LOC117183218

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

Uncharacterized 169-amino-acid protein from Drosophila pseudoobscura pseudoobscura, annotated by RefSeq as a probable E3 ubiquitin-protein ligase HERC3 isoform X3 (XP_033239512.1). The protein contains two RCC1 (Regulator of Chromosome Condensation 1) repeats (positions 32-87 and 88-142) but entirely lacks the C-terminal HECT catalytic domain that is required for ubiquitin-protein ligase activity in HERC family proteins. Full-length HERC3 orthologs (~120 kDa) possess both an N-terminal RCC1-like domain (RLD) for substrate recognition and a C-terminal HECT domain (~350 amino acids) for catalytic ubiquitin transfer; this short isoform retains only the former. The RCC1-like domain in HERC proteins functions as a protein-protein interaction module mediating substrate recognition, distinct from canonical RCC1 which acts as a guanine nucleotide exchange factor for the Ran GTPase. This protein belongs to the PANTHER family PTHR22872 (Diverse Signaling and Regulatory Domain-Containing Protein). It is unreviewed in UniProt (TrEMBL) with evidence level PE 4 (predicted), has no curated GO annotations, and may represent a computationally predicted truncated splice variant rather than a biologically functional gene product.

Core Functions

The RCC1-like domain (RLD) in this protein fragment is predicted to mediate protein-protein interactions based on domain architecture conservation with mammalian HERC3 orthologs. In full-length HERC3, the RLD serves as a substrate-recognition module that binds target proteins and directs them for ubiquitination by the HECT domain. However, this 169 AA isoform X3 lacks the HECT catalytic domain entirely and therefore cannot independently catalyze ubiquitin ligation. Whether this truncated form has biological function independent of the full-length HERC3 protein remains unknown.

Molecular Function:
molecular_function
Cellular Locations:
cytoplasm
Supporting Evidence:
  • file:DROPS/A0A6I8W8A2/A0A6I8W8A2-deep-research-falcon.md
    RCC1-like domain mediates substrate recognition and protein-protein interactions in HERC3 orthologs
  • file:DROPS/A0A6I8W8A2/A0A6I8W8A2-protnlm-predictions-review.yaml
    This 169 AA protein is far too short to contain a HECT domain (typically 350+ AA) and its entire domain architecture consists exclusively of two RCC1 repeats

References

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Suggested Questions for Experts

Q: Is this predicted isoform X3 (LOC117183218) actually expressed as an mRNA or protein in Drosophila pseudoobscura, or is it a gene prediction artifact?

Q: If expressed, does the isolated RCC1-like domain fragment retain any protein-protein interaction capability independent of the full-length HERC3?

Q: What is the full-length HERC3 ortholog in D. pseudoobscura, and does it contain the complete domain architecture (RLD + HECT) expected for E3 ubiquitin-protein ligase activity?

Suggested Experiments

Experiment: RT-PCR or RNA-seq analysis to confirm whether this predicted isoform X3 transcript is expressed in D. pseudoobscura tissues

Hypothesis: The predicted isoform X3 transcript may not be expressed and could represent a gene prediction artifact

Experiment: If expressed, pull-down or co-immunoprecipitation experiments to test whether the isolated RCC1 repeat fragment retains protein binding capability

Hypothesis: The isolated RCC1-like domain may retain substrate recognition capability even without the HECT catalytic domain

Experiment: Comparative genomics to determine whether the full-length HERC3 locus in D. pseudoobscura encodes a complete HECT domain in other predicted isoforms

Hypothesis: A full-length HERC3 ortholog with complete domain architecture exists at this locus in D. pseudoobscura

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

The 169-residue RCC1-like sequence does not contain a ligase catalytic module.

Source documents: genes/DROPS/A0A6I8W8A2/A0A6I8W8A2-uniprot.txt · genes/DROPS/A0A6I8W8A2/A0A6I8W8A2-goa.tsv · 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 — Nonparalog incorrect Review score: 0/2
Prediction method: ProtNLM2 · 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. This assessment concerns the deposited sequence; it does not establish whether a longer gene model at the locus encodes a ligase.
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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