LOC117183218

UniProt ID: A0A6I8W8A2
Organism: Drosophila pseudoobscura pseudoobscura
Review Status: DRAFT
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Gene Description

Uncharacterized short RCC1-repeat protein encoded by LOC117183218 on the X chromosome of Drosophila pseudoobscura. This entry is RefSeq isoform X3 (XP_033239512.1, 169 aa); the gene's longest product is isoform X1 (A0A6I8W805, 282 aa), and residues 6-169 of X3 are identical to residues 119-282 of X1, so X3 differs only by an alternative five-residue N-terminus and the absence of the first 118 residues of X1. X3 carries two RCC1 repeats that fold as part of an RCC1-like beta-propeller. No product of the gene has a HECT domain or any other catalytic module. The RefSeq name "probable E3 ubiquitin-protein ligase HERC3" reflects similarity of the RCC1 repeats only. The sequence is most similar (about 76-79% identity over ~215 residues) to the N-terminal RCC1-like domain of D. pseudoobscura Herc4, and less similar to D. melanogaster Herc4. Together with a paralogous RCC1-only gene (LOC6903915), this suggests the gene arose by partial duplication of the Herc4 RCC1-like domain within the obscura lineage; NCBI lists no orthologs. No molecular function, interaction partner, localization or expression has been reported. RCC1-like propellers commonly act as protein-binding or small-GTPase-regulatory platforms, but neither role has been tested for this protein.

Core Functions

No molecular function is established. The product is an isolated RCC1-repeat (RCC1-like beta-propeller) segment that lacks the HECT ubiquitin-ligase domain of Herc4, the HECT-containing protein from which it appears to derive. Ubiquitin-protein ligase activity, ERAD and other HERC3/HERC4 functions therefore cannot be transferred. Whether the protein binds the substrates or partners of the Herc4 RCC1-like domain, or acts as a competitor of Herc4, is unknown.

Supporting Evidence:
  • file:DROPS/A0A6I8W8A2/A0A6I8W8A2-uniprot.txt
    FT REPEAT 88..142
  • file:DROPS/A0A6I8W8A2/A0A6I8W8A2-bioinformatics/RESULTS.md
    No product of the gene has a HECT domain (the longest is 282 aa; a HECT domain alone is ~350 aa).
  • file:DROPS/A0A6I8W8A2/A0A6I8W8A2-bioinformatics/RESULTS.md
    Higher identity to D. pseudoobscura Herc4 than to D. melanogaster Herc4 indicates that LOC117183218 (and LOC6903915) arose by partial duplication of the Herc4 RCC1-like-domain region within the obscura lineage.

References

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Suggested Questions for Experts

Q: Is LOC117183218 a lineage-specific partial duplicate of the Herc4 RCC1-like domain in the obscura group, and is it present in close relatives such as D. persimilis and D. miranda?

Q: Is any LOC117183218 isoform translated, and is the X3 alternative N-terminus (MSPLI) supported by transcript evidence?

Q: Should PANTHER place all isoforms of this gene in one family? Isoform X2 (A0A6I8W807) is assigned to PTHR22870:SF408 while X1, X3 and X4 are in PTHR22872 without a subfamily.

Suggested Experiments

Experiment: RNA-seq and ribosome-profiling or proteomic analysis of D. pseudoobscura tissues to test whether LOC117183218 isoforms are transcribed and translated.

Hypothesis: LOC117183218 is expressed as an RCC1-only protein rather than being a non-coding or untranslated duplicate.

Experiment: Phylogenetic analysis of Herc4 RCC1-like domains together with LOC117183218 and LOC6903915 across Drosophila species, combined with synteny, to date the duplication.

Hypothesis: LOC117183218 arose from partial duplication of Herc4 within the obscura lineage.

Experiment: Co-immunoprecipitation of tagged LOC117183218 isoforms from fly cells, followed by mass spectrometry, compared with the Herc4 RCC1-like domain.

Hypothesis: The RCC1-only product binds partners of the Herc4 RCC1-like domain and could compete with Herc4.

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· A0A6I8W8A2-protnlm-predictions-review.yaml Β· Review status: COMPLETE

The 169-residue RCC1-like sequence (LOC117183218 isoform X3) does not contain a ligase catalytic module, and no product of the gene has a HECT domain.

Source documents: genes/DROPS/A0A6I8W8A2/A0A6I8W8A2-uniprot.txt Β· genes/DROPS/A0A6I8W8A2/A0A6I8W8A2-goa.tsv Β· genes/DROPS/A0A6I8W8A2/A0A6I8W8A2-hypotheses/prediction-ligase-activity/openscientist.md

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

GO:0016874 ligase activity GO_MF
NPI β€” Nonparalog incorrect Review score: 0/2
Prediction method: ProtNLM2 Β· Version: UniProt 2024_06 pilot
DOMAIN ARCHITECTURE MISMATCH
Review rationale: The deposited sequence is a short RCC1-repeat protein with RCC1/BLIP-II fold assignments and no HECT or other ligase catalytic module. An RCC1 region from a larger HERC-like protein does not carry the catalytic activity of that protein's separate HECT domain. The prediction of intrinsic ligase activity is therefore incompatible with the available domain architecture. Sequence comparison of all products of LOC117183218 (the longest is 282 aa) finds no HECT domain in any of them, so the refutation holds at the gene level; the gene has no GO annotations, and the gene review records no established molecular function.
Supporting Evidence:

Deep Research

Falcon

(A0A6I8W8A2-deep-research-falcon.md)

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OpenScientist

(A0A6I8W8A2-hypotheses/prediction-ligase-activity/openscientist.md)

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πŸ“š Additional Documentation

Notes

(A0A6I8W8A2-notes.md)

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Bioinformatics Results

(RESULTS.md)

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πŸ“„ View Raw YAML

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