21768 (PubMed:15489334).Curated1
Sequence conflicti99A → E in BAE31789 (PubMed:16141072).Curated1
Sequence conflicti99A → E in BAE30411 (PubMed:16141072).Curated1
Sequence conflicti129R → C in X91866 (PubMed:9174168).Curated1

Sequence databases

Select the link destinations:
Links Updated
X13605 mRNA Translation: CAA31940.1
Z85979 mRNA Translation: CAB06625.1
X91866 mRNA No translation available.
AK002928 mRNA Translation: BAB22464.1
AK011431 mRNA Translation: BAB27616.1 Frameshift.
AK037900 mRNA Translation: BAC29895.1
AK088075 mRNA Translation: BAC40130.1
AK135839 mRNA Translation: BAE22687.1
AK150467 mRNA Translation: BAE29584.1
AK150468 mRNA Translation: BAE29585.1
AK150591 mRNA Translation: BAE29685.1
AK150928 mRNA Translation: BAE29966.1
AK151274 mRNA Translation: BAE30261.1
AK151336 mRNA Translation: BAE30314.1
AK151451 mRNA Translation: BAE30411.1
AK151634 mRNA Translation: BAE30566.1
AK151658 mRNA Translation: BAE30586.1
AK151661 mRNA Translation: BAE30589.1
AK151869 mRNA Translation: BAE30757.1
AK152293 mRNA Translation: BAE31102.1
AK152453 mRNA Translation: BAE31231.1
AK152455 mRNA Translation: BAE31233.1
AK152623 mRNA Translation: BAE31366.1
AK152911 mRNA Translation: BAE31590.1
AK153034 mRNA Translation: BAE31666.1
AK153189 mRNA Translation: BAE31789.1
AK153239 mRNA Translation: BAE31831.1
AK153294 mRNA Translation: BAE31877.1
AK153371 mRNA Translation: BAE31939.1
AK153530 mRNA Translation: BAE32069.1
AK159615 mRNA Translation: BAE35232.1
AK159807 mRNA Translation: BAE35387.1 Frameshift.
AK159850 mRNA Translation: BAE35427.1
AK160677 mRNA Translation: BAE35953.1
AK161675 mRNA Translation: BAE36524.1
AK162040 mRNA Translation: BAE36694.1
AK163244 mRNA Translation: BAE37253.1
AK167828 mRNA Translation: BAE39850.1
AK167879 mRNA Translation: BAE39892.1
AK168197 mRNA Translation: BAE40157.1
AK168698 mRNA Translation: BAE40542.1
AK169042 mRNA Translation: BAE40831.1
AK169226 mRNA Translation: BAE40995.1
BC002268 mRNA Translation: AAH02268.1
BC012687 mRNA Translation: AAH12687.1
BC021768 mRNA Translation: AAH21768.1
BC037730 mRNA Translation: AAH37730.1
BC083353 mRNA Translation: AAH83353.1
BC088835 mRNA Translation: AAH88835.1
BC092043 mRNA Translation: AAH92043.1
BC092300 mRNA Translation: AAH92300.1 Frameshift.
BC106177 mRNA Translation: AAI06178.1
AY383567 Genomic DNA Translation: AAQ96274.1
RefSeqiNP_032236.1, NM_008210.5
NP_032237.1, NM_008211.3
XP_006532311.1, XM_006532248.2

Genome annotation databases

EnsembliENSMUST00000016703; ENSMUSP00000016703; ENSMUSG00000016559
ENSMUST00000106454; ENSMUSP00000102062; ENSMUSG00000016559
ENSMUST00000161308; ENSMUSP00000124509; ENSMUSG00000060743
ENSMUST00000162814; ENSMUSP00000125104; ENSMUSG00000060743
UCSCiuc007dwr.1 mouse

Similar proteinsi

Entry informationi

Entry nameiH33_MOUSE
AccessioniPrimary (citable) accession number: P84244
Secondary accession number(s): P06351
, P33155, Q3TW79, Q3U6D6, Q569U8, Q5HZY8, Q6TXQ5, Q8VDJ2, Q9D0H3, Q9V3W4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 23, 2007
Last modified: April 25, 2018
This is version 142 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program


Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome