CG14662 encodes an uncharacterized 550-residue membrane protein with an extracellular (or luminal) leucine-rich-repeat region. Two hydrophobic segments are predicted (residues 29-50 and 421-447). The first lies after a positively charged 28-residue N-terminus, so it may act as an uncleaved signal anchor, although a comparative survey of extracellular LRR proteins called it a signal sequence. Either way, the region between the two segments faces the outside of the cell or the lumen. It carries all seven N-glycosylation sequons, an LRR-superfamily domain of about six degenerate repeats, a Ser/Thr-rich disordered stretch that could form a mucin-like stalk, and a cysteine-rich segment next to the membrane. The roughly 100-residue cytoplasmic tail has no recognisable signalling domain. The protein has no TIR domain and is not a Toll-family receptor. Its orthologs occur only in higher flies (Brachycera), and none has been characterized. No ligand, binding partner, expression-based role or loss-of-function phenotype has been reported. The protein most likely mediates extracellular recognition or adhesion, as many single-pass LRR proteins do, but this remains a hypothesis based on its domains.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: No molecular activity has been demonstrated, so the ND placeholder is correct. Reason: Dedicated literature searches found only an architectural catalogue entry (Dolan et al. 2007) and a passing mention near a GWAS locus. The LRR-superfamily region suggests some protein or ligand interaction, but it does not identify a specific activity. The lineage-restricted orthogroup contains no characterized member from which an activity could be inherited. The weak InterPro match to PANTHER PTHR24365:SF541 (Toll-related) is not part of PANTHER's own classification of this protein. It also covers no TIR domain, so it gives no basis for transferring signaling receptor activity. The ND statement therefore holds. Supporting Evidence: file:DROME/CG14662/CG14662-deep-research-falcon.md No direct experimental functional characterization or substantive 2023β2024 update was found. PMID:17868438 CG14662550SS, 6LRR, TM file:DROME/CG14662/CG14662-bioinformatics/RESULTS-rereview.md No catalytic domain, TIR domain or other signalling domain is present. |
| 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, membrane, 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/CG14662/CG14662-deep-research-falcon.md No gene-specific microscopy, biochemical fractionation, surface labeling, or topology experiment was found. |
| GO:0008150 biological_process | ND GO_REF:0000015 | ACCEPT | Summary: No biological process is established, so the ND placeholder is correct. Reason: No loss-of-function, expression-pattern or interaction study links CG14662 to a process. A 2024 dissertation mentions the gene only because it lies near the CG2022 GWAS locus, which is not evidence of involvement. A single-pass LRR architecture is shared by proteins in immunity, neural wiring, adhesion and development, so it cannot select among these processes. The weak Toll-related PANTHER HMM match does not justify a Toll-signaling assignment. Supporting Evidence: file:DROME/CG14662/CG14662-deep-research-falcon.md No direct experimental functional characterization or substantive 2023β2024 update was found. PMID:17868438 These are genes with no recognizable orthologue in the other species (fly or mouse) and no recognizable paralogue in their own species. |
| GO:0016020 membrane | ISM file:DROME/CG14662/CG14662-uniprot.txt | NEW | Summary: Inferred membrane for this gene product, proposed during the NO_DATA re-action pass. Reason: Membrane is inferred for this gene product (ISM), not shown for it experimentally; the ND row for the aspect therefore stays (projects/NO_DATA.md). Phobius places helical transmembrane segments at 29-50 and 421-447, and an independent Kyte-Doolittle scan recovers both. The intervening region carries all seven N-glycosylation sequons, which fits a type-I or N-in two-pass integral membrane protein. GO:0016020 membrane is therefore the most specific location the evidence supports. The protein most likely ends up in the plasma membrane, but no localization experiment exists, and a membrane protein with YxxΦ motifs in its tail could equally reside in endosomes. Plasma membrane is therefore not asserted. Supporting Evidence: file:DROME/CG14662/CG14662-uniprot.txt FT TRANSMEM 29..50 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" file:DROME/CG14662/CG14662-uniprot.txt FT TRANSMEM 421..447 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" file:DROME/CG14662/CG14662-bioinformatics/RESULTS-rereview.md The luminal/extracellular segment carries all seven N-glycosylation sequons (64-391), consistent with that orientation; none is in the C-terminal tail. PMID:17868438 CG14662550SS, 6LRR, TM |
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Download this section (compressed HTML)Q: Is the first hydrophobic segment (29-50) a cleaved signal peptide or an uncleaved signal anchor? The answer decides whether CG14662 is a single-pass or a two-pass (N-in, C-in) membrane protein.
Q: Does the extracellular LRR/Ser-Thr/Cys-rich region bind a partner on neighbouring cells, as in other single-pass LRR adhesion or guidance proteins? Or does it bind a soluble ligand?
Q: Is the PANTHER PTHR24365:SF541 (Toll-related) HMM match reported by InterPro meaningful for a protein without a TIR domain, or is it a spurious match driven by the LRR region?
Experiment: Tag the endogenous protein at its C terminus by CRISPR knock-in. Determine its tissue and subcellular distribution, and use antibody access to an extracellular epitope tag together with PNGase F sensitivity to test topology and N-glycosylation.
Experiment: Generate a CRISPR null allele and screen viability, fertility, nervous-system and immune phenotypes. Perform affinity purification or a cell-surface interaction screen with the purified extracellular region to identify binding partners.
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The molecular activity, ligands or binding partners, membrane topology and physiological role of CG14662 are all unknown.
OPEN BIOLOGY WHOLLY_DARK
What is known: Sequence analysis predicts a membrane protein with a glycosylated extracellular LRR region, a Ser/Thr-rich stalk, a cysteine-rich juxtamembrane segment and a cytoplasmic tail without a known signalling domain. Orthologs exist only in Brachycera, and none is characterized.
What would resolve it: Endogenous tagging to determine localization and topology, extracellular-domain interaction screens and a null-allele phenotype screen.
Provenance (the field's own admissions):
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