FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Gene: Dmel\His3.3A
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General Information
Symbol
Dmel\His3.3A
Species
D. melanogaster
Name
Histone H3.3A
Annotation Symbol
CG5825
Feature Type
FlyBase ID
FBgn0014857
Gene Model Status
Stock Availability
Gene Summary
Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes and is specifically enriched in modifications associated with active chromatin. 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. (UniProt, C0HL66)
Contribute a Gene Snapshot for this gene.
Also Known As

H3.3, H3.3A, histone H3.3, His3.3, PH3

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
2-15
RefSeq locus
NT_033779 REGION:5055058..5056149
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (12 terms)
Molecular Function (4 terms)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
enables DNA binding
non-traceable author statement
inferred from electronic annotation with InterPro:IPR000164, InterPro:IPR007125
inferred from biological aspect of ancestor with PANTHER:PTN008967730
inferred from electronic annotation with InterPro:IPR000164
inferred from biological aspect of ancestor with PANTHER:PTN008967730
Biological Process (4 terms)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN008967730
inferred from biological aspect of ancestor with PANTHER:PTN008517672
inferred from biological aspect of ancestor with PANTHER:PTN008517672
non-traceable author statement
Cellular Component (4 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
part_of nucleosome
inferred from direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
is_active_in kinetochore
inferred from biological aspect of ancestor with PANTHER:PTN008517672
part_of nucleosome
inferred from biological aspect of ancestor with PANTHER:PTN008967730
non-traceable author statement
inferred from electronic annotation with InterPro:IPR000164
is_active_in nucleus
inferred from biological aspect of ancestor with PANTHER:PTN008967730
Gene Group (FlyBase)
Protein Family (UniProt)
Belongs to the histone H3 family. (C0HL66)
Summaries
Protein Function (UniProtKB)
Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes and is specifically enriched in modifications associated with active chromatin. 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.
(UniProt, C0HL66)
Summary (Interactive Fly)

H3 histone subtype - deposition is coupled to transcription and continues while a gene is active - histone replacement suggests a mechanism to maintain both the structure of chromatin and access to DNA at active genes

Gene Model and Products
Number of Transcripts
3
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\His3.3A for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Structure
Protein 3D structure   (Predicted by AlphaFold)   (AlphaFold entry C0HL66)

If you don't see a structure in the viewer, refresh your browser.
Model Confidence:
  • Very high (pLDDT > 90)
  • Confident (90 > pLDDT > 70)
  • Low (70 > pLDDT > 50)
  • Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Experimentally Determined Structures
Crossreferences
Comments on Gene Model

Low-frequency RNA-Seq exon junction(s) not annotated.

Gene model reviewed during 5.46

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0079010
848
136
FBtr0333536
926
136
FBtr0333537
772
136
Additional Transcript Data and Comments
Reported size (kB)

0.9 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0078649
15.3
136
11.83
FBpp0305717
15.3
136
11.83
Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

136 aa isoforms: His3.3A-PA, His3.3A-PC, His3.3A-PD
Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Subunit Structure (UniProtKB)

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 Daxx (via C-terminus) (PubMed:28320872). Interacts with Nasp (PubMed:36930688).

(UniProt, C0HL66)
Post Translational Modification

Phosphorylation at Ser-11 by aurB/ial during mitosis and meiosis is crucial for chromosome condensation and cell-cycle progression. Phosphorylation at Ser-11 by JIL-1 during interphase is linked to gene activation and restricts the formation of heterochromatin at inappropriate sites. Phosphorylation at Ser-11 is enriched on male X chromosome compared to the autosome.

Acetylation is generally linked to gene activation. Acetylated on Lys-15 during prophase I of meiosis. Phosphorylation of H2A 'Thr-119' is a prerequisite for H3 Lys-15 acetylation. Acetylation on Lys-15 is enriched on male X chromosome compared to the autosome.

Methylation at Lys-5 or Lys-80 is generally associated with active chromatin. Methylation at Lys-80 by gpp occurs at low levels in specific developmental stages and tissues undergoing active cell division, and at highest levels in epidermal cells undergoing differentiation.

(UniProt, C0HL66)
Crossreferences
InterPro - A database of protein families, domains and functional sites
Linkouts
Sequences Consistent with the Gene Model
Nucleotide / Polypeptide Records
 
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\His3.3A using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Expression Data
Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

1.85

Transcript Expression
northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

His3.3A is strongly transcribed in the testes.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
No Assay Recorded
Stage
Tissue/Position (including subcellular localization)
Reference
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

Antibodies against His3.3 protein stain uniformly over the polytene chromosomes. His3.3 protein staining is seen in meiotic prophase chromatin of primary spermatocytes. One or two strongly staining foci were observed in each nucleus. The distribution of label coincides with the location of some of the Y-chromosomal lampbrush loops. At this stage His3 protein is observed mainly in the autosomal chromatin. In postmeiotic stages, His3.3 protein is observed in the protein body while the His3 protein is found mainly in the chromatin. During spermatid elongation, His3.3 protein is deposited in chromatin. At subsequent stages no major differences were observed in the distribution of His3 protein and His3.3 protein. In post-elongation spermatid cysts, the pattern of staining changes from an even distribution to a dispersed pattern. In mature sperm, no staining is observed.

Marker for
 
Subcellular Localization
CV Term
Evidence
References
part_of nucleosome
inferred from direct assay
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\His3.3A in JBrowse
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 10 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 40 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of His3.3A
Transgenic constructs containing regulatory region of His3.3A
Aberrations (Deficiencies and Duplications) ( 1 )
Inferred from experimentation ( 1 )
Inferred from location ( 5 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (22)
12 of 14
Yes
Yes
2  
7 of 14
No
Yes
6 of 14
No
Yes
6 of 14
No
Yes
2  
6 of 14
No
Yes
1  
6 of 14
No
No
6 of 14
No
No
6 of 14
No
Yes
2  
6 of 14
No
Yes
6 of 14
No
Yes
2  
6 of 14
No
Yes
6 of 14
No
Yes
6 of 14
No
No
6 of 14
No
No
1  
5 of 14
No
No
3 of 14
No
No
3 of 14
No
Yes
2 of 14
No
No
1  
2 of 14
No
No
17  
2 of 14
No
No
2 of 14
No
No
1 of 14
No
Yes
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (14)
11 of 14
Yes
Yes
8 of 14
No
Yes
6 of 14
No
No
5 of 14
No
No
5 of 14
No
Yes
5 of 14
No
No
5 of 14
No
No
5 of 14
No
Yes
4 of 14
No
No
3 of 14
No
Yes
2 of 14
No
No
2 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
Mus musculus (laboratory mouse) (18)
12 of 14
Yes
Yes
6 of 14
No
Yes
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
Yes
6 of 14
No
No
6 of 14
No
No
5 of 14
No
Yes
3 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
Xenopus tropicalis (Western clawed frog) (36)
10 of 13
Yes
Yes
9 of 13
No
Yes
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
4 of 13
No
No
3 of 13
No
Yes
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
1 of 13
No
No
Danio rerio (Zebrafish) (19)
13 of 14
Yes
Yes
10 of 14
No
Yes
10 of 14
No
Yes
6 of 14
No
No
5 of 14
No
Yes
5 of 14
No
Yes
5 of 14
No
No
4 of 14
No
No
3 of 14
No
Yes
3 of 14
No
No
2 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (24)
11 of 14
Yes
Yes
8 of 14
No
Yes
8 of 14
No
Yes
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
6 of 14
No
No
5 of 14
No
No
4 of 14
No
No
2 of 14
No
No
2 of 14
No
Yes
2 of 14
No
No
2 of 14
No
No
2 of 14
No
Yes
Anopheles gambiae (African malaria mosquito) (11)
10 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (14)
8 of 13
Yes
No
8 of 13
Yes
No
8 of 13
Yes
No
8 of 13
Yes
No
7 of 13
No
No
7 of 13
No
No
7 of 13
No
Yes
6 of 13
No
Yes
5 of 13
No
No
4 of 13
No
No
3 of 13
No
No
3 of 13
No
No
2 of 13
No
No
2 of 13
No
No
Saccharomyces cerevisiae (Brewer's yeast) (3)
10 of 13
Yes
Yes
3 of 13
No
No
2 of 13
No
No
1  
Schizosaccharomyces pombe (Fission yeast) (4)
10 of 12
Yes
Yes
10 of 12
Yes
Yes
3 of 12
No
Yes
3 of 12
No
No
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:His3.3A. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (25)
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
11 of 13
4 of 13
4 of 13
3 of 13
Human Disease Associations
FlyBase Human Disease Model Reports
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 1 )
Potential Models Based on Orthology ( 1 )
Human Ortholog
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 8 )
Disease Associations of Human Orthologs (via DIOPT v9.1 and OMIM)
Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
Functional Complementation Data
Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
Interactions
Summary of Physical Interactions
Summary of Genetic Interactions
Interaction Browsers

Please look at the allele data for full details of the genetic interactions
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
External Data
Subunit Structure (UniProtKB)
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 Daxx (via C-terminus) (PubMed:28320872). Interacts with Nasp (PubMed:36930688).
(UniProt, C0HL66 )
Linkouts
BioGRID - A database of protein and genetic interactions.
DroID - A comprehensive database of gene and protein interactions.
MIST (protein-protein) - An integrated Molecular Interaction Database
Pathways
Class of Gene
Genomic Location and Detailed Mapping Data
Chromosome (arm)
2L
Recombination map
2-15
Cytogenetic map
Sequence location
FlyBase Computed Cytological Location
Cytogenetic map
Evidence for location
25C3-25C3
Limits computationally determined from genome sequence between P{lacW}vkgk16721&P{lacW}Cg25Ck00405 and P{lacW}l(2)k11206k11206
Experimentally Determined Cytological Location
Cytogenetic map
Notes
References
Experimentally Determined Recombination Data
Location
Left of (cM)
Right of (cM)
Notes
Stocks and Reagents
Stocks (16)
Genomic Clones (12)
 

Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

cDNA Clones (202)
 

Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.

cDNA clones, fully sequenced
BDGP DGC clones
Other clones
    Drosophila Genomics Resource Center cDNA clones

    For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

    cDNA Clones, End Sequenced (ESTs)
    RNAi and Array Information
    Linkouts
    DRSC - Results frm RNAi screens
    Antibody Information
    Laboratory Generated Antibodies
     
    Commercially Available Antibodies
     
    Cell Line Information
    Publicly Available Cell Lines
     
      Other Stable Cell Lines
       
        Other Comments

        The canonical "H3.2" histone (His3, present in multiple copies in the genome as part of the repeating histone gene unit) and variant "His3.3" histone (encoded by His3.3A and His3.3B) forms can functionally replace each other. Cells are able to divide and differentiate when H3.2 is entirely absent but is replaced by S phase-expressed His3.3.

        Cells that contain a non-methylatable residue instead of K4 in all canonical and variant H3 genes are competent to respond to major developmental signaling pathways by activating target gene expression, although their proliferative capacity is slowed down relative to wild type.

        Nucleosomes containing His3.3A protein but not His3 protein are specifically assembled in paternal chromatin before the first round of DNA replication in the fertilised egg.

        RNAi generated by PCR using primers directed to this gene causes a cell growth and viability phenotype when assayed in Kc167 and S2R+ cells.

        dsRNA made from templates generated with primers directed against this gene tested in RNAi screen for effects on Kc167 and S2R+ cell morphology.

        RNAi screen using dsRNA made from templates generated with primers directed against this gene causes a phenotype when assayed in Kc167 and S2R+ cells: cells become round and detached.

        Replication independent deposition of His3.3A occurs at particular loci, including active rDNA arrays.

        His3.3A has been cloned and sequenced.

        The histone H3.3 replacement variant is encoded by two genes, His3.3A and His3.3B, in D.melanogaster. These genes encode exactly the same protein but are widely divergent in their untranslated regions.

        Relationship to Other Genes
        Source for database merge of
        Additional comments
        Nomenclature History
        Source for database identify of
        Nomenclature comments
        Etymology
        Synonyms and Secondary IDs (16)
        Reported As
        Symbol Synonym
        Name Synonyms
        Secondary FlyBase IDs
          Datasets (0)
          Study focus (0)
          Experimental Role
          Project
          Project Type
          Title
          Study result (0)
          Result
          Result Type
          Title
          External Crossreferences and Linkouts ( 66 )
          Sequence Crossreferences
          NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
          GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
          GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
          RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
          UniProt/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.
          UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
          UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information
          Other crossreferences
          AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.
          DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
          EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
          FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
          FlyMine - An integrated database for Drosophila genomics
          InterPro - A database of protein families, domains and functional sites
          KEGG Genes - Molecular building blocks of life in the genomic space.
          MARRVEL_MODEL - MARRVEL (model organism gene)
          Linkouts
          BioGRID - A database of protein and genetic interactions.
          Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
          DroID - A comprehensive database of gene and protein interactions.
          DRSC - Results frm RNAi screens
          Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
          FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
          FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
          Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
          Flygut - An atlas of the Drosophila adult midgut
          FlyMet - A comprehensive tissue-specific metabolomics resource for Drosophila.
          iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
          Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
          MIST (protein-protein) - An integrated Molecular Interaction Database
          References (160)