CG10359 encodes a secreted protein of about 460-485 residues (B7Z0B2 is the longest of several isoforms) with an N-terminal signal peptide, no transmembrane segment, and a single C-terminal fibrinogen-related domain (FReD) of the kind that in other proteins forms ligand-recognition and receptor-binding surfaces. It belongs to an insect/nematode-specific subfamily of fibrinogen-domain proteins that has no experimentally characterised member. In third-instar larvae the protein is secreted from muscle, heart, wing imaginal disc and neurons into the circulating hemolymph, and an interaction-prediction analysis proposes it as a muscle-derived ligand of the integrin alpha subunit Multiple edematous wings (Mew) in imaginal discs. RNAi knockdown is lethal or semi-lethal when ubiquitous and, when neuronal, alters larval neuromuscular-junction morphology and reduces adult climbing. Its ligand, receptor and molecular activity have not been determined; it has been described both as an angiopoietin-like and as a FIBCD1-like protein on the basis of its fibrinogen domain.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001664 G protein-coupled receptor binding | ISS GO_REF:0000024 | REMOVE | Summary: Ficolin-specific GPR43 docking transferred across PANTHER subfamilies to a protein that is not a ficolin. Reason: The donor is human M-ficolin (FCN1, O00602), whose GPCR binding rests on its docking onto monocyte GPR43 (PMID:21037097), a property of a vertebrate soluble collagen-like lectin. CG10359 sits in PANTHER PTHR19143:SF327, an insect/nematode subfamily, whereas FCN1 is in SF377; CG10359 lacks the ficolin collagen-like region, and its FReD is no more similar to FCN1 than to angiopoietin-1 (about 38-39% identity). PAINT curators placed the family's signaling-receptor-binding IBD (PTN000441539) at a chordate-restricted node and did not propagate any receptor-binding function to fly members, a deliberate omission. Neither the GPCR partner nor any receptor interaction has been tested for CG10359, so this subfamily-specific function should not be transferred. Supporting Evidence: PMID:21037097 M-ficolin, a conserved soluble CL of monocyte origin, overcomes its lack of membrane-anchor domain by docking constitutively onto a monocyte transmembrane receptor, G protein-coupled receptor 43 (GPCR43) file:DROME/CG10359/CG10359-bioinformatics/RESULTS-rereview.md FCN1 (O00602) is in PTHR19143:SF377. file:DROME/CG10359/CG10359-bioinformatics/RESULTS-rereview.md FIBCD1 is no closer to CG10359 than MFAP4 or FGL1, and the ficolin FCN1 is about as distant as angiopoietin-1. file:interpro/panther/PTHR19143/PTHR19143-paint.tsv PTHR19143 PTN000441539 GO:0005102 F IBD false |
| GO:0007186 G protein-coupled receptor signaling pathway | ISS GO_REF:0000024 | REMOVE | Summary: Follows from the ficolin-GPR43 transfer, which does not apply to CG10359. Reason: This process row has the same donor and basis as the GPCR-binding row: M-ficolin signalling through GPR43 on monocytes (PMID:21037097). CG10359 is outside the ficolin subfamily, no GPCR partner is known, and the only receptor proposed for it from fly data is the integrin alpha subunit Mew (PMID:42009678), not a GPCR. A 2014 study that considered CG10359 as a possible angiopoietin-like Tie ligand found a negative deficiency result (PMID:24675716). There is no basis for GPCR pathway participation. Supporting Evidence: PMID:21037097 the M-ficolin-GPCR43 complex activates the NF-ΞΊB cascade to upregulate IL-8 production PMID:42009678 candidate inter-organ ligands, including muscle-secreted CG10359 binding to Multiple edematous wings (Mew) in imaginal discs PMID:24675716 The results with Pvf2 and CG10359 were negative (not shown) |
| GO:0008061 chitin binding | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: FIBCD1 chitin binding is transferred across PANTHER subfamilies; untested for CG10359. Reason: The donor, human FIBCD1, binds chitin and acetylated compounds through its fibrinogen domain (PMID:19710473). CG10359 was called a potential FIBCD1 orthologue on the basis of FReD similarity (PMID:35916241), but PANTHER places FIBCD1 in vertebrate-only SF45 and CG10359 in insect/nematode SF327, and the CG10359 FReD is about as similar to FIBCD1 (41%) as to MFAP4 or FGL1, and closer still to its own fly paralogs. The acetyl-binding pocket has not been examined and no binding assay has been done on CG10359; the fly paper assayed GAG binding only for vertebrate FIBCD1. Chitin is abundant in insects, so the activity is plausible, but it rests only on a cross-subfamily domain transfer. Supporting Evidence: PMID:19710473 Functional analysis showed a high-affinity and calcium-dependent binding of acetylated components to the fibrinogen domain PMID:35916241 we identified the D. melanogaster gene CG10359 as a potential orthologue of FIBCD1 file:DROME/CG10359/CG10359-bioinformatics/RESULTS-rereview.md Human FIBCD1 (Q8N539) is in PTHR19143:SF45 (vertebrate members only) file:DROME/CG10359/CG10359-bioinformatics/RESULTS-rereview.md The analysis does not test whether CG10359 binds acetylated ligands; binding-pocket residues were not examined. |
| GO:0016020 membrane | ISS GO_REF:0000024 | REMOVE | Summary: The donor's membrane location comes from a transmembrane anchor that CG10359 lacks. Reason: FIBCD1 is a type II transmembrane receptor (PMID:19710473, PMID:35916241), so its membrane location is a consequence of its N-terminal transmembrane segment. No CG10359 isoform has a transmembrane segment; all have a cleavable signal peptide, and the protein is secreted from several larval tissues into the hemolymph (PMID:42009678). Transferring a membrane location from a transmembrane donor to a soluble secreted protein is not supported, and no membrane association of CG10359 has been reported. Supporting Evidence: PMID:19710473 novel homotetrameric 55-kDa type II transmembrane protein encoded by the FIBCD1 gene PMID:35916241 FIBCD1 is a type 2 receptor with high homology to ficolins and consists of a short Nβterminal cytoplasmic tail, transmembrane domain file:DROME/CG10359/CG10359-uniprot.txt FT SIGNAL 1..23 FT /evidence="ECO:0000256|SAM:SignalP" file:DROME/CG10359/CG10359-bioinformatics/RESULTS-rereview.md None carries a predicted transmembrane segment. PMID:42009678 We removed B7Z0B3 (CG10359) from muscle, because B7Z0B2 (CG10359) was identified from muscle/heart/wingdisc/neurons. |
| GO:0031012 extracellular matrix | IBA GO_REF:0000033 | MODIFY | Summary: Root-node matrix localization is broader in scope than the evidence for this secreted protein; generalize to extracellular region. Reason: The row descends from PTN000441162, the PTHR19143 root node, where PAINT placed extracellular-matrix localization on the basis of vertebrate matrix proteins (MFAP4, tenascins and related donors). CG10359 is inside the family, carries a signal peptide and is secreted, so an extracellular location is well supported by its own evidence: it is among the high-confidence tissue-secreted hemolymph proteins of larvae (PMID:42009678). The family also contains soluble serum lectins and circulating hormone-like proteins, and nothing shows that CG10359 is retained in a matrix rather than circulating. The supported claim is extracellular location; matrix residence is not refuted but is not established for this subfamily. GO:0005576 extracellular region keeps the extracellular placement without asserting matrix retention. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000441162 SUPPORTS SOURCE BUT NOT TARGET The root IBD rests on vertebrate matrix-protein donors; for the CG10359 subfamily only secretion into the extracellular space (hemolymph) is supported. Proposed replacements: extracellular region Supporting Evidence: file:interpro/panther/PTHR19143/PTHR19143-paint.tsv PTHR19143 PTN000441162 GO:0031012 C IBD false MGI:MGI:2665790|MGI:MGI:99516|RGD:3886|UniProtKB:P55083|UniProtKB:P55918|UniProtKB:Q9UQP3 taxon: 20260529 PMID:42009678 We removed B7Z0B3 (CG10359) from muscle, because B7Z0B2 (CG10359) was identified from muscle/heart/wingdisc/neurons. file:DROME/CG10359/CG10359-uniprot.txt FT SIGNAL 1..23 FT /evidence="ECO:0000256|SAM:SignalP" file:DROME/CG10359/CG10359-uniprot.txt FT DOMAIN 263..477 FT /note="Fibrinogen C-terminal" FT /evidence="ECO:0000259|PROSITE:PS51406" |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Does the CG10359 fibrinogen-related domain retain the acetyl-group binding pocket and calcium site that FIBCD1 and ficolins use for ligand recognition, or has the insect SF327 subfamily diverged in ligand specificity?
Q: Is the predicted muscle-secreted CG10359 to imaginal-disc Mew interaction a direct physical binding, and does CG10359 act as an integrin ligand?
Experiment: Express the CG10359 FReD (shared by all isoforms) and test binding to chitin, chitin oligomers, acetylated BSA and glycosaminoglycans, with FIBCD1 FReD as a positive control.
Experiment: Test direct binding of CG10359 to the Mew (alphaPS1) integrin ectodomain and, in vivo, whether muscle-specific CG10359 knockdown phenocopies or modifies mew loss in imaginal discs.
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The molecular activity of CG10359 is unknown: no ligand of its fibrinogen-related domain and no receptor has been shown, and no member of its PANTHER subfamily (SF327) has been characterised.
BIOLOGY MF_DARK
What is known: Established are secretion into larval hemolymph from several tissues, a FReD without a transmembrane anchor, and neuronal RNAi phenotypes at the neuromuscular junction. The proposed Mew interaction is a computational ligand-receptor prediction.
Significance: Determines whether CG10359 is a lectin-like recognition protein (as FIBCD1 and ficolins are), an integrin ligand, or a growth-factor-like signal, and therefore which, if any, homology-based annotations apply.
What would resolve it: Binding assays of recombinant CG10359 FReD with acetylated glycans/chitin and with the Mew ectodomain, and tests of whether neuronal or muscle-specific loss alters Mew-dependent imaginal disc or neuromuscular-junction phenotypes.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)