FB2025_05 , released December 11, 2025
Gene: Dmel\Nos
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General Information
Symbol
Dmel\Nos
Species
D. melanogaster
Name
Nitric oxide synthase
Annotation Symbol
CG6713
Feature Type
FlyBase ID
FBgn0011676
Gene Model Status
Stock Availability
Enzyme Name (EC)
nitric-oxide synthase (NADPH) (1.14.13.39)
Gene Summary
Catalyzes the conversion of L-arginine to L-citrulline producing nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:12804606, PubMed:7568075). Truncated isoforms (isoform 3-isoform 6) are able to form intracellular complexes with the full-length protein and serve as dominant negative inhibitors of the enzyme activity. (UniProt, Q27571)
Contribute a Gene Snapshot for this gene.
Also Known As

dNOS, NO synthase, iNOS

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
2-43
RefSeq locus
NT_033779 REGION:10804274..10837511
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (24 terms)
Molecular Function (7 terms)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
inferred from direct assay
inferred from mutant phenotype
Terms Based on Predictions or Assertions (7 terms)
CV Term
Evidence
References
inferred from electronic annotation with InterPro:IPR012144
non-traceable author statement
inferred from biological aspect of ancestor with PANTHER:PTN000453956
inferred from electronic annotation with InterPro:IPR012144
enables FMN binding
inferred from biological aspect of ancestor with PANTHER:PTN000453956
enables heme binding
non-traceable author statement
inferred from electronic annotation with InterPro:IPR012144
enables NADP binding
inferred from electronic annotation with InterPro:IPR012144
inferred from sequence or structural similarity with MGI:MGI:97361
traceable author statement
inferred from sequence or structural similarity with UniProtKB:P35228
inferred from biological aspect of ancestor with PANTHER:PTN001066032
Biological Process (13 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
Terms Based on Predictions or Assertions (10 terms)
CV Term
Evidence
References
traceable author statement
inferred from biological aspect of ancestor with PANTHER:PTN001066032
inferred from biological aspect of ancestor with PANTHER:PTN002322100
traceable author statement
traceable author statement
traceable author statement
inferred from biological aspect of ancestor with PANTHER:PTN002322100
inferred from biological aspect of ancestor with PANTHER:PTN001066032
involved_in synapse assembly
traceable author statement
Cellular Component (4 terms)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
is_active_in cytosol
inferred from biological aspect of ancestor with PANTHER:PTN000453956
is_active_in nucleus
inferred from biological aspect of ancestor with PANTHER:PTN001066032
located_in peroxisome
inferred from sequence or structural similarity with UniProtKB:P35228
is_active_in plasma membrane
inferred from biological aspect of ancestor with PANTHER:PTN001066032
Protein Family (UniProt)
Belongs to the NOS family. (Q27571)
Catalytic Activity (EC/Rhea)
nitric-oxide synthase activity
2 L-arginine + 3 NADPH + 4 O2 + H(+) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H2O (1.14.13.39)
RHEA 19897:
Summaries
Gene Group (FlyBase)
MONOOXYGENASES, NAD(P)H AS ONE DONOR -
Monooxygenases, NAD(P)H as one donor, include dehydrogenases that catalyze the oxidation reduction reaction in which hydrogen or electrons are transferred from NADH or NADPH and one other donor, and one atom of oxygen is incorporated into one donor.
Protein Function (UniProtKB)
Catalyzes the conversion of L-arginine to L-citrulline producing nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:12804606, PubMed:7568075). Truncated isoforms (isoform 3-isoform 6) are able to form intracellular complexes with the full-length protein and serve as dominant negative inhibitors of the enzyme activity.
(UniProt, Q27571)
Summary (Interactive Fly)

Ca++/Calmodulin sensitive enzyme - ectopic expression of NOS at the late stages of larval development results in a decrease in cell proliferation and a reduction in the size of the adult fly's structures - regulates growth coordination during imaginal disc regeneration

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

Please see the JBrowse view of Dmel\Nos 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 Q27571)

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

Multiple transcript isoforms producing truncated protein isoforms have been postulated (FBrf0145604); since there is little supporting data, only one truncated isoform has been retained in the most recent annotation.

Gene model reviewed during 5.51

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

Gene model reviewed during 5.52

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0080188
4696
1349
FBtr0100489
4805
756
FBtr0343888
4000
1098
Additional Transcript Data and Comments
Reported size (kB)

5.0 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
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\Nos 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).

-0.68

Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
RT-PCR
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

Nos-RA (dNOS1) and Nos-RF (dNOS4) are co-expressed at all developmental stages. Expression levels of both transcripts are comparable in embryos, but expression of Nos-RF is lower in larvae and adults than is expression of Nos-RA.

Nos is expressed in adult heads but not bodies.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
enzyme assay or biochemical detection
Stage
Tissue/Position (including subcellular localization)
Reference
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
adult optic lobe | restricted

Comment: cells directly adjacent to retinal axon termini

mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
western blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

Nos protein expression is upregulated in the ring gland very late in larval development; expression is detected mostly in the corpus cardiacum at "blue gut" stage, but detectable thoughout the entire ring gland at "cleared gut" stage.

Nos protein is expressed in white prepupae in a small set of cells in the optic lobe, directly adjacent to the termini of the retinal axons. By pupal stage P6 (24 hr APF), Nos protein is expressed at a low level in the lamina, and at a high level in the medulla. This pattern continues through pharate adult stage P8 (50 hr APF), then decreases by pharate adult stage P9 (72 hr APF). No expression is observed in the optic lobe at pharate adult stage P15 (96 hr APF).

Histochemical staining for the NADPH-diaphorase activity of Nos protein was used to detect Nos protein in all imaginal discs, imaginal rings, histoblasts and the larval brain. Protein is first detected early in third instar larvae. Staining becomes more intense as development proceeds and in late third instar larvae and early pupal stages a very specific and reproducible pattern of staining is seen in each disc. Nos protein reaches its highest levels in imaginal discs at the time when the cell cycle slows down and then gradually decreases through early pupal development. The pattern of staining in leg discs is described in detail.

Marker for
 
Subcellular Localization
CV Term
Evidence
References
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\Nos 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
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 ( 17 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 23 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Nos
Transgenic constructs containing regulatory region of Nos
Aberrations (Deficiencies and Duplications) ( 3 )
Inferred from experimentation ( 3 )
Inferred from location ( 8 )
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) (6)
12 of 14
Yes
Yes
11 of 14
No
Yes
1  
10 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1  
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (6)
12 of 14
Yes
Yes
11 of 14
No
Yes
10 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Mus musculus (laboratory mouse) (6)
12 of 14
Yes
Yes
10 of 14
No
Yes
9 of 14
No
Yes
2  
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Xenopus tropicalis (Western clawed frog) (7)
8 of 13
Yes
Yes
7 of 13
No
Yes
6 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Danio rerio (Zebrafish) (7)
12 of 14
Yes
Yes
9 of 14
No
Yes
9 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (3)
1 of 14
Yes
No
1 of 14
Yes
No
1 of 14
Yes
No
Anopheles gambiae (African malaria mosquito) (9)
11 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (9)
2 of 13
Yes
No
2 of 13
Yes
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Saccharomyces cerevisiae (Brewer's yeast) (5)
2 of 13
Yes
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Schizosaccharomyces pombe (Fission yeast) (5)
2 of 12
Yes
No
2 of 12
Yes
No
2 of 12
Yes
No
1 of 12
No
No
1 of 12
No
No
Escherichia coli (enterobacterium) (1)
4 of 11
Yes
No
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:Nos. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (3)
4 of 13
3 of 13
3 of 13
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 4 )
    Potential Models Based on Orthology ( 0 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 3 )
    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.
    Homo sapiens (Human)
    Gene name
    Score
    OMIM
    OMIM Phenotype
    DO term
    Complementation?
    Transgene?
    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
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    DroID - A comprehensive database of gene and protein interactions.
    MIST (genetic) - An integrated Molecular Interaction Database
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Pathways
    Signaling Pathways (FlyBase)
    Metabolic Pathways
    FlyBase
    External Links
    FlyCyc Pathways - Pathways from a BioCyc PGDB for Dmel
    KEGG Metabolic Pathways - A collection of manually drawn metabolic pathway maps representing knowledge of molecular interaction, reaction and relation networks.
    Reactome Metabolic Pathways - An open-source, open access, manually curated and peer-reviewed metabolic pathway database.
    External Data
    Class of Gene
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    2L
    Recombination map
    2-43
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    32B1-32B1
    Limits computationally determined from genome sequence between P{PZ}dbf1 and P{lacW}SCARk03107
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    Experimentally Determined Recombination Data
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (131)
    Genomic Clones (45)
    cDNA Clones (4)
     

    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)
    BDGP DGC clones
    Other clones
    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

        Alternative transcription start sites and alternative splice sites are used to generate a large number of different mRNAs from the Nos gene. Some of these mRNAs encode truncated Nos polypeptides that can form heterodimers with full-length Nos protein (NOS1) and strongly inhibit its enzymatic activity when co-expressed in cultured mammalian cells.

        Nos has a suggested role in the developing imaginal eye disc via interaction with the Rbf pathway.

        Transcription of Nos in Malpighian tubules is stimulated by cardioacceleratory peptide 2b (capa); this is dependent on the activation of a soluble guanylate cyclase.

        Nos is expressed in imaginal discs during larval development. Inhibition of Nos activity (by injection of specific Nos inhibitors) at the late stages of larval development results in excessive cell proliferation and increased size of structures of the adult body, changes are most profound in and most often affected the leg segments. Excessive proliferation of various cell types in the eye is masked by programmed cell death in the larvae and pupae.

        Nos cDNA has been isolated, primary structure of the protein determined and enzyme activity assayed in culture cells.

        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 (22)
        Reported As
        Symbol Synonym
        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 ( 102 )
          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/Swiss-Prot - Manually annotated and reviewed 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
          FlyMine - An integrated database for Drosophila genomics
          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
          FlyCyc Pathways - Pathways 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
          KEGG Metabolic Pathways - A collection of manually drawn metabolic pathway maps representing knowledge of molecular interaction, reaction and relation networks.
          KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
          MIST (genetic) - An integrated Molecular Interaction Database
          MIST (protein-protein) - An integrated Molecular Interaction Database
          Reactome Metabolic Pathways - An open-source, open access, manually curated and peer-reviewed metabolic pathway database.
          References (194)