CG31099

UniProt ID: Q8IMT2
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

CG31099 (also catalogued as Dro14-0 and, in some records, CG10551) encodes a 400-residue member of the insect ecdysteroid kinase-like (EcKL) family. The protein consists of a single CHK kinase-like (APH-type) domain that retains the HxDxxxxN catalytic-loop motif typical of small-molecule kinases of this fold, and it belongs to PANTHER subfamily PTHR11012:SF6 together with CG6830. EcKL proteins are proposed to transfer phosphate from ATP to hydroxyl groups on small molecules such as ecdysteroids or dietary and environmental toxins, but no substrate, enzymatic activity, subcellular location or pathway has been experimentally established for CG31099. The two biochemically characterized ecdysteroid 22-kinases of the family (silkworm BmEc22K and mosquito AgEcK2) lie in other subfamilies. Ubiquitous RNAi knockdown reduced adult offspring numbers in a family-wide screen, suggesting a developmental requirement whose molecular basis is unknown.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0106389 ecdysteroid 22-kinase activity
TAS
PMID:32540344
Genomic and transcriptomic analyses in Drosophila suggest th...
UNDECIDED
Summary: FlyBase TAS for ecdysteroid 22-kinase activity, traced to the 2020 Drosophila EcKL family analysis. The accessible abstract frames the family as candidate detoxification kinases and does not report a CG31099 assay; the full text could not be read. Phylogenetically, CG31099 is not in the subfamily of either characterized ecdysteroid 22-kinase.
Reason: The supporting publication is abstract-only in our cache and the bioRxiv/journal full text was not retrievable, so the specific author statement the FlyBase curator relied on cannot be read; per the curation rules this TAS is left UNDECIDED rather than removed. The available evidence leans against a confident transfer of this precise activity. (1) The cited abstract proposes a family-wide detoxification-kinase hypothesis, not a demonstrated ecdysteroid C-22 phosphorylation by CG31099. (2) The 2024 phylogenomic study places the only two genes known to encode ecdysteroid 22-kinases (BmEc22K, subfamily A; AgEcK2, subfamily D) in different EcKL subfamilies and names its Drosophila ecdysteroid-kinase candidates as CG5644, CG13813 and Pinkman, not CG31099. (3) In PANTHER, CG31099 is in PTHR11012:SF6, whereas BmEc22K (Q0PCR8) is in SF54 and CG5644, the direct ortholog of AgEcK2, is in SF47 (file:DROME/CG31099/CG31099-bioinformatics/RESULTS-rereview.md); the only other fly SF6 member, CG6830, is uncharacterized. There are no IBA annotations from PAINT for this subfamily. The CHK domain retains its HxDxxxxN catalytic-loop motif, so a small-molecule kinase activity is plausible, but neither the substrate class nor the C-22 regiospecificity is supported by evolutionary placement or by any target-specific experiment.
Supporting Evidence:
PMID:32540344
We propose the hypothesis that members of the arthropod-specific ecdysteroid kinase-like (EcKL) gene family encode detoxicative kinases.
file:DROME/CG31099/CG31099-uniprot.txt
/note="CHK kinase-like"
PMID:38291829
Our results show the only two genes known to encode ecdysteroid kinases belong to different subfamilies and therefore ecdysteroid metabolism functions must be spread throughout the EcKL family.
PMID:38291829
CG13813 and Pinkman are D. melanogaster subfamily A genes that could also encode ecdysteroid kinases
file:DROME/CG31099/CG31099-bioinformatics/RESULTS-rereview.md
neither biochemically characterised ecdysteroid 22-kinase

References

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Suggested Questions for Experts

Q: Does the full text of PMID:32540344 (or its bioRxiv preprint) contain a CG31099-specific statement that FlyBase used for the ecdysteroid 22-kinase TAS, or was the annotation made by analogy to BmEc22K for the whole EcKL family?

Q: Where does PANTHER subfamily PTHR11012:SF6 (CG31099, CG6830) fall among the 13 EcKL subfamilies of Scanlan and Robin (2024), and does any characterized EcKL lie in that subfamily?

Suggested Experiments

Experiment: Express recombinant CG31099 and screen ATP-dependent phosphorylation of ecdysone, 20-hydroxyecdysone and a panel of hydroxylated xenobiotics by LC-MS product identification, alongside a catalytic-loop (H248/D250/N255) mutant control.

Type: in vitro enzyme assay

Experiment: Generate a CRISPR null allele of CG31099, confirm the RNAi developmental phenotype with genomic rescue, and compare ecdysteroid-phosphate conjugate profiles between null and control animals.

Type: genetic loss of function with metabolomics

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 Β· CG31099-protnlm-predictions-review.yaml Β· Review status: COMPLETE

Phosphorylation is plausible for this EcKL/CHK-kinase-like protein, but the available family study proposes rather than demonstrates the relevant reactions across this diverse family.

Source documents: genes/DROME/CG31099/CG31099-predictions-source.json Β· genes/DROME/CG31099/CG31099-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:0016310 phosphorylation GO_BP
UNC β€” Uncertain Review score: 1/2
Prediction method: ProtNLM2 Β· Version: UniProt API snapshot 2026-09-08 Β· file:DROME/CG31099/CG31099-predictions-source.json
Review rationale: Phosphorylation is plausible for this EcKL/CHK-kinase-like protein, but the available family study proposes rather than demonstrates the relevant reactions across this diverse family. No CG31099 substrate, product or catalytic assay is established in the accessible evidence, and the existing ecdysteroid 22-kinase TAS annotation is itself unresolved. Domain nomenclature and agreement with that annotation therefore cannot independently validate the process, although there is no evidence refuting it. CG31099 lies in PANTHER subfamily PTHR11012:SF6 with only the uncharacterized CG6830, outside the subfamilies of both characterized ecdysteroid 22-kinases, so no phylogenetic transfer supports it. The term would be novel relative to GOA, which carries no process annotation for this gene and whose ecdysteroid 22-kinase activity term does not entail phosphorylation by is_a or part_of.
Supporting Evidence:
  • PMID:32540344: "We propose the hypothesis that members of the arthropod-specific ecdysteroid kinase-like (EcKL) gene family encode detoxicative kinases."
  • file:DROME/CG31099/CG31099-uniprot.txt: "/note="CHK kinase-like""
  • PMID:38291829: "Our results show the only two genes known to encode ecdysteroid kinases belong to different subfamilies and therefore ecdysteroid metabolism functions must be spread throughout the EcKL family."

Deep Research

Falcon

(CG31099-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(CG31099-notes.md)

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πŸ“„ View Raw YAML

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