The selected accession is the native 464 aa PF isoform (FlyBase FBpp0309562), not PD. Sequence analysis verifies one lysine difference relative to 465 aa PB and retention of all three DRBM domains. No wrong-input claim is warranted.
PMID:17666393(https://pubmed.ncbi.nlm.nih.gov/17666393/) explicitly assigns pre-miRNA binding to DRBM2 and Dcr-1 binding to DRBM3. This justifies PB-to-PF transfer for the broad core activity. PMID:19635780(https://pubmed.ncbi.nlm.nih.gov/19635780/) resolves the distinct PD siRNA role, so gene-level siRNA annotations remain UNDECIDED for exact PF rather than being removed. Germline/CNS phenotypes are retained as non-core, with experimental isoform limits explicit.
The broad prediction is LSP; the accompanying mammalian complex narrative needs pathway-specific correction. Raw predictions and source metadata are preserved. Missing fulltext flags are set from publication caches; the abstract-only papers explicitly support the quoted gene-level claims without inventing unobserved assay details.
Falcon completed and was read. It distinguishes PB and PD and identified PMID:17928574(https://pubmed.ncbi.nlm.nih.gov/17928574/) on Loqs dispensability for miRISC assembly; this publication was fetched and inspected directly. Its unresolved PF identity is addressed by the local sequence comparison. The narrative separates complex association from an obligatory RISC-assembly role. The advisory about no direct Falcon citation is accepted because consequential claims cite the underlying sources.
Scope: every existing annotation, the description and core functions re-examined against the cached literature, the Swiss-Prot canonical entry Q9VJY9 (loqs-reference-Q9VJY9-uniprot.txt) and PANTHER placement. No ProtNLM2 file was opened or used.
Identity of the benchmark accession. X2J5X6 is UniProt "Loquacious, isoform F" (TrEMBL, 464 aa), an alternative splice product of loqs, not the canonical product. The canonical Swiss-Prot entry is Q9VJY9 (465 aa, isoform PB displayed; PA, PC, PD as named isoforms). New script loqs-bioinformatics/compare_sequences_rereview.py (output results/rereview.json, summary RESULTS-rereview.md) shows that PF = PB minus a single residue, Lys384. This corrects the earlier RESULTS.md, which put it at 383 (Gln383 is retained). Position 384 is the first residue after the PA/PC-variable segment 338..383, so the deletion sits at an exon junction. It lies two residues after the LLKL 379..382 motif (mutation strongly reduces Dcr-1 activity, PMID:26769856) and inside the linker that the same paper reports "contributes significantly to dmDcr1 binding". All three DRBMs, the pre-miRNA-binding residues 308..309 and the Dcr-1-binding C-terminus are intact, so no catalytic or binding residue is missing. Effects of the missing lysine have not been measured. PF function is inferred from PB.
Evolutionary grounding. PANTHER PTHR46205 (official name "LOQUACIOUS, ISOFORM B"): loqs is in SF3 with C. elegans rde-4. Mammalian TARBP2 is SF1 and PRKRA SF2; fly r2d2 is SF4 and blanks/DIP1 are SF5. Mammalian TRBP-specific features (DICER1/TARBP2/AGO2 RLC composition) were therefore not transferred. GOA has no IBA rows for this accession. All function claims rest on fly experiments with PB (and PD for siRNA), transferred to PF by sequence identity to PB, the same gene and the same exons.
Changes vs previous review:
- GO:0005515 protein binding (IPI, Dcr-1): KEEP_AS_NON_CORE → MODIFY to GO:0170054 ribonuclease activator activity (Loqs-PB binds Dcr-1 and increases its pre-miRNA affinity and miRNA output; PMID:17666393, PMID:15985611, PMID:15918769). This complies with the GO:0005515 policy. GO:0170054 also becomes the second core function, in the RISC-loading complex.
- GO:0010468 regulation of gene expression (IEA): ACCEPT → MODIFY to GO:0031054. OLS4 ancestors confirm that pre-miRNA processing is a descendant of regulation of gene expression via regulatory ncRNA-mediated gene silencing.
- GO:0009047 dosage compensation (IGI, PMID:22554892): UNDECIDED → MARK_AS_OVER_ANNOTATED. In the full text, the evidence is reduced survival of roX1 roX2 males carrying loqs f00791, an allele that removes all isoforms. This is a sensitized-viability necessity result that identifies no step Loqs performs. The siRNA connection, if any, would be PD.
- RISC-loading complex: kept ACCEPT, now noting PMID:17928574 (loqs-null flies still assemble miRISC). Membership is supported by co-purification (PMID:15918769) and the curated Q9VJY9 miRLC statement. No RISC-assembly process is asserted.
- siRNA processing (×3) and regulation of regulatory ncRNA processing: kept UNDECIDED, with clearer reasons. The experiments are sound at gene level, and the PMID:21419681 IDA measures Loqs-PD lowering the KM of Dcr-2. PF is PB-like, and the PB-vs-PD split (PMID:19644447, PMID:19635780) means these rows are neither confirmed nor refuted for this product.
- Unchanged: dsRNA binding ACCEPT; RNA binding and miRNA metabolic process MODIFY; pre-miRNA processing ×4 ACCEPT; cytoplasm ACCEPT; CNS development, GSC maintenance, GSC asymmetric division and oogenesis KEEP_AS_NON_CORE (downstream miRNA-dependent requirements).
- Description rewritten as a gene-level summary covering the isoform split. Added references PMID:26769856, PMID:17928574 and the Q9VJY9 flat file. Old RESULTS.md reference kept, with a note on the off-by-one.
Relative to review next. The canonical product of the same gene, Q9VJY9 (Loqs, isoform PB; Swiss-Prot), has no review in the repo (grep Q9VJY9 genes/*/*/*-ai-review.yaml finds nothing). Because genes/DROME/loqs is keyed to the isoform-F accession, the canonical review would go in genes/DROME/loqs__Q9VJY9.
Family review / modules. interpro/panther/PTHR46205/PTHR46205-review.yaml puts loqs (X2J5X6) in SF3, which agrees with UniProt and PANTHER 19.0. There is no disagreement on subfamily placement. Its only representative is the isoform accession; adding the canonical Q9VJY9 would be better. Module: modules/dmel_risc_loading_complexes.yaml (miRLC part uses UniProtKB:Q9VJY9; it notes PB/PD isoform specificity). No GO-CAM index entry was found for Q9VJY9 or X2J5X6.