CG42404 encodes a 1133-residue single-pass membrane protein of the DGCR2/IDD family (PANTHER PTHR15256, subfamily SF6), the insect relative of vertebrate DGCR2. Its N-terminal region carries a von Willebrand factor type C (VWFC) domain followed by a transmembrane helix, a basic juxtamembrane segment and a proline-rich PPxY-type motif, all conserved with vertebrate DGCR2, and then a long, largely disordered, low-complexity C-terminal extension that has no counterpart in vertebrate members. Unlike vertebrate DGCR2, the fly protein lacks the LDL-receptor class A module and the C-type lectin-like domain. It is expected to reside in a cellular membrane, but its topology, ligand or binding partners, molecular activity and biological role have not been determined experimentally.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: No molecular activity has been determined for CG42404; the ND placeholder is correct. Reason: A literature search found no study of this gene product beyond inclusion in wing screening tables. The domains conserved with vertebrate DGCR2 (VWFC, TM, juxtamembrane PPxY-type motif) do not by themselves specify an activity, and the fly protein lacks the C-type lectin and LDL-A modules of vertebrate DGCR2, so no candidate ligand-binding activity can be transferred. PAINT propagated no molecular function from the DGCR2 subfamily node either. Supporting Evidence: file:DROME/CG42404/CG42404-deep-research-falcon.md No retrieved study establishes its primary molecular function, catalytic activity, substrate, binding partner, pathway, or subcellular/extracellular location. file:DROME/CG42404/CG42404-bioinformatics/RESULTS-rereview.md The fly product lacks the LDL-receptor class A module and the DGCR2-type C-type lectin-like domain |
| 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. Re-checked 2026-10-31: the paper cited in core_functions (PMID:8630060) is on mammalian SEZ-12. 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/CG42404/CG42404-deep-research-falcon.md No retrieved study reports immunolocalization, fluorescent tagging, biochemical fractionation, secretion assays, or extracellular-matrix incorporation for Q9VFA8. |
| GO:0008150 biological_process | ND GO_REF:0000015 | ACCEPT | Summary: No biological process has been established for CG42404; the ND placeholder is correct. Reason: The only gene-specific data are candidate-level entries in wing gain-of-function and RNAi screen tables, which report no specific phenotype. Mouse Dgcr2 knockdown affects radial migration of cortical projection neurons and DGCR2 associates with the Reelin complex, but these are vertebrate neural functions; PAINT curators propagated only membrane from the DGCR2 subfamily node and not the vertebrate process terms, and the fly protein lacks the C-type lectin and LDL-A ectodomain modules of DGCR2. No process is transferred. Supporting Evidence: file:DROME/CG42404/CG42404-deep-research-falcon.md No 2023–2024 paper dedicated to **Q9VFA8**, **CG42404**, or **lincRNA.S6902** was retrieved. PMID:29305086 Dgcr2 knockdown impaired radial locomotion and final translocation of projection neurons, leading to persistent laminar positioning alterations. |
| GO:0016020 membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Membrane localization is supported by the PAINT node for the DGCR2 subfamily and by the conserved transmembrane helix of the fly protein. Reason: The PAINT assertion at PTN000391897 is grounded in the mouse Dgcr2 (SEZ-12) membrane annotation and covers PTHR15256:SF6, the subfamily that contains CG42404, human DGCR2 and mouse Dgcr2. The fly protein retains the DGCR2 transmembrane helix, basic juxtamembrane segment and PPxY-type motif in a block aligning at about 35% identity with DGCR2, so it is inside the clade and has kept the feature that makes the protein membrane-bound. Membrane is the only term PAINT propagated from this node, which matches the absence of any characterized activity in the family. Supporting Evidence: PMID:8630060 The deduced amino acid sequence of SEZ-12 revealed that it encodes membrane-bound C-type lectin and has a significant homology to that of human cDNA, DGCR2 and IDD file:DROME/CG42404/CG42404-uniprot.txt FT TRANSMEM 103..125 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" file:DROME/CG42404/CG42404-bioinformatics/RESULTS-rereview.md aligns fly residues 28-200 to human DGCR2 270-455 |
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Download this section (compressed HTML)Q: Is the N-terminal hydrophobic segment of CG42404 a cleaved signal peptide, making the VWFC domain extracellular and the long disordered region cytoplasmic as in vertebrate DGCR2 type I topology?
Q: Does the conserved PPPYE motif of CG42404 and DGCR2 mediate binding to WW-domain proteins, and is that interaction shared between insects and vertebrates?
Experiment: Tag endogenous CG42404 (e.g. CRISPR knock-in at the C terminus, with a separate N-terminal epitope after the putative signal peptide) to determine membrane compartment and topology in tissues where it is expressed, such as the mushroom body.
Experiment: Affinity purification with mass spectrometry from fly heads using tagged CG42404, comparing wild type with a PPPYE-to-AAAAE mutant, to identify partners that depend on the conserved motif.
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