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Histone H3.3

Xenopus laevis (African clawed frog)
Reviewed-Annotation score: Annotation score: 4 out of 5-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


Molecular functionDNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Histone H3.3
OrganismiXenopus laevis (African clawed frog)
Taxonomic identifieri8355 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiAmphibiaBatrachiaAnuraPipoideaPipidaeXenopodinaeXenopusXenopus

Organism-specific databases

XenbaseiXB-GENE-488762. h3f3b.

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Chromosome, Nucleosome core, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002539572 – 136Histone H3.3Add BLAST135

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3Asymmetric dimethylarginine; by PRMT6By similarity1
Modified residuei4Phosphothreonine; by GSG2By similarity1
Modified residuei5Allysine; alternateBy similarity1
Modified residuei5N6,N6,N6-trimethyllysine; alternate1 Publication1
Modified residuei5N6,N6-dimethyllysine; alternate1 Publication1
Modified residuei5N6-acetyllysine; alternateBy similarity1
Modified residuei5N6-methyllysine; alternate1 Publication1
Modified residuei7Phosphothreonine; by PKCBy similarity1
Modified residuei10N6-methylated lysine1 Publication1
Modified residuei11ADP-ribosylserine; alternateBy similarity1
Modified residuei11Phosphoserine; alternate; by AURKB, AURKC, RPS6KA3, RPS6KA4 and RPS6KA5By similarity1
Modified residuei12Phosphothreonine; by PKCBy similarity1
Modified residuei15N6-acetyllysine1 Publication1
Modified residuei18Asymmetric dimethylarginine1 Publication1
Modified residuei19N6-acetyllysine; alternateBy similarity1
Modified residuei19N6-methylated lysine; alternateBy similarity1
Modified residuei24N6-acetyllysineBy similarity1
Modified residuei28N6-acetyllysine; alternateBy similarity1
Modified residuei28N6-methylated lysine; alternateBy similarity1
Modified residuei29ADP-ribosylserine; alternateBy similarity1
Modified residuei29Phosphoserine; alternate; by AURKB, AURKC and RPS6KA5By similarity1
Modified residuei37N6-acetyllysine; alternateBy similarity1
Modified residuei37N6-methylated lysine; alternateBy similarity1
Modified residuei42PhosphotyrosineBy similarity1
Modified residuei58PhosphoserineBy similarity1
Modified residuei65N6-methylated lysineBy similarity1
Modified residuei80N6-methylated lysineBy similarity1
Modified residuei81PhosphothreonineBy similarity1
Modified residuei116N6-acetyllysineBy similarity1
Modified residuei123N6-acetyllysine; alternateBy similarity1
Modified residuei123N6-methyllysine; alternateBy similarity1

Post-translational modificationi

Acetylation is generally linked to gene activation. 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.1 Publication
Asymmetric dimethylation at Arg-18 (H3R17me2a) is linked to gene activation. 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).By similarity
Specifically enriched in modifications associated with active chromatin such as methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. 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) are linked to gene repression. 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' (By similarity).By similarity
Phosphorylated at Thr-4 (H3T3ph) by gsg2/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.By similarity
Monoubiquitinated by rag1 in lymphoid cells, monoubiquitination is required for V(D)J recombination.By similarity
Lysine deamination at Lys-5 (H3K4all) to form allysine only takes place on H3K4me3 and results in gene repression.By similarity

Keywords - PTMi

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


Developmental stagei

Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.


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 zmynd11; when trimethylated at 'Lys-36' (H3.3K36me3).By similarity


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei32Interaction with zmynd11By similarity1

GO - Molecular functioni


3D structure databases


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

Sequence similaritiesi

Belongs to the histone H3 family.Curated

Phylogenomic databases


Family and domain databases

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.

Q6PI79-1 [UniParc]FASTAAdd to basket

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110 120 130
Mass (Da):15,328
Last modified:January 23, 2007 - v3

Sequence databases

Select the link destinations:
Links Updated
BC041218 mRNA. Translation: AAH41218.1.
BC042290 mRNA. Translation: AAH42290.1.
BC042309 mRNA. Translation: AAH42309.1.
BC070966 mRNA. Translation: AAH70966.1.
BC074158 mRNA. Translation: AAH74158.1.
BC106302 mRNA. Translation: AAI06303.1.
BC123120 mRNA. Translation: AAI23121.1.
RefSeqiNP_001079375.1. NM_001085906.1.
NP_001080065.1. NM_001086596.1.
NP_001085048.1. NM_001091579.1.
NP_001086074.1. NM_001092605.1.
NP_001091902.1. NM_001098432.1.
XP_018091870.1. XM_018236381.1.
XP_018118148.1. XM_018262659.1.
XP_018119714.1. XM_018264225.1.

Genome annotation databases


Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiH33_XENLA
AccessioniPrimary (citable) accession number: Q6PI79
Secondary accession number(s): Q05AX9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: January 23, 2007
Last modified: May 10, 2017
This is version 88 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program



  1. SIMILARITY comments
    Index of protein domains and families