FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Gene: Dmel\Hph
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General Information
Symbol
Dmel\Hph
Species
D. melanogaster
Name
HIF prolyl hydroxylase
Annotation Symbol
CG44015
Feature Type
FlyBase ID
FBgn0264785
Gene Model Status
Stock Availability
Enzyme Name (EC)
hypoxia-inducible factor-proline dioxygenase (1.14.11.29)
Gene Summary
HIF prolyl hydroxylase (Hph) encodes the prolyl-4 hydroxylase that hydroxylases proline 850a of the product of sima, which is the alpha-subunit of the hypoxia inducible factor (HIF). The product of Hph regulates growth through both independent and dependent mechanisms of the product of sima. [Date last reviewed: 2019-03-07] (FlyBase Gene Snapshot)
Also Known As

fatiga, fga, l(3)02255, PHD

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
3-47.5
RefSeq locus
NT_033777 REGION:5257037..5269507
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (13 terms)
Molecular Function (6 terms)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (6 terms)
CV Term
Evidence
References
Biological Process (6 terms)
Terms Based on Experimental Evidence (6 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from high throughput mutant phenotype
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN004393218
Cellular Component (1 term)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
located_in nucleoplasm
inferred from direct assay
Terms Based on Predictions or Assertions (0 terms)
Gene Group (FlyBase)
Protein Family (UniProt)
-
Catalytic Activity (EC/Rhea)
hypoxia-inducible factor-proline dioxygenase activity
L-prolyl-[hypoxia-inducible factor alpha subunit] + 2-oxoglutarate + O2 = trans-4-hydroxy-L-prolyl-[hypoxia-inducible factor alpha subunit] + succinate + CO2 (1.14.11.29)
RHEA 48400:
Summaries
Gene Snapshot
HIF prolyl hydroxylase (Hph) encodes the prolyl-4 hydroxylase that hydroxylases proline 850a of the product of sima, which is the alpha-subunit of the hypoxia inducible factor (HIF). The product of Hph regulates growth through both independent and dependent mechanisms of the product of sima. [Date last reviewed: 2019-03-07]
Gene Group (FlyBase)
PEPTIDYL-PROLINE DIOXYGENASES -
Peptidyl-proline dioxygenases catalyze the hydroxylation of peptidyl L-proline to peptidyl hydroxy-L-proline, where 2-oxoglutarate and one other act as hydrogen or electron donors with incorporation of one atom of oxygen into each donor.
Summary (Interactive Fly)

oxygen sensor - a specific prolyl-4-hydroxylases required for hydroxylation of key prolyl residues in the HIFα sequence - Fe (II) and 2-oxoglutarate dependent dioxygenase superfamily protein that uses O2 as a co-substrate for catalysis - involved in tracheal development, oogenesis and drives cell growth downstream of Cyclin D

Gene Model and Products
Number of Transcripts
4
Number of Unique Polypeptides
3

Please see the JBrowse view of Dmel\Hph 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 Q8SX21)

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

Gene model reviewed during 5.47

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

Gene model reviewed during 5.53

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0334275
2337
325
FBtr0334274
1607
278
FBtr0334276
2496
478
FBtr0344333
3171
478
Additional Transcript Data and Comments
Reported size (kB)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0306390
36.3
325
6.87
FBpp0306389
30.6
278
6.67
FBpp0306391
52.6
478
8.01
FBpp0310716
52.6
478
8.01
Polypeptides with Identical Sequences

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

478 aa isoforms: Hph-PC, Hph-PD
Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Hph 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).

0.52

Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
organism

Comment: maternally deposited

RT-PCR
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

The Hph-RA and Hph-RB transcripts are detected at all stages of development by RT-PCR but only Hph-RB is significantly upregulated in adults. Hph-RB but not Hph-RA is induced by hypoxia.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
located_in nucleoplasm
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\Hph 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
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
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
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 35 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 10 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Hph
Transgenic constructs containing regulatory region of Hph
Aberrations (Deficiencies and Duplications) ( 7 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (8)
10 of 14
Yes
Yes
10 of 14
Yes
Yes
1  
9 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1  
1 of 14
No
No
1 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) (8)
10 of 14
Yes
Yes
10 of 14
Yes
Yes
9 of 14
No
Yes
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
Mus musculus (laboratory mouse) (7)
10 of 14
Yes
Yes
10 of 14
Yes
Yes
8 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
Xenopus tropicalis (Western clawed frog) (6)
9 of 13
Yes
Yes
8 of 13
No
Yes
8 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Danio rerio (Zebrafish) (8)
10 of 14
Yes
Yes
10 of 14
Yes
Yes
9 of 14
No
Yes
7 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
Caenorhabditis elegans (Nematode, roundworm) (1)
10 of 14
Yes
Yes
Anopheles gambiae (African malaria mosquito) (7)
9 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (3)
1 of 13
Yes
Yes
1 of 13
Yes
No
1 of 13
Yes
No
Saccharomyces cerevisiae (Brewer's yeast) (0)
Schizosaccharomyces pombe (Fission yeast) (0)
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:Hph. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (6)
2 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 1 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 1 )
    Allele
    Disease
    Interaction
    References
    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
    Interaction Browsers

    Please see the Physical Interaction reports below for full details
    RNA-RNA
    Physical Interaction
    Assay
    References
    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
    Linkouts
    DroID - A comprehensive database of gene and protein interactions.
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Pathways
    Signaling Pathways (FlyBase)
    Metabolic Pathways
    FlyBase
    External Links
    External Data
    Linkouts
    Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
    Class of Gene
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    3R
    Recombination map
    3-47.5
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    82F7-82F8
    Limits computationally determined from genome sequence between P{PZ}l(3)0273302733 and P{EP}EP974
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    Location based on deficiency mapping with Df(3R)3-4.
    82F4-82F7
    (determined by in situ hybridisation)
    82F3-82F6
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Location
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (17)
    Genomic Clones (31)
    cDNA Clones (23)
     

    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
    Antibody Information
    Laboratory Generated Antibodies
     
    Commercially Available Antibodies
     
    Cell Line Information
    Publicly Available Cell Lines
     
      Other Stable Cell Lines
       
        Other Comments

        sima protein nuclear localization is affected in Hph mutant embryos.

        Renamed annotation (CR31541) in release 3 of the genome annotation.

        A mutation in Hph causes major defects in embryonic tracheal development.

        Relationship to Other Genes
        Source for database merge of

        Source for merge of: CG1114 CG14665

        Source for merge of: Hph l(3)02255

        Source for merge of: Hph anon- EST:Posey69

        Source for merge of: Hph l(3)S030304

        Source for merge of: Hph l(3)82Fe

        Source for merge of: Hph CR31541

        Additional comments

        l(3)L3051 may correspond to Hph: the P{lacW}l(3)L3051L3051 insertion maps within the transcription unit.

        Annotations CG31543 and CR31541 merged as CG44015 in release 5.47 of the genome annotation; CR31541 corresponds to alternative 3' UTR of CG31543. Merge supported by RNA-seq junction data.

        P{PZ}Hph02255 is inserted upstream of Hph.

        Annotations CG1114, CG14665 merged as CG31543 in release 3 of the genome annotation.

        Nomenclature History
        Source for database identify of

        Source for identity of: Hph CG1114

        Nomenclature comments
        Etymology
        Synonyms and Secondary IDs (32)
        Reported As
        Symbol Synonym
        CG2676
        CR31541
        Dm.egl-9
        anon-EST:Posey69
        l(3)82Fe
        l(3)S030304
        Secondary FlyBase IDs
        • FBgn0264652
        • FBgn0086689
        • FBgn0028167
        • FBgn0051543
        • FBgn0037306
        • FBgn0027674
        • FBgn0010773
        • FBgn0037308
        • FBgn0013577
        • FBgn0037309
        Datasets (0)
        Study focus (0)
        Experimental Role
        Project
        Project Type
        Title
        Study result (0)
        Result
        Result Type
        Title
        External Crossreferences and Linkouts ( 73 )
        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 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/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.
        BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
        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
        KEGG Genes - Molecular building blocks of life in the genomic space.
        MARRVEL_MODEL - MARRVEL (model organism gene)
        Linkouts
        Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
        DroID - A comprehensive database of gene and protein interactions.
        Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
        FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
        Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
        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
        Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
        References (125)