FB2024_02 , released April 23, 2024
Gene: Dmel\cn
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General Information
Symbol
Dmel\cn
Species
D. melanogaster
Name
cinnabar
Annotation Symbol
CG1555
Feature Type
FlyBase ID
FBgn0000337
Gene Model Status
Stock Availability
Enzyme Name (EC)
kynurenine 3-monooxygenase (1.14.13.9)
Gene Summary
cinnabar (cn) encodes the enzyme that synthesizes 3-hydroxykynurenine (3-HK) as part of the kynurenine pathway of tryptophan degradation. 3-HK is an intermediate product in the formation of ommochromes, the brown pigments in the fly eye, and thus cn loss of function mutant flies exhibit altered eye color. Several kynurenine pathway metabolites are neuroactive and have been linked to the pathogenesis of neurodegenerative disorders. [Date last reviewed: 2018-09-06] (FlyBase Gene Snapshot)
Also Known As

KMO

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
2-57
RefSeq locus
NT_033778 REGION:7782797..7785067
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (8 terms)
Molecular Function (2 terms)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
enables FAD binding
inferred from electronic annotation with InterPro:IPR002938
inferred from electronic annotation with InterPro:IPR027545
inferred from biological aspect of ancestor with PANTHER:PTN001417860
inferred from sequence or structural similarity with UniProtKB:O15229
traceable author statement
Biological Process (5 terms)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
Terms Based on Predictions or Assertions (5 terms)
CV Term
Evidence
References
traceable author statement
inferred from biological aspect of ancestor with PANTHER:PTN001417860
inferred from sequence or structural similarity with UniProtKB:Q86PM2
inferred from electronic annotation with InterPro:IPR027545
traceable author statement
inferred from electronic annotation with InterPro:IPR027545
Cellular Component (1 term)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000350492
inferred from sequence or structural similarity with UniProtKB:O88867
Protein Family (UniProt)
Belongs to the aromatic-ring hydroxylase family. KMO subfamily. (A1Z746)
Catalytic Activity (EC/Rhea)
kynurenine 3-monooxygenase activity
H(+) + L-kynurenine + NADPH + O2 = 3-hydroxy-L-kynurenine + H2O + NADP(+) (1.14.13.9)
RHEA 20545:
Summaries
Gene Snapshot
cinnabar (cn) encodes the enzyme that synthesizes 3-hydroxykynurenine (3-HK) as part of the kynurenine pathway of tryptophan degradation. 3-HK is an intermediate product in the formation of ommochromes, the brown pigments in the fly eye, and thus cn loss of function mutant flies exhibit altered eye color. Several kynurenine pathway metabolites are neuroactive and have been linked to the pathogenesis of neurodegenerative disorders. [Date last reviewed: 2018-09-06]
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 hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Required for synthesis of quinolinic acid.
(UniProt, A1Z746)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
cn: cinnabar
Eye color bright red, like v or st. Ocelli colorless. Eye color darkens with age, but ocelli remain colorless. Larval Malpighian tubes pale yellow (Beadle, 1937, Genetics 22: 587-611). cn defective in ommochrome synthesis; blocks conversion of kynurenine to 3-hydroxykynurenine, which has been identified as the cn+ hormone (Butenandt, Weidel, and Schlossberger, 1949, Z. Naturforsch. 4b: 242-44). cn homozygotes devoid of kynurenine 3-hydroxylase activity (Ghosh and Forrest, 1967, Genetics 55: 423-31). Enzyme activity proportional to the number of doses of cn+; cn+ therefore concluded to be the structural gene for kynurenine 3-hydroxylase (EC 1.14.13.9) (Sullivan, Kitos, and Sullivan, 1973, Genetics 75: 651-61). Also cn defective in the uptake of kynurenine by eye discs and Malpighian tubules, where it is normally converted to 3-hydroxykynurenine (Sullivan, Grillo, Kitos, 1974, J. Exp. Zool. 188: 225-34). Nonautonomous in development of pigment of transplanted eye disks (Beadle and Ephrussi, 1936, Genetics 21: 230); however, ethyl methanesulfonate-induced mutants recovered as mosaics in homozygous red background (Paton and Sullivan, 1978, Biochem. Genet. 16: 855-65); furthermore, even though st has no detectable 3-hydroxykynurenine, it is able to rescue cn in transplants (Phillips, Simmons, and Bowman, 1970, Biochem. Genet. 4: 481-87). Enzyme activity developmentally regulated with a peak of activity in early third instar and a five-fold higher peak in the second half of pupal development (Sullivan et al.). Heterozygotes in all pairwise combinations of 13 ethyl methanesulfonate-induced alleles exhibit mutant phenotype (Paton and Sullivan, 1978). RK1.
cnrbr
An unstable amorphic allele that reverts with frequency of 3 x 10-3 (Valade del Rio, 1974, DIS 51: 22); also induces reversions of cn1 and cn2 alleles on homologous chromosome in heterozygotes; some of the revertants themselves mutate back to cnrbr (Valade del Rio, 1982, Experientia 38: 790-92).
Gene Model and Products
Number of Transcripts
1
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\cn 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 A1Z746)

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

Mutation in sequenced strain: deletion (removes 3' end); see allele report cn[1].

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

Gene model reviewed during 5.55

Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0344723
1790
465
Additional Transcript Data and Comments
Reported size (kB)

2.2, 1.8 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0311059
52.9
465
8.82
Polypeptides with Identical Sequences

There is only one protein coding transcript and one polypeptide associated with this gene

Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Crossreferences
InterPro - A database of protein families, domains and functional sites
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\cn 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).

1.95

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

The 1.8 and 2.2 kb cn transcripts are detected in mid-larval through pupal stages, with the highest levels in mid-pupal stages. No expression is detected in newly emerged adults. The 1.8 kb transcript is dominant in larvae, while the 2.2 kb transcript is dominant in pupae.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
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\cn 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
FlyExpress - Embryonic expression images (BDGP data)
  • Stages(s) 11-12
  • Stages(s) 13-16
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 228 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 7 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of cn
Transgenic constructs containing regulatory region of cn
Aberrations (Deficiencies and Duplications) ( 153 )
Inferred from experimentation ( 153 )
Gene disrupted in
Inferred from location ( 0 )
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) (3)
12 of 14
Yes
Yes
 
1  
1 of 14
No
No
1 of 14
No
No
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (3)
12 of 14
Yes
Yes
1 of 14
No
No
1 of 14
No
No
Mus musculus (laboratory mouse) (3)
11 of 14
Yes
Yes
1 of 14
No
No
1 of 14
No
No
Xenopus tropicalis (Western clawed frog) (2)
11 of 13
Yes
Yes
1 of 13
No
No
Danio rerio (Zebrafish) (4)
12 of 14
Yes
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (3)
12 of 14
Yes
Yes
5 of 14
No
Yes
1 of 14
No
No
Anopheles gambiae (African malaria mosquito) (2)
11 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (16)
4 of 13
Yes
Yes
4 of 13
Yes
Yes
3 of 13
No
Yes
3 of 13
No
Yes
3 of 13
No
Yes
3 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
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) (3)
11 of 13
Yes
Yes
1 of 13
No
No
1 of 13
No
No
Schizosaccharomyces pombe (Fission yeast) (2)
1 of 12
Yes
No
1 of 12
Yes
Yes
Escherichia coli (enterobacterium) (4)
5 of 11
Yes
Yes
2 of 11
No
No
1 of 11
No
No
1 of 11
No
No
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:cn. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (1)
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 ( 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.
    Dmel gene
    Ortholog showing functional complementation
    Supporting References
    Interactions
    Summary of Physical Interactions
    esyN Network Diagram
    Interactions Browser
    Summary of Genetic Interactions
    esyN Network Diagram
    Show/hide secondary interactors 
    (data from AllianceMine provided by esyN)
    esyN Network Key:
    Suppression
    Enhancement

    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.
    Pathways
    Signaling Pathways (FlyBase)
    Metabolic Pathways
    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
    Linkouts
    KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
    Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    2R
    Recombination map
    2-57
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    43E16-43E16
    Limits computationally determined from genome sequence between P{PZ}l(2)0849208492 and P{EP}CanB2EP774
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    43E6-43E8
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Notes
    Stocks and Reagents
    Stocks (2,974)
    Genomic Clones (16)
     

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

    cDNA Clones (2)
     

    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

            A modified Dmau\mariner element marked with a wild-type allele of cn is capable of mediating germ-line transformation of A.aegypti.

            Cloning and characterisation of the cn region.

            Lesions in cn block pigmentation in the eye, ocelli, tubule and fat body.

            Heterozygotes in all pairwise combinations of 13 EMS-induced alleles exhibit mutant phenotype. Ethyl methanesulfonate-induced mutants can be recovered as mosaics in homozygous red background.

            cn mutants are defective in the uptake of kynurenine by eye discs and Malpighian tubules, where it is normally converted to 3-hydroxykynurenine.

            Kynurenine 3-hydroxylase activity proportional to the number of doses of cn+; cn+ therefore concluded to be the structural gene for the enzyme. Enzyme activity is developmentally regulated with a peak of activity in early third instar and a five-fold higher peak in the second half of pupal development.

            Even though st has no detectable 3-hydroxykynurenine, it is able to rescue cn mutants in transplants.

            cn homozygotes are devoid of kynurenine 3-hydroxylase activity.

            cn mutants are defective in ommochrome synthesis; blocks conversion of kynurenine to 3-hydroxykynurenine, which has been identified as the cn+ hormone.

            Larval Malpighian tubes are pale yellow.

            Nonautonomous in development of pigment of transplanted eye discs.

            Eye color bright red, like v or st mutants. Ocelli colorless. Eye color darkens with age, but ocelli remain colorless.

            Relationship to Other Genes
            Source for database merge of
            Additional comments

            The white eye colour of the A.aegypti khw mutant (caused by a mutation in Aaeg\KH) is partially complemented by D.melanogaster cn. The cn gene acts in a semi-dominant manner.

            The white eye colour of the WE strain is caused by a mutation in its kynurenine hydroxylase gene, the wild type cn gene is capable of complementing this mutation. The cn promoter is recognised and the two introns are apparently correctly spliced.

            Nomenclature History
            Source for database identify of

            Source for identity of: cn CG1555

            Nomenclature comments
            Etymology
            Synonyms and Secondary IDs (6)
            Datasets (0)
            Study focus (0)
            Experimental Role
            Project
            Project Type
            Title
            Study result (0)
            Result
            Result Type
            Title
            External Crossreferences and Linkouts ( 56 )
            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
            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
            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
            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)
            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.
            Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
            Reactome Metabolic Pathways - An open-source, open access, manually curated and peer-reviewed metabolic pathway database.
            References (203)