CG8353

UniProt ID: Q9VLR2
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

CG8353 encodes a 170-residue, single-domain zinc-dependent cytidine deaminase of the small-chain (homotetrameric) CDA class, one of three tandem fly paralogs (with CG8360 and CG8349) in the PANTHER cytidine deaminase subfamily that contains human CDA and yeast CDD1. It retains the three zinc-ligand cysteines and the catalytic glutamate of the family, and by descent from characterised cytidine deaminases is expected to hydrolytically deaminate cytidine and 2'-deoxycytidine to uridine and 2'-deoxyuridine plus ammonia in the cytosol, a step of pyrimidine nucleoside salvage and catabolism. Its activity, substrate preference, oligomeric state and localisation have not been measured directly in Drosophila; RNAi knockdown in the eye enhances the toxicity of expanded CGG-repeat RNA in a fly model of fragile X-associated tremor/ataxia syndrome.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004126 cytidine deaminase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: Cytidine deaminase activity is inherited from PAINT node PTN000182087 and is the core function.
Reason: CG8353 sits in PANTHER PTHR11644:SF2 with human CDA, mouse Cda and yeast CDD1, all of which deaminate cytidine experimentally; the PAINT IBD at PTN000182087 is ancestral to the subfamily, and the family review scopes GO:0004126 to SF2. Target-specific evidence of loss is absent: the alignment to human CDA shows retention of the zinc-ligand cysteines C78, C112, C115 and the proton-donor E80. No fly enzyme assay exists, so substrate preference (cytidine vs 2'-deoxycytidine) is inferred.
Supporting Evidence:
file:DROME/CG8353/CG8353-bioinformatics/RESULTS.md
CG8353 retains all three zinc-ligand cysteines (C78, C112, C115) and the catalytic glutamate E80
file:DROME/CG8353/CG8353-uniprot.txt
DR PANTHER; PTHR11644:SF2; CYTIDINE DEAMINASE; 1.
file:human/CDA/CDA-uniprot.txt
This enzyme scavenges exogenous and endogenous cytidine and
GO:0004126 cytidine deaminase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic call agrees with the phylogenetic inference and the conserved active site.
Reason: The combined IEA rests on the tetrameric cytidine deaminase signature (IPR006262/TIGR01354), which CG8353 matches, and agrees with the IBA row for the same term. The conserved Cys3 zinc site and E80 proton donor support catalytic competence.
Supporting Evidence:
file:DROME/CG8353/CG8353-uniprot.txt
DR NCBIfam; TIGR01354; cyt_deam_tetra; 1.
file:DROME/CG8353/CG8353-bioinformatics/RESULTS.md
CG8353 retains all three zinc-ligand cysteines (C78, C112, C115) and the catalytic glutamate E80
GO:0005737 cytoplasm
IEA
GO_REF:0000117 		TOO GENERAL
Summary: True but entailed by the accepted cytosol annotation.
Reason: CG8353 is a soluble single-domain enzyme with no signal peptide or transmembrane feature, and the IBA cytosol row (accepted here) already places it more precisely. Cytoplasm adds nothing beyond that.
Supporting Evidence:
file:DROME/CG8353/CG8353-bioinformatics/RESULTS.md
The UniProt entry contains no signal peptide or transmembrane feature.
GO:0005829 cytosol
IBA
GO_REF:0000033 		ACCEPT
Summary: Cytosolic location inherited from PAINT node PTN000182087, whose seeds include human CDA.
Reason: Human CDA, a seed of the PAINT node and a member of the same SF2 subfamily, is experimentally cytosolic. CG8353 lacks any targeting signal or membrane segment, so nothing argues against the inherited cytosolic placement. Not tested directly in flies.
Supporting Evidence:
file:DROME/CG8353/CG8353-uniprot.txt
DR PANTHER; PTHR11644:SF2; CYTIDINE DEAMINASE; 1.
file:DROME/CG8353/CG8353-bioinformatics/RESULTS.md
The UniProt entry contains no signal peptide or transmembrane feature.
GO:0006217 deoxycytidine catabolic process
IBA
GO_REF:0000033 		ACCEPT
Summary: Deamination of 2'-deoxycytidine is the catalysed step of this process.
Reason: The enzyme itself performs the step (deamination of 2'-deoxycytidine to 2'-deoxyuridine), which is the reaction curated for SF2 members such as human CDA. The PAINT curator placed this process at the same node as the activity.
Supporting Evidence:
file:human/CDA/CDA-uniprot.txt
Reaction=2'-deoxycytidine + H2O + H(+) = 2'-deoxyuridine + NH4(+);
file:DROME/CG8353/CG8353-uniprot.txt
DR PANTHER; PTHR11644:SF2; CYTIDINE DEAMINASE; 1.
GO:0008270 zinc ion binding
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: The catalytic zinc ligands are conserved; zinc binding is a cofactor property of the deaminase.
Reason: C78, C112 and C115 align with the three catalytic zinc cysteines of human CDA, and the PIRSR zinc features of the entry mark the same residues. Zinc binding is real but ancillary to the deaminase activity.
Supporting Evidence:
file:DROME/CG8353/CG8353-bioinformatics/RESULTS.md
CG8353 retains all three zinc-ligand cysteines (C78, C112, C115)
file:DROME/CG8353/CG8353-uniprot.txt
DR InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd.
GO:0016787 hydrolase activity
IEA
GO_REF:0000002 		TOO GENERAL
Summary: True but entailed by the accepted cytidine deaminase activity.
Reason: Cytidine deaminase activity (accepted above) is a hydrolase activity acting on carbon-nitrogen bonds in cyclic amidines, so the generic hydrolase term adds no information.
Supporting Evidence:
file:DROME/CG8353/CG8353-uniprot.txt
DR InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd.
GO:0042802 identical protein binding
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: Self-association is expected for a small-chain tetrameric CDA but is not measured for CG8353.
Reason: CG8353 has the single-domain architecture of the homotetrameric CDA class (TIGR01354), in which the active site is completed across subunits; human CDA in the same subfamily is a crystallographic homotetramer. The ARBA call is therefore biologically plausible but peripheral to the catalytic function and untested in flies.
Supporting Evidence:
file:DROME/CG8353/CG8353-uniprot.txt
DR NCBIfam; TIGR01354; cyt_deam_tetra; 1.
file:human/CDA/CDA-uniprot.txt
SUBUNIT: Homotetramer.
GO:0046109 uridine biosynthetic process
IBA
GO_REF:0000033 		ACCEPT
Summary: Cytidine deamination directly produces uridine.
Reason: The catalysed reaction (cytidine + H2O -> uridine + NH4+) is itself a uridine-forming step, so the enzyme does the work of this process; the PAINT curator placed it at PTN000182087 with the activity. It does not imply a role in de novo pyrimidine synthesis.
Supporting Evidence:
file:human/CDA/CDA-uniprot.txt
Reaction=cytidine + H2O + H(+) = uridine + NH4(+);
file:DROME/CG8353/CG8353-uniprot.txt
DR PANTHER; PTHR11644:SF2; CYTIDINE DEAMINASE; 1.
GO:0055086 nucleobase-containing small molecule metabolic process
IEA
GO_REF:0000117 		TOO GENERAL
Summary: Ancestor of the accepted deoxycytidine catabolic and uridine biosynthetic processes.
Reason: GO:0055086 is an ancestor (via nucleoside metabolic process) of both GO:0006217 and GO:0046109, which are accepted for this gene, so this ARBA term is true but uninformative.
Supporting Evidence:
file:DROME/CG8353/CG8353-bioinformatics/RESULTS.md
The PAINT IBD node PTN000182087 (cytidine deaminase activity, cytosol, deoxycytidine catabolic process, uridine biosynthetic process)
GO:0072527 pyrimidine-containing compound metabolic process
IEA
GO_REF:0000117 		TOO GENERAL
Summary: Ancestor of the accepted deoxycytidine catabolic and uridine biosynthetic processes.
Reason: GO:0072527 is an ancestor (via pyrimidine nucleoside metabolic process) of both GO:0006217 and GO:0046109, which are accepted here.
Supporting Evidence:
file:human/CDA/CDA-uniprot.txt
This enzyme scavenges exogenous and endogenous cytidine and
GO:1901135 carbohydrate derivative metabolic process
IEA
GO_REF:0000117 		TOO GENERAL
Summary: Ancestor of the accepted nucleoside processes; nucleosides are carbohydrate derivatives.
Reason: GO:1901135 is an ancestor of GO:0006217 and GO:0046109 (accepted here); it carries no information beyond them.
Supporting Evidence:
file:human/CDA/CDA-uniprot.txt
This enzyme scavenges exogenous and endogenous cytidine and

Core Functions

Zinc-dependent hydrolytic deamination of cytidine and 2'-deoxycytidine to uridine and 2'-deoxyuridine in the cytosol, inherited from the PTHR11644:SF2 cytidine deaminase subfamily and supported by a conserved Cys3 zinc site and catalytic glutamate.

Molecular Function:
cytidine deaminase activity
Directly Involved In:
uridine biosynthetic process deoxycytidine catabolic process
Cellular Locations:
cytosol
Supporting Evidence:
  • file:DROME/CG8353/CG8353-bioinformatics/RESULTS.md
    CG8353 retains all three zinc-ligand cysteines (C78, C112, C115) and the catalytic glutamate E80
  • file:DROME/CG8353/CG8353-uniprot.txt
    DR PANTHER; PTHR11644:SF2; CYTIDINE DEAMINASE; 1.
  • file:human/CDA/CDA-uniprot.txt
    This enzyme scavenges exogenous and endogenous cytidine and

References

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Suggested Questions for Experts

Q: Do the three tandem fly CDA paralogs (CG8353, CG8360, CG8349) differ in substrate preference (cytidine, 2'-deoxycytidine, nucleoside analogues) or tissue of expression, or are they redundant?

Suggested Experiments

Experiment: Express recombinant CG8353 and measure kcat/Km for cytidine and 2'-deoxycytidine, with C78A/E80A mutants as controls; determine oligomeric state by SEC-MALS.

Deep Research

Falcon

(CG8353-deep-research-falcon.md)

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📚 Additional Documentation

Notes

(CG8353-notes.md)

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Bioinformatics Results

(RESULTS.md)

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📄 View Raw YAML

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