FB2025_05 , released December 11, 2025
Gene: Dmel\r
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General Information
Symbol
Dmel\r
Species
D. melanogaster
Name
rudimentary
Annotation Symbol
CG18572
Feature Type
FlyBase ID
FBgn0003189
Gene Model Status
Stock Availability
Enzyme Name (EC)
aspartate carbamoyltransferase (2.1.3.2)
dihydroorotase (3.5.2.3)
carbamoyl-phosphate synthase (glutamine-hydrolyzing) (6.3.5.5)
Gene Summary
rudimentary (r) encodes the CAD protein that catalyzes the initial steps of de novo pyrimidine biosynthesis. r depletion results in wing malformations and pyrimidine auxotrophy. [Date last reviewed: 2019-03-14] (FlyBase Gene Snapshot)
Also Known As

Su(b), CAD, fs(1)M34

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
1-54
RefSeq locus
NC_004354 REGION:16655359..16668712
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (16 terms)
Molecular Function (11 terms)
Terms Based on Experimental Evidence (3 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from mutant phenotype
inferred from mutant phenotype
inferred from direct assay
inferred from mutant phenotype
inferred from direct assay
Terms Based on Predictions or Assertions (11 terms)
CV Term
Evidence
References
inferred from electronic annotation with InterPro:IPR002082
inferred from biological aspect of ancestor with PANTHER:PTN000150227
enables ATP binding
inferred by curator from GO:0004088
inferred from biological aspect of ancestor with PANTHER:PTN000150227
inferred by curator from GO:0004088
inferred from electronic annotation with InterPro:IPR011761
NOT enables peptidase activity
inferred from key residues with MEROPS:M38.972
Biological Process (3 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
inferred from mutant phenotype
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
Cellular Component (2 terms)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
is_active_in cytoplasm
inferred from biological aspect of ancestor with PANTHER:PTN000150222
is_active_in cytosol
inferred from biological aspect of ancestor with PANTHER:PTN000150227
Protein Family (UniProt)
-
Catalytic Activity (EC/Rhea)
carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity
hydrogencarbonate + L-glutamine + 2 ATP + H2O = carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) (6.3.5.5)
RHEA 18633: aspartate carbamoyltransferase activity
carbamoyl phosphate + L-aspartate = N-carbamoyl-L-aspartate + phosphate + H(+) (2.1.3.2)
RHEA 20013: dihydroorotase activity
(S)-dihydroorotate + H2O = N-carbamoyl-L-aspartate + H(+) (3.5.2.3)
RHEA 24296:
Summaries
Gene Snapshot
rudimentary (r) encodes the CAD protein that catalyzes the initial steps of de novo pyrimidine biosynthesis. r depletion results in wing malformations and pyrimidine auxotrophy. [Date last reviewed: 2019-03-14]
Gene Group (FlyBase)
CARBON-NITROGEN LIGASES, WITH GLUTAMINE AS AMIDO-N-DONOR -
Carbon-nitrogen ligases, with glutamine as amido-n-donor, catalyze the transfer of the amide nitrogen of glutamine to a variety of substrates.
ASPARTATE CARBAMOYLTRANSFERASES -
Aspartate carbamoyltransferases catalyze the transfer of carbamoyl group from carbamoyl phosphate onto L-aspartate.
CARBON-NITROGEN HYDROLASES OF CYCLIC AMIDES -
Carbon-Nitrogen hydrolases of cyclic amides catalyze the hydrolysis of any non-peptide carbon-nitrogen bond in a cyclic amide.
C26 NON-PEPTIDASE HOMOLOGS -
C26 non-peptidase homologs are similar in amino acid sequence to gamma-glutamyl hydrolases (C26 cysteine peptidases) but lack one or more of the expected catalytic residues. (Adapted from FBrf0239469.)
Protein Function (UniProtKB)
Multifunctional protein that encodes the first 3 enzymatic activities of the de novo pyrimidine pathway: carbamoylphosphate synthetase (CPSase; EC 6.3.5.5), aspartate transcarbamylase (ATCase; EC 2.1.3.2) and dihydroorotase (DHOase; EC 3.5.2.3). The CPSase-function is accomplished in 2 steps, by a glutamine-dependent amidotransferase activity (GATase) that binds and cleaves glutamine to produce ammonia, followed by an ammonium-dependent carbamoyl phosphate synthetase, which reacts with the ammonia, hydrogencarbonate and ATP to form carbamoyl phosphate. The endogenously produced carbamoyl phosphate is sequestered and channeled to the ATCase active site. ATCase then catalyzes the formation of carbamoyl-L-aspartate from L-aspartate and carbamoyl phosphate. In the last step, DHOase catalyzes the cyclization of carbamoyl aspartate to dihydroorotate.
(UniProt, P05990)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
r: rudimentary
thumb
r9: rudimentary-9
From Edith M. Wallace, unpublished.
Homozygotes and hemizygotes are pyrimidine auxotrophs (Nørby, 1969, Hereditas 66: 205-14). A complex locus encoding a 220 kd polypeptide containing the first three enzyme activities in the pyrimidine synthetic pathway: glutamine-dependent carbamyl phosphate synthetase [CPS (EC.2.7.2.5)] (Jarry and Falk, 1974, Mol. Gen. Genet. 135: 113-22), aspartate transcarbamylase [ATC (EC.2.1.3.2)] (Nørby, 1969), and dihydroorotase [DHO (EC.3.5.2.3)] (Rawls and Fristrom, 1975, Nature 255: 738-40). Probably exists as a homomultimer. These three activities cosediment and copurify (Brothers, Tsubota, Germeraad, and Fristrom, 1978, Biochem. Genet. 16: 321-32); also the developmental profiles of the three activities are the same, maximal in the egg, dropping until the time of hatching, increasing again during the first larval instar, and then leveling off at a low level (Mehl and Jarry, 1978, Dev. Biol. 67: 1-10); high activity in egg attributable to maternal expression. Wings of homozygous females and hemizygous males obliquely truncated posteriorly; phenotype varies from wings that are wrinkled and blistered and do not extend beyond the tip of the abdomen to normal, with intermediate phenotypes having wings truncated to various degrees but not wrinkled or blistered, or normal wings with irregularly spaced marginal hairs. Wing cells smaller than normal (Fausto-Sterling and Hsieh, 1975, Dev. Biol. 51: 269-81); oblique truncation attributed to cell death in distal portion of presumptive wing blade (Fausto-Sterling, 1980, J. Exp. Zool. 213: 383-90). Homozygous females usually sterile when crossed to r male; occasionally give a few offspring, virtually all daughters plus a few exceptional males, when outrcossed. r39 females produce many malformed eggs and unfertilized eggs with normal morphology; ovarian development often retarded or fails; yolk deposition affected; lethal effect in progeny results from generalized disturbance in differentiation 13-16 hr after fertilization at 25; surviving embryos hatch late and may produce larvae that neither move nor feed (Counce, 1956, Z. Indukt. Abstamm. Vererbungsl. 87: 482-92). Eggs produced by r9 parents fail to hatch, but can be rescued by the injection of preblastoderm eggs with cytoplasm from either fertilized or unfertilized wild-type eggs or with pyrimidine nucleosides (Okada, Kleinman, and Schneiderman, 1974, Dev. Biol. 37: 55-62). r/0 tissue in gynandromorphs produced by r/r females confined to abdomen; no such constraint when produced by r/+ females (Fausto-Sterling, 1971, Dev. Biol. 26: 452-63). Mosaic studies of Falk (1977, Dev. Biol. 58: 134-47) indicate nonautonomy of r+ within the wing and the ovary, and that normal wing and ovarian development depend on pyrimidine synthesis within those organs. Female-sterile but not truncated-wing aspect of phenotype partially alleviated by administration of cytidine during development (Bahn, 1970, DIS 45: 99); administration of 6-azauracil or 6-azauridine, competetive inhibitors of pyrimidine synthesis, causes rudimentary phenocopies [Rizki and Rizki, 1965, Science 150: 222-23; Strøman, Bahn, Nørby, and Sick, 1973, Hereditas 73: 239-46 (fig.)]. Sex-linked recessive mutants selected on the basis of inability to survive on medium deficient in pyrimidines all map to the rudimentary locus; the majority have the rudimentary phenotype, but some are phenotypcially normal and are designated subliminal alleles in the following table. Subliminal alleles exhibit strongly depressed survival on pyrimidine-free medium; standard alleles do not survive in the absence of pyrimidine; relative survival of r/+ heterozygotes varies from 5 to 70% depending on severity of allele (Falk and Nash, 1974, Mol. Gen. Genet. 131: 339-49).
rCS1: rudimentary-cold sensitive
Homozygotes raised at 16 are lethal, at 20 are rudimentary, and at 25 are wild type in phenotype; the same results are observed in rCS1/Df(1)r-D17 and rCS1/r1 heterozygotes; r1 is deficient for DHO only. Heterozygotes with r11, which is deficient for CPS, are rudimentary at all temperatures, and heterozygotes with r29 and r38, which lack ATC activity, are wild type at all temperatures. Cold-sensitive periods during embryogenesis and during organogenesis in the early pupal stage; larval stages cold stable. Activities of DHO isolated from early embryos cold sensitive; CPS exhibits reduced activity at all temperatures; ATC cold stable (Azou, Mehl, and Jarry, 1981, Dev. Biol. 84: 157-63).
Su(b): Suppressor of black
A semidominant suppressor of b; homozygotes and hemizygotes in combination with b are slightly darker than wild type, whereas heterozygotes are intermediate between b and wild type in cuticle reflectance. Su(b) by itself has no visible phenotype. Although supplementation of the medium with 6-azathymine, an inhibitor of dihydrouracil dehydrogenase, results in a dark body color in wild-type flies, it does not darken the wild-type coloration of Su(b); b. The double-mutant combination, Su(b) r, does not suppress b (Bahn and Søndergaard, 1983, Hereditas 99: 309-10), whereas su(r) Su(b); b flies have enhanced black cuticle. Unlike su(b); b, the combination Su(b); b is not sensitive to dietary β-alanine (Campbell and Sherald, 1987, DIS 66: 34).
Gene Model and Products
Number of Transcripts
3
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\r 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 P05990)

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 6.01

Gene model reviewed during 5.50

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

Annotated transcripts do not represent all supported alternative splices within 5' UTR.

Gene model reviewed during 6.02

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0089734
7057
2224
FBtr0340155
6875
2224
FBtr0340156
6946
2224
Additional Transcript Data and Comments
Reported size (kB)

7.3 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0088675
246.7
2224
6.62
FBpp0309141
246.7
2224
6.62
FBpp0309142
246.7
2224
6.62
Polypeptides with Identical Sequences

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

2224 aa isoforms: r-PA, r-PD, r-PE
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\r 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).

2.19

Transcript Expression
Additional Descriptive Data

r transcripts are initiated from 5 closely spaced transcription start sites. The relative levels of these transcripts remain constant through development.

r transcript levels are two fold higher in rhd1 mutants than in wild type.

Levels of r transcripts are reduced in rhd2 relative to wild type.

Levels of r transcripts are reduced in rhd3 relative to wild type.

Levels of r transcripts are reduced in rhd4 relative to wild type.

Levels of r transcripts are reduced in rhd5 relative to wild type.

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\r 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 ( 265 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 11 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of r
Transgenic constructs containing regulatory region of r
Aberrations (Deficiencies and Duplications) ( 76 )
Inferred from experimentation ( 76 )
Gene disrupted in
Inferred from location ( 15 )
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) (16)
14 of 14
Yes
Yes
6 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
3  
1 of 14
No
No
1 of 14
No
No
2  
1 of 14
No
No
2  
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1  
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
2  
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) (12)
14 of 14
Yes
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
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
2  
1 of 14
No
Yes
Mus musculus (laboratory mouse) (12)
14 of 14
Yes
Yes
6 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
Yes
Xenopus tropicalis (Western clawed frog) (12)
8 of 13
Yes
Yes
5 of 13
No
Yes
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
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Danio rerio (Zebrafish) (15)
14 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
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (10)
13 of 14
Yes
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Anopheles gambiae (African malaria mosquito) (7)
12 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (20)
11 of 13
Yes
Yes
4 of 13
No
Yes
3 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
Yes
1 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
Yes
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
No
1 of 13
No
Yes
Saccharomyces cerevisiae (Brewer's yeast) (14)
12 of 13
Yes
Yes
7 of 13
No
Yes
5 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
1 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
Yes
Schizosaccharomyces pombe (Fission yeast) (8)
12 of 12
Yes
Yes
7 of 12
No
Yes
4 of 12
No
Yes
1 of 12
No
No
1 of 12
No
Yes
1 of 12
No
No
1 of 12
No
Yes
1 of 12
No
Yes
Escherichia coli (enterobacterium) (14)
9 of 11
Yes
Yes
3 of 11
No
Yes
2 of 11
No
Yes
1 of 11
No
No
1 of 11
No
Yes
1 of 11
No
Yes
1 of 11
No
No
1 of 11
No
No
1 of 11
No
Yes
1 of 11
No
Yes
1 of 11
No
Yes
1 of 11
No
Yes
1 of 11
No
Yes
1 of 11
No
Yes
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:r. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (6)
1 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 ( 2 )
    Modifiers Based on Experimental Evidence ( 0 )
    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
    protein-protein
    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
    suppressible
    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
    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.
    Class of Gene
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    X
    Recombination map
    1-54
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    14F5-15A1
    Limits computationally determined from genome sequence between P{EP}EP1547EP1547 and P{EP}CG4928EP1341
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    15A1-15A2
    (determined by in situ hybridisation)
    15A-15A
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Notes

    rSu(b) has been mapped to a region 10-19.5 x 10-5 map units from the distal end of the r locus, using rX917 and r13A.

    Mapping based on large scale measurements of r-f recombination.

    Stocks and Reagents
    Stocks (21)
    Genomic Clones (15)
     

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

    cDNA Clones (10)
     

    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
      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

        Duplicate transcripts identified and eliminated during the migration of annotations from the release 5 genome assembly to the release 6 assembly.

        A conserved Glu residue in the second ATP binding site of the carbamyl phosphate synthetase domain of r plays an essential role in the feedback inhibition of the carbamyl phosphate synthetase enzyme by UTP.

        The largest intron of r includes a second gene, CG15865 that is transcribed in the opposite direction. This arrangement is preserved in the homologous genes in D.simulans.

        Loss of vein mutations cause suppression of rhohs.PSt ectopic vein phenotype and enhancement of the rhove-1 loss of vein phenotype.

        Mutants of r cause a defect in the feedback regulation of the CPSase activity of the r gene product.

        Two alleles of r that are not caused by insertions of gypsy are suppressed by mutations at su(Hw). Phenotypic suppression correlates with enhanced levels of transcription in both cases.

        Detailed molecular analysis of r indicates that transcription initiates at 5 sites within a 50bp region, that falls within a nuclease susceptible region. Additional nuclease sensitive regions in 1st exon and 1st intron coincide with insertion sites of P elements in r mutant alleles. Relative levels of 5 differently initiated messages stay the same during development. r has a previously unreported 5' exon, the 5' end of which is only 350 bp from the neighbouring, divergently transcribed gene.

        Developmental expression pattern of r has been determined.

        Scaffold attachment regions in the region surrounding r have been mapped.

        The organisation of amplified DNA, which includes the r region, in Drosophila cells resistant to 10mM N-(phosphonacetyl)-L-aspartate has been studied.

        Comparison of the r gene sequence with genes involved in the pyrimidine pathway of prokaryotes and lower eukaryotes suggests that r encodes four enzymatically different functions; glutamine amido transferase (GATase), carbamyl phosphate synthase (CPSase), dihydro-orotase (DHOase) and aspartate transcarbamylase (ATCase), which are organised on the peptide chain in the following order; NH2-GATase-CPSase-DHOase-ATCase-COOH.

        r has been cloned and sequenced.

        PALA (N-phosphonacetyl-L-aspartate) resistant Drosophila cell lines show an increase in enzyme activity encoded by r (aspartate transcarbamylase, dihydroorotase and carbamyl phosphate synthetase activity).

        The molecular organisation of the r locus has been studied.

        A cell line resistant to N-(phosphonoacetyl)-L-aspartate (PALA) shows amplification of the r gene and surrounding regions.

        The activity of the three enzymes encoded by r (carbamyl phosphate synthetase, aspartate transcarbamylase and dihydroorotase) during ovarian development has been studied.

        A study of putative regulatory mutations of the r locus supports the hypothesis that the three enzyme activities encoded by the locus (carbamyl phosphate synthase, aspartyl transcarbamylase and dihydroorotase) are part of a trifunctional polypeptide or that their genes are transcribed together as parts of a multicistronic transcript.

        Complementation units A, B, C and D correspond to units I, III, VI and VII, respectively, of FBrf0022687.

        The complementation behavior of a collection of new r alleles generated with different mutagens supports the premise that the CPSase-ATCase-DHOase complex is translated from a single mRNA.

        Complementation analysis divides a group of twelve alleles into three groups based on wing phenotype and two groups based on pyrimidine auxotrophy.

        Alleles of r reside in a number of recombinationally separable sites and display a complex pattern of interallelic interaction.

        Fine structure of the locus examined by both recombination and complementation (Carlson, 1971). Carlson defines seven complementing regions, whereas Fahmy and Fahmy (1959) recognized six, Green (1963) at least three, Falk (1976) three, and Rawls and Porter (1979) four. Region D of Rawls and Porter corresponds to regions VII and C of Carlson and Falk respectively and identifies the DHO domain; region C of Rawls and Porter corresponds to regions VI and B of Carlson and Falk and identifies the CPS domain; and region D of Rawls and Porter corresponds to region I and C of Carlson and Falk and identifies the ACT domain. The genetic map and the complementation map are roughly colinear. Noncomplementing alleles map to both the 5' and 3' ends of the gene (Carlson's numbers 5 and 6 at the 5' end and numbers 35, 37 and 42-45 at the 3' end, where numbers refer to approximate linear order of alleles on the genetic map). Complementation maps constructed using wing phenotype and survival on unsupplemented medium not identical (Falk, 1976).

        Homozygotes and hemizygotes are pyrimidine auxotrophs (Norby, 1969). A complex locus encoding a 220kD polypeptide containing the first three enzyme activities in the pyrimidine synthetic pathway: glutamine-dependent carbamyl phosphate synthetase (CPS) (Jarry and Falk, 1974), aspartate transcarbamylase (ATC) (Norby, 1969) and dihydroorotase (DHO) (Rawls and Fristrom, 1975). Probably exists as a homomultimer. These three activities cosediment and copurify (Brothers, Tsubota, Germeraad and Fristrom, 1978); also the developmental profiles of the three activities are the same, maximal in the egg, dropping until the time of hatching, increasing again during the first larval instar and then leveling off at a low level (Mehl and Jarry, 1978); high activity in egg attributable to maternal expression. Wings of homozygous females and hemizygous males obliquely truncated posteriorly; phenotype varies from wings that are wrinkled and blistered and do not extend beyond the tip of the abdomen to normal, with intermediate phenotypes having wings truncated to various degrees but not wrinkled or blistered, or normal wings with irregularly spaced marginal hairs. Wing cells smaller than normal (Fausto-Sterling and Hsieh, 1975); oblique truncation attributed to cell death in distal portion of presumptive wing blade (Fausto-Sterling, 1980). Homozygous females usually sterile when crossed to r male; occasionally give a few offspring, virtually all daughters plus a few exceptional males, when outcrossed. r39 females produce many malformed eggs and unfertilized eggs with normal morphology; ovarian development often retarded or fails; yolk deposition affected; lethal effect in progeny results from generalized disturbance in differentiation 13-16 hr after fertilization at 25oC; surviving embryos hatch late and may produce larvae that neither move nor feed (Counce, 1956). Eggs produced by r9 parents fail to hatch, but can be rescued by the injection of preblastoderm eggs with cytoplasm from either fertilized or unfertilized wild-type eggs or with pyrimidine nucleosides (Okada et al., 1974). r/0 tissue in gynandromorphs produced by r/r females confined to abdomen; no such constraint when produced by r/+ females (Fausto-Sterling, 1971). Mosaic studies of Falk (1977) indicate nonautonomy of r+ within the wing and the ovary, and that normal wing and ovarian development depend on pyrimidine synthesis within those organs. Female-sterile but not truncated-wing aspect of phenotype partially alleviated by administration of cytidine during development (Bahn, 1970); administration of 6-azauracil or 6-azauridine, competitive inhibitors of pyrimidine synthesis, causes rudimentary phenocopies (Rizki and Rizki, 1965; Stroman et al., 1973). Sex-linked recessive mutants selected on the basis of inability to survive on medium deficient in pyrimidines all map to the rudimentary locus; the majority have the rudimentary phenotype, but some are phenotypicially normal and are designated subliminal alleles. Subliminal alleles exhibit strongly depressed survival on pyrimidine-free medium; standard alleles do not survive in the absence of pyrimidine; relative survival of r/+ heterozygotes varies from 5 to 70% depending on severity of allele (Falk and Nash, 1974).

        Relationship to Other Genes
        Source for database merge of

        Source for merge of: r CG18572

        Additional comments

        Source for merge of r CG18572 was sequence comparison ( date:001104 ).

        Allele records report three classifications of complementation groups, using three different naming systems (Carlson (FBrf0022687), Falk (FBrf0029196), and Rawls and Porter (FBrf0033165)). A of FBrf0033165 corresponds to C of FBrf0029196 and I of FBrf0022687. B of FBrf0033165 corresponds to III of FBrf0022687. C of FBrf0033165 corresponds to B of FBrf0029196 and VI of FBrf0022687. D of FBrf0033165 corresponds to A of FBrf0029196 and VII of FBrf0022687.

        Nomenclature History
        Source for database identify of
        Nomenclature comments
        Etymology
        Synonyms and Secondary IDs (22)
        Reported As
        Symbol Synonym
        CG4601
        fs(1)829
        l(1)Ab
        Secondary FlyBase IDs
        • FBgn0003548
        • FBgn0026833
        • FBgn0042228
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        External Crossreferences and Linkouts ( 111 )
        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
        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
        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)
        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 - 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 (257)