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Protein

Histone H3.3

Gene

h3f3a

more
Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei32 – 321Interaction with zmynd11By similarity

GO - Molecular functioni

Complete GO annotation...

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_275902. PRC2 methylates histones and DNA.
REACT_280677. formation of the beta-catenin:TCF transactivating complex.
REACT_281294. Meiotic recombination.
REACT_286446. Senescence-Associated Secretory Phenotype (SASP).
REACT_290180. Transcriptional regulation by small RNAs.
REACT_303513. Factors involved in megakaryocyte development and platelet production.
REACT_318135. Condensation of Prophase Chromosomes.
REACT_325578. SIRT1 negatively regulates rRNA Expression.
REACT_327059. NoRC negatively regulates rRNA expression.
REACT_331584. Oxidative Stress Induced Senescence.
REACT_346813. RNA Polymerase I Promoter Opening.
REACT_348706. RNA Polymerase I Chain Elongation.
REACT_352958. DNA methylation.
REACT_359431. Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone H3.3
Gene namesi
Name:h3f3a
ORF Names:zgc:56193, zgc:86731
AND
Name:h3f3b.1
ORF Names:zgc:110292
AND
Name:h3f3c
ORF Names:zgc:64222
AND
Name:h3f3d
ORF Names:zgc:56418
OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)
Taxonomic identifieri7955 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
ProteomesiUP000000437 Componentsi: Chromosome 15, Chromosome 24, Chromosome 3, Chromosome 5

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleosome core, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 136135Histone H3.3PRO_0000253956Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei3 – 31Asymmetric dimethylarginine; by PRMT6By similarity
Modified residuei4 – 41Phosphothreonine; by GSG2By similarity
Modified residuei5 – 51Allysine; alternateBy similarity
Modified residuei5 – 51N6,N6,N6-trimethyllysine; alternateBy similarity
Modified residuei5 – 51N6,N6-dimethyllysine; alternateBy similarity
Modified residuei5 – 51N6-acetyllysine; alternateBy similarity
Modified residuei5 – 51N6-methyllysine; alternateBy similarity
Modified residuei7 – 71Phosphothreonine; by PKCBy similarity
Modified residuei10 – 101N6-methylated lysineBy similarity
Modified residuei11 – 111Phosphoserine; by AURKB, AURKC, RPS6KA3, RPS6KA4 and RPS6KA5By similarity
Modified residuei12 – 121Phosphothreonine; by PKCBy similarity
Modified residuei15 – 151N6-acetyllysineBy similarity
Modified residuei18 – 181Asymmetric dimethylarginineBy similarity
Modified residuei19 – 191N6-acetyllysine; alternateBy similarity
Modified residuei19 – 191N6-methylated lysine; alternateBy similarity
Modified residuei24 – 241N6-acetyllysineBy similarity
Modified residuei28 – 281N6-acetyllysine; alternateBy similarity
Modified residuei28 – 281N6-methylated lysine; alternateBy similarity
Modified residuei29 – 291Phosphoserine; by AURKB, AURKC and RPS6KA5By similarity
Modified residuei37 – 371N6-acetyllysine; alternateBy similarity
Modified residuei37 – 371N6-methylated lysine; alternateBy similarity
Modified residuei42 – 421PhosphotyrosineBy similarity
Modified residuei58 – 581PhosphoserineBy similarity
Modified residuei65 – 651N6-methylated lysineBy similarity
Modified residuei80 – 801N6-methylated lysineBy similarity
Modified residuei81 – 811PhosphothreonineBy similarity
Modified residuei116 – 1161N6-acetyllysineBy similarity
Modified residuei123 – 1231N6-acetyllysine; alternateBy similarity
Modified residuei123 – 1231N6-methyllysine; alternateBy similarity

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 (By similarity).By similarity
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 mltk 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).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, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ6PI20.

Expressioni

Developmental stagei

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

Gene expression databases

BgeeiQ6PI20.

Interactioni

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).

Protein-protein interaction databases

BioGridi95374. 1 interaction.
STRINGi7955.ENSDARP00000125972.

Structurei

3D structure databases

ProteinModelPortaliQ6PI20.
SMRiQ6PI20. Positions 17-136.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

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

eggNOGiCOG2036.
GeneTreeiENSGT00760000118967.
HOGENOMiHOG000155290.
HOVERGENiHBG001172.
InParanoidiQ6PI20.
KOiK11253.
OMAiCHASMAR.
OrthoDBiEOG7HB5C2.
PhylomeDBiQ6PI20.
TreeFamiTF314241.

Family and domain databases

Gene3Di1.10.20.10. 1 hit.
InterProiIPR009072. Histone-fold.
IPR007125. Histone_core_D.
IPR000164. Histone_H3/CENP-A.
[Graphical view]
PANTHERiPTHR11426. PTHR11426. 1 hit.
PfamiPF00125. Histone. 1 hit.
[Graphical view]
PRINTSiPR00622. HISTONEH3.
SMARTiSM00428. H3. 1 hit.
[Graphical view]
SUPFAMiSSF47113. SSF47113. 1 hit.
PROSITEiPS00322. HISTONE_H3_1. 1 hit.
PS00959. HISTONE_H3_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q6PI20-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARTKQTARK STGGKAPRKQ LATKAARKSA PSTGGVKKPH RYRPGTVALR
60 70 80 90 100
EIRRYQKSTE LLIRKLPFQR LVREIAQDFK TDLRFQSAAI GALQEASEAY
110 120 130
LVGLFEDTNL CAIHAKRVTI MPKDIQLARR IRGERA
Length:136
Mass (Da):15,328
Last modified:January 23, 2007 - v3
Checksum:i5158ED279E6F9E1C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti50 – 501R → G in AAH45982 (Ref. 1) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC045982 mRNA. Translation: AAH45982.1.
BC049017 mRNA. Translation: AAH49017.1.
BC057444 mRNA. Translation: AAH57444.1.
BC071406 mRNA. Translation: AAH71406.1.
BC092854 mRNA. Translation: AAH92854.1.
BC152134 mRNA. Translation: AAI52135.1.
BC154269 mRNA. Translation: AAI54270.1.
RefSeqiNP_001017599.1. NM_001017599.1.
NP_956297.1. NM_200003.1.
NP_957395.1. NM_201101.1.
NP_998161.1. NM_212996.1.
XP_002664801.1. XM_002664755.4.
XP_009290278.1. XM_009292003.1.
UniGeneiDr.42924.
Dr.75577.
Dr.75603.
Dr.77073.
Dr.91654.

Genome annotation databases

EnsembliENSDART00000027623; ENSDARP00000006849; ENSDARG00000020504.
ENSDART00000047269; ENSDARP00000047268; ENSDARG00000033009.
ENSDART00000066545; ENSDARP00000066544; ENSDARG00000045248.
ENSDART00000098982; ENSDARP00000089753; ENSDARG00000068436.
ENSDART00000137017; ENSDARP00000117879; ENSDARG00000045248.
ENSDART00000146211; ENSDARP00000120344; ENSDARG00000020504.
ENSDART00000151594; ENSDARP00000125972; ENSDARG00000068436.
ENSDART00000151600; ENSDARP00000126130; ENSDARG00000068434.
GeneIDi100331798.
336231.
394076.
406269.
550262.
KEGGidre:100331798.
dre:336231.
dre:394076.
dre:406269.
dre:550262.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC045982 mRNA. Translation: AAH45982.1.
BC049017 mRNA. Translation: AAH49017.1.
BC057444 mRNA. Translation: AAH57444.1.
BC071406 mRNA. Translation: AAH71406.1.
BC092854 mRNA. Translation: AAH92854.1.
BC152134 mRNA. Translation: AAI52135.1.
BC154269 mRNA. Translation: AAI54270.1.
RefSeqiNP_001017599.1. NM_001017599.1.
NP_956297.1. NM_200003.1.
NP_957395.1. NM_201101.1.
NP_998161.1. NM_212996.1.
XP_002664801.1. XM_002664755.4.
XP_009290278.1. XM_009292003.1.
UniGeneiDr.42924.
Dr.75577.
Dr.75603.
Dr.77073.
Dr.91654.

3D structure databases

ProteinModelPortaliQ6PI20.
SMRiQ6PI20. Positions 17-136.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi95374. 1 interaction.
STRINGi7955.ENSDARP00000125972.

Proteomic databases

PRIDEiQ6PI20.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSDART00000027623; ENSDARP00000006849; ENSDARG00000020504.
ENSDART00000047269; ENSDARP00000047268; ENSDARG00000033009.
ENSDART00000066545; ENSDARP00000066544; ENSDARG00000045248.
ENSDART00000098982; ENSDARP00000089753; ENSDARG00000068436.
ENSDART00000137017; ENSDARP00000117879; ENSDARG00000045248.
ENSDART00000146211; ENSDARP00000120344; ENSDARG00000020504.
ENSDART00000151594; ENSDARP00000125972; ENSDARG00000068436.
ENSDART00000151600; ENSDARP00000126130; ENSDARG00000068434.
GeneIDi100331798.
336231.
394076.
406269.
550262.
KEGGidre:100331798.
dre:336231.
dre:394076.
dre:406269.
dre:550262.

Organism-specific databases

CTDi3020.
394076.
440093.
550262.

Phylogenomic databases

eggNOGiCOG2036.
GeneTreeiENSGT00760000118967.
HOGENOMiHOG000155290.
HOVERGENiHBG001172.
InParanoidiQ6PI20.
KOiK11253.
OMAiCHASMAR.
OrthoDBiEOG7HB5C2.
PhylomeDBiQ6PI20.
TreeFamiTF314241.

Enzyme and pathway databases

ReactomeiREACT_275902. PRC2 methylates histones and DNA.
REACT_280677. formation of the beta-catenin:TCF transactivating complex.
REACT_281294. Meiotic recombination.
REACT_286446. Senescence-Associated Secretory Phenotype (SASP).
REACT_290180. Transcriptional regulation by small RNAs.
REACT_303513. Factors involved in megakaryocyte development and platelet production.
REACT_318135. Condensation of Prophase Chromosomes.
REACT_325578. SIRT1 negatively regulates rRNA Expression.
REACT_327059. NoRC negatively regulates rRNA expression.
REACT_331584. Oxidative Stress Induced Senescence.
REACT_346813. RNA Polymerase I Promoter Opening.
REACT_348706. RNA Polymerase I Chain Elongation.
REACT_352958. DNA methylation.
REACT_359431. Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3.

Miscellaneous databases

NextBioi20811638.
PROiQ6PI20.

Gene expression databases

BgeeiQ6PI20.

Family and domain databases

Gene3Di1.10.20.10. 1 hit.
InterProiIPR009072. Histone-fold.
IPR007125. Histone_core_D.
IPR000164. Histone_H3/CENP-A.
[Graphical view]
PANTHERiPTHR11426. PTHR11426. 1 hit.
PfamiPF00125. Histone. 1 hit.
[Graphical view]
PRINTSiPR00622. HISTONEH3.
SMARTiSM00428. H3. 1 hit.
[Graphical view]
SUPFAMiSSF47113. SSF47113. 1 hit.
PROSITEiPS00322. HISTONE_H3_1. 1 hit.
PS00959. HISTONE_H3_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. NIH - Zebrafish Gene Collection (ZGC) project
    Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: SJD and WIK.
    Tissue: Embryo and Olfactory epithelium.

Entry informationi

Entry nameiH33_DANRE
AccessioniPrimary (citable) accession number: Q6PI20
Secondary accession number(s): A5PL96, Q7ZV67
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: January 23, 2007
Last modified: June 24, 2015
This is version 114 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.