CG31606

UniProt ID: Q8IPG8
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

CG31606 encodes a small (197-residue) uncharacterised protein that is restricted to the Drosophila melanogaster species group. It has a predicted cleavable N-terminal signal peptide (residues 1-18) followed by a soluble mature chain with no transmembrane segment, no ER-retention signal and no recognised protein family or domain. This suggests the protein is secreted. Orthologs are found only in melanogaster-group drosophilids, and the gene has no characterised homolog in other insects, model organisms or vertebrates. Its molecular activity, binding partners and physiological role have not been studied.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003674 molecular_function
ND
GO_REF:0000015 		ACCEPT
Summary: No molecular function is known. The ND root annotation correctly records the absence of evidence.
Reason: No gene-specific functional study exists, and no characterised relative can be used for transfer. The protein has no InterPro or PANTHER signature. Its only detectable relatives are uncharacterised Drosophila proteins that match at marginal E-values over part of the sequence. A signal peptide shows entry into the secretory pathway but says nothing about molecular activity.
Supporting Evidence:
file:DROME/CG31606/CG31606-uniprot.txt
SIGNAL 1..18
file:DROME/CG31606/CG31606-bioinformatics/rereview/RESULTS-rereview.md
InterPro reports 0 integrated entries for Q8IPG8, and UniProt lists no PANTHER family.
file:DROME/CG31606/CG31606-deep-research-falcon.md
found no focused functional publication
GO:0005575 cellular_component
ND
GO_REF:0000015 		ACCEPT
Summary: Root cellular component ND annotation: when it was made, no cellular component had been curated for this gene product from literature.
Reason: ACCEPT under the ND acceptance rule (projects/NO_DATA.md). The evidence this review cites for the cellular component is inferred (from orthologs, family membership or sequence features) or comes from other species; none of it is literature on this gene product in this species. This was judged from the review's own content during the NO_DATA re-action pass, not from a new literature search. Earlier action: MODIFY. The term the earlier MODIFY proposed, extracellular region, is kept as its own NEW row. The gene's own literature-search record finds no study of this gene product in this species that identifies a cellular location.
Supporting Evidence:
file:DROME/CG31606/CG31606-deep-research-falcon.md
No microscopy, biochemical fractionation, proximity-labeling, organelle proteomics, secretion assay, or validated sequence-topology result was found for CG31606.
GO:0008150 biological_process
ND
GO_REF:0000015 		ACCEPT
Summary: No biological process is known. The ND root annotation is appropriate.
Reason: No perturbation or gene-specific phenotype study exists. Transcriptional responsiveness in a single high-throughput dataset, mentioned in the deep-research report, does not show that the protein takes part in any process. The gene is lineage-restricted and has no characterised relative, so no process can be inferred by homology.
Supporting Evidence:
file:DROME/CG31606/CG31606-bioinformatics/rereview/RESULTS-rereview.md
CG31606 is a taxonomically restricted gene of the *D. melanogaster* species group.
file:DROME/CG31606/CG31606-deep-research-falcon.md
found no focused functional publication
GO:0005576 extracellular region
ISM
file:DROME/CG31606/CG31606-uniprot.txt 		NEW
Summary: Inferred extracellular region for this gene product, proposed during the NO_DATA re-action pass.
Reason: Extracellular region is inferred for this gene product (ISM), not shown for it experimentally; the ND row for the aspect therefore stays (projects/NO_DATA.md). The protein has a SignalP-predicted cleavable signal peptide followed by a soluble 179-residue mature chain. It has no transmembrane segment and no C-terminal KDEL/HDEL ER-retention motif, so the default fate is secretion. The broad term GO:0005576 extracellular region is as specific as this evidence allows. A more specific location, such as extracellular space or hemolymph, would need direct localisation data. No experiment has measured where the protein is.
Supporting Evidence:
file:DROME/CG31606/CG31606-uniprot.txt
SIGNAL 1..18
file:DROME/CG31606/CG31606-bioinformatics/RESULTS.md
The C-terminal sequence is EEIASRILALKDNYQCA, without a hydrophobic anchor or canonical KDEL/HDEL retention terminus.

References

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Suggested Questions for Experts

Q: Is CG31606 secreted into the hemolymph (for example by the fat body), and does its expression respond to infection, nutrition or other stress, as for other lineage-restricted secreted Drosophila proteins?

Q: Does the weak similarity to TsetseEP-domain-labelled Drosophila proteins (for example CG42763) reflect a real shared fold?

Suggested Experiments

Experiment: Express an epitope-tagged CG31606 under its native regulatory region (or in the fat body) and test whether the protein is secreted into the hemolymph. Also check whether removing the signal peptide abolishes secretion.

Experiment: Make a CRISPR null allele and screen for viability, fertility, immune and metabolic phenotypes. Combine this with hemolymph proteomics to identify interaction partners.

Knowledge Gaps

What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).

Gap: The molecular activity, binding partners and physiological role of the secreted CG31606 protein are entirely undetermined.

OPEN BIOLOGY WHOLLY_DARK

What is known: The protein is a predicted secreted small protein with a signal peptide and no recognised domain. It is restricted to the melanogaster species group and has no characterised homolog anywhere.

What would resolve it: Localisation of a tagged protein, a loss-of-function phenotype screen and identification of interaction partners.

Provenance (the field's own admissions):

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM2 External predictions

View prediction review YAML · CG31606-protnlm-predictions-review.yaml · Review status: COMPLETE

Secretion is supported by sequence topology; lipid transport, lipid binding and lipoprotein metabolism remain unresolved.

Source documents: genes/DROME/CG31606/CG31606-predictions-source.json · genes/DROME/CG31606/CG31606-uniprot-source.json

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0006869 lipid transport GO_BP
UNC — Uncertain Review score: 1/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08 · file:DROME/CG31606/CG31606-predictions-source.json
Review rationale: Lipid transport is not established for CG31606. The raw structural donor is mammalian apolipoprotein A-V, but the strongly asymmetric TM scores do not establish target orthology or a conserved lipid-carrying mechanism. A signal peptide supports secretion rather than cargo specificity. Target lipid transport or convincing subfamily evidence is missing, and the claim is neither validated nor refuted.
Supporting Evidence:
GO:0005576 extracellular region GO_CC
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08 · file:DROME/CG31606/CG31606-predictions-source.json
Review rationale: Extracellular localization is a reasonable inference from the cleavable N-terminal signal peptide and soluble mature sequence lacking a membrane anchor or canonical ER-retention terminus. It is not an experimentally measured compartment, and the bacterial IpgD donor is not its biological justification. This broad localization is absent from the ND-only GOA record, so it is a supported novel sequence-based prediction. It does not establish extracellular-matrix residence or lipid handling.
Supporting Evidence:
GO:0008289 lipid binding GO_MF
UNC — Uncertain Review score: 1/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08 · file:DROME/CG31606/CG31606-predictions-source.json
Review rationale: No lipid-binding assay or defensible apolipoprotein subfamily placement is available for CG31606. The partial structural match to seal apolipoprotein A-V is a hypothesis lead rather than conserved ligand-binding evidence. Secretion does not identify a ligand. The exact binding claim remains unresolved.
Supporting Evidence:
GO:0042157 lipoprotein metabolic process GO_BP
UNC — Uncertain Review score: 1/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08 · file:DROME/CG31606/CG31606-predictions-source.json
Review rationale: No evidence connects CG31606 to lipoprotein metabolism. The structurally matched apolipoprotein donor is not established as an ortholog, and a predicted signal peptide does not identify a pathway. Target perturbation, biochemical context or sound comparative functional transfer is needed to evaluate this process.
Supporting Evidence:

Deep Research

Falcon

(CG31606-deep-research-falcon.md)

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📚 Additional Documentation

Notes

(CG31606-notes.md)

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Bioinformatics Results

(RESULTS.md)

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📄 View Raw YAML

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