CG17404 (SP149) encodes a 275-residue secreted serine protease of the chymotrypsin (S1A) family. It has an N-terminal signal peptide (residues 1-20), a short 14-residue propeptide and a single trypsin-like S1 catalytic domain (residues 35-274). It has no clip domain or other accessory module. The His80-Asp124-Ser225 catalytic triad and the GDSGG oxyanion/nucleophile motif are intact, so the protein is predicted to be a catalytically active serine endopeptidase. It is probably made as a zymogen and activated by cleavage at the R34-I35 bond, which would release the IVGG mature N terminus. In the PANTHER tree CG17404 belongs to a small subfamily (PTHR24256:SF562). The subfamily contains two tandem Drosophila paralogs (CG12256 and CG3916) and single-copy genes from mosquito, beetle and Trichoplax, but no characterised member. Its substrate, cleavage specificity, tissue of action and physiological role are unknown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004252 serine-type endopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Serine-type endopeptidase activity inherited from the PTN001207268 root node is supported by an intact catalytic triad. Reason: PAINT placed the GO:0004252 IBD at PTN001207268, the Eumetazoa-level duplication node of PTHR24256 from which the SF562 clade containing CG17404 branches directly. The curator withdrew the term (NOT, IKR) from several serine-protease-homolog branches whose catalytic residues are lost, but none of these negated nodes lies on the Q9VGC0 lineage. The target retains His80, Asp124 and Ser225 in canonical motifs, so the inherited activity is not contradicted. Substrate specificity is not inferred. Supporting Evidence: file:DROME/CG17404/CG17404-uniprot.txt DR PANTHER; PTHR24256; TRYPTASE-RELATED; 1. file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md The SF562 clade branches directly from PTN001207268, the Eumetazoa-level duplication node that also carries the PAINT IBD assertions for GO:0004252, GO:0006508 and GO:0005576 that Q9VGC0 inherits. file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md None lies on the Q9VGC0 lineage. file:DROME/CG17404/CG17404-uniprot.txt DR InterPro; IPR001314; Peptidase_S1A. file:DROME/CG17404/CG17404-uniprot.txt DR Pfam; PF00089; Trypsin; 1. file:DROME/CG17404/CG17404-uniprot.txt DR PROSITE; PS00134; TRYPSIN_HIS; 1. file:DROME/CG17404/CG17404-uniprot.txt DR PROSITE; PS00135; TRYPSIN_SER; 1. file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md The three PROSITE-ProRule active-site positions carry the catalytic residues of an S1A serine protease: His80 (context ILTAAHCCQGL), Asp124 (context ELVTSDLAVLS) and Ser225 (context ACSGDSGGPLV). PMID:30367934 SPs or SPHs based on the presence or absence of the His-Asp-Ser catalytic triad |
| GO:0004252 serine-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Serine-type endopeptidase activity is correct at this level of specificity. Reason: This combined-IEA row draws on the trypsin-domain and TRYPSIN_HIS InterPro signatures and the PROSITE-derived EC 3.4.21.1 (chymotrypsin) rule. The GO term asserted is the general serine-type endopeptidase activity, which the intact S1A catalytic triad supports. The chymotrypsin-specific EC name is not taken as evidence of chymotrypsin-like (aromatic P1) specificity: the S1-pocket residue 189 is Gly and no substrate has been tested. Supporting Evidence: file:DROME/CG17404/CG17404-uniprot.txt DR InterPro; IPR001314; Peptidase_S1A. file:DROME/CG17404/CG17404-uniprot.txt DR Pfam; PF00089; Trypsin; 1. file:DROME/CG17404/CG17404-uniprot.txt DR PROSITE; PS00134; TRYPSIN_HIS; 1. file:DROME/CG17404/CG17404-uniprot.txt DR PROSITE; PS00135; TRYPSIN_SER; 1. file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md The three PROSITE-ProRule active-site positions carry the catalytic residues of an S1A serine protease: His80 (context ILTAAHCCQGL), Asp124 (context ELVTSDLAVLS) and Ser225 (context ACSGDSGGPLV). PMID:30367934 SPs or SPHs based on the presence or absence of the His-Asp-Ser catalytic triad |
| GO:0004252 serine-type endopeptidase activity | ISM PMID:12568721 Serine proteases and their homologs in the Drosophila melano... | ACCEPT | Summary: FlyBase sequence-model annotation from the Drosophila SP/SPH genome survey is consistent with the intact triad. Reason: PMID:12568721 (Ross et al. 2003) classified the Drosophila S1A genes into catalytic serine proteases (SPs) and homologs (SPHs) by sequence conservation. Only the abstract is cached, so the CG17404 entry cannot be read, but the classification as an SP agrees with the retained His80/Asp124/Ser225 in the target sequence. Supporting Evidence: PMID:12568721 established a framework of information about evolutionary relationships among file:DROME/CG17404/CG17404-uniprot.txt DR InterPro; IPR001314; Peptidase_S1A. file:DROME/CG17404/CG17404-uniprot.txt DR Pfam; PF00089; Trypsin; 1. file:DROME/CG17404/CG17404-uniprot.txt DR PROSITE; PS00134; TRYPSIN_HIS; 1. file:DROME/CG17404/CG17404-uniprot.txt DR PROSITE; PS00135; TRYPSIN_SER; 1. file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md The three PROSITE-ProRule active-site positions carry the catalytic residues of an S1A serine protease: His80 (context ILTAAHCCQGL), Asp124 (context ELVTSDLAVLS) and Ser225 (context ACSGDSGGPLV). PMID:30367934 SPs or SPHs based on the presence or absence of the His-Asp-Ser catalytic triad |
| GO:0004252 serine-type endopeptidase activity | ISM PMID:30367934 Building a platform for predicting functions of serine prote... | ACCEPT | Summary: The updated insect SP/SPH classification assigns catalytic status from the His-Asp-Ser triad, which CG17404 retains. Reason: PMID:30367934 divides Drosophila SP-related sequences into SPs and SPHs on the presence of the His-Asp-Ser triad. CG17404 retains all three residues in canonical contexts, so its classification as a catalytic SP and the resulting serine-type endopeptidase ISM annotation are sound. Supporting Evidence: file:DROME/CG17404/CG17404-uniprot.txt DR InterPro; IPR001314; Peptidase_S1A. file:DROME/CG17404/CG17404-uniprot.txt DR Pfam; PF00089; Trypsin; 1. file:DROME/CG17404/CG17404-uniprot.txt DR PROSITE; PS00134; TRYPSIN_HIS; 1. file:DROME/CG17404/CG17404-uniprot.txt DR PROSITE; PS00135; TRYPSIN_SER; 1. file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md The three PROSITE-ProRule active-site positions carry the catalytic residues of an S1A serine protease: His80 (context ILTAAHCCQGL), Asp124 (context ELVTSDLAVLS) and Ser225 (context ACSGDSGGPLV). PMID:30367934 SPs or SPHs based on the presence or absence of the His-Asp-Ser catalytic triad |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Extracellular location is supported by the signal peptide and the soluble single-domain architecture. Reason: The PTN001207268 IBD for extracellular region is inherited by Q9VGC0. The target has a SignalP signal peptide (1-20), no transmembrane segment or GPI signal, and only a short propeptide before the S1 domain, which fits a secreted soluble protease. No tissue or fluid (e.g. hemolymph or gut lumen) has been shown for CG17404, so the general term is as specific as the evidence allows. Supporting Evidence: file:DROME/CG17404/CG17404-uniprot.txt FT SIGNAL 1..20 FT /evidence="ECO:0000256|SAM:SignalP" file:DROME/CG17404/CG17404-uniprot.txt FT DOMAIN 35..274 FT /note="Peptidase S1" FT /evidence="ECO:0000259|PROSITE:PS50240" file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md Only 14 residues (RLNSRQPSGYTPHR, no cysteines) lie between the SignalP signal peptide (1..20) and the S1 domain. file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md The SF562 clade branches directly from PTN001207268, the Eumetazoa-level duplication node that also carries the PAINT IBD assertions for GO:0004252, GO:0006508 and GO:0005576 that Q9VGC0 inherits. |
| GO:0006508 proteolysis | IBA GO_REF:0000033 | ACCEPT | Summary: Proteolysis inherited from the PTN001207268 IBD is supported. Reason: Proteolysis is the general process carried out by an active serine endopeptidase. The gene product performs the hydrolysis itself, so it participates in the process. No substrate or physiological pathway is known, so the general term is the most specific process supported. Subfamily-specific processes of PTHR24256 relatives (Easter in dorsoventral patterning, Sp7 in prophenoloxidase activation, mammalian tryptases in mast-cell biology) sit in other clades and are not transferred. Supporting Evidence: file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md The SF562 clade branches directly from PTN001207268, the Eumetazoa-level duplication node that also carries the PAINT IBD assertions for GO:0004252, GO:0006508 and GO:0005576 that Q9VGC0 inherits. file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md None lies on the Q9VGC0 lineage. file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md The three PROSITE-ProRule active-site positions carry the catalytic residues of an S1A serine protease: His80 (context ILTAAHCCQGL), Asp124 (context ELVTSDLAVLS) and Ser225 (context ACSGDSGGPLV). PMID:30367934 SPs or SPHs based on the presence or absence of the His-Asp-Ser catalytic triad file:DROME/CG17404/CG17404-deep-research-falcon.md It would be inappropriate to assign CG17404 specifically to Toll signaling, prophenoloxidase activation, melanization, digestion, or development on current evidence. |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | ACCEPT | Summary: The InterPro2GO trypsin-domain mapping to proteolysis holds for this catalytically intact domain. Reason: Proteolysis is the general process carried out by an active serine endopeptidase. The gene product performs the hydrolysis itself, so it participates in the process. No substrate or physiological pathway is known, so the general term is the most specific process supported. Subfamily-specific processes of PTHR24256 relatives (Easter in dorsoventral patterning, Sp7 in prophenoloxidase activation, mammalian tryptases in mast-cell biology) sit in other clades and are not transferred. Supporting Evidence: file:DROME/CG17404/CG17404-uniprot.txt DR Pfam; PF00089; Trypsin; 1. file:DROME/CG17404/CG17404-uniprot.txt DR PROSITE; PS00134; TRYPSIN_HIS; 1. file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md The three PROSITE-ProRule active-site positions carry the catalytic residues of an S1A serine protease: His80 (context ILTAAHCCQGL), Asp124 (context ELVTSDLAVLS) and Ser225 (context ACSGDSGGPLV). |
| GO:0006508 proteolysis | ISM PMID:12568721 Serine proteases and their homologs in the Drosophila melano... | ACCEPT | Summary: Sequence-model annotation to proteolysis from the Drosophila SP survey is consistent with the intact triad. Reason: Proteolysis is the general process carried out by an active serine endopeptidase. The gene product performs the hydrolysis itself, so it participates in the process. No substrate or physiological pathway is known, so the general term is the most specific process supported. Subfamily-specific processes of PTHR24256 relatives (Easter in dorsoventral patterning, Sp7 in prophenoloxidase activation, mammalian tryptases in mast-cell biology) sit in other clades and are not transferred. PMID:12568721 is abstract-only in the cache. Supporting Evidence: PMID:12568721 established a framework of information about evolutionary relationships among file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md The three PROSITE-ProRule active-site positions carry the catalytic residues of an S1A serine protease: His80 (context ILTAAHCCQGL), Asp124 (context ELVTSDLAVLS) and Ser225 (context ACSGDSGGPLV). PMID:30367934 SPs or SPHs based on the presence or absence of the His-Asp-Ser catalytic triad |
| GO:0008233 peptidase activity | IEA GO_REF:0000104 | MODIFY | Summary: Peptidase activity is correct but less specific than the supported serine-type endopeptidase activity. Reason: The term is true of CG17404 but is an ancestor of GO:0004252 serine-type endopeptidase activity, which the gene already carries (IBA, IEA, ISM) and which the intact S1A catalytic triad supports. Replace with the specific term. Proposed replacements: serine-type endopeptidase activity Supporting Evidence: file:DROME/CG17404/CG17404-uniprot.txt DR InterPro; IPR001314; Peptidase_S1A. file:DROME/CG17404/CG17404-uniprot.txt DR Pfam; PF00089; Trypsin; 1. file:DROME/CG17404/CG17404-uniprot.txt DR PROSITE; PS00134; TRYPSIN_HIS; 1. file:DROME/CG17404/CG17404-uniprot.txt DR PROSITE; PS00135; TRYPSIN_SER; 1. file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md The three PROSITE-ProRule active-site positions carry the catalytic residues of an S1A serine protease: His80 (context ILTAAHCCQGL), Asp124 (context ELVTSDLAVLS) and Ser225 (context ACSGDSGGPLV). PMID:30367934 SPs or SPHs based on the presence or absence of the His-Asp-Ser catalytic triad |
| GO:0016787 hydrolase activity | IEA GO_REF:0000104 | MODIFY | Summary: Hydrolase activity is correct but less specific than the supported serine-type endopeptidase activity. Reason: The term is true of CG17404 but is an ancestor of GO:0004252 serine-type endopeptidase activity, which the gene already carries (IBA, IEA, ISM) and which the intact S1A catalytic triad supports. Replace with the specific term. Proposed replacements: serine-type endopeptidase activity Supporting Evidence: file:DROME/CG17404/CG17404-uniprot.txt DR InterPro; IPR001314; Peptidase_S1A. file:DROME/CG17404/CG17404-uniprot.txt DR Pfam; PF00089; Trypsin; 1. file:DROME/CG17404/CG17404-uniprot.txt DR PROSITE; PS00134; TRYPSIN_HIS; 1. file:DROME/CG17404/CG17404-uniprot.txt DR PROSITE; PS00135; TRYPSIN_SER; 1. file:DROME/CG17404/CG17404-bioinformatics/RESULTS-rereview.md The three PROSITE-ProRule active-site positions carry the catalytic residues of an S1A serine protease: His80 (context ILTAAHCCQGL), Asp124 (context ELVTSDLAVLS) and Ser225 (context ACSGDSGGPLV). PMID:30367934 SPs or SPHs based on the presence or absence of the His-Asp-Ser catalytic triad |
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Download this section (compressed HTML)Q: Is the S1 specificity pocket of CG17404 (Gly at chymotrypsin position 189) compatible with chymotrypsin-like aromatic P1 cleavage, as the PROSITE-derived EC 3.4.21.1 name implies, or with some other P1 preference?
Q: Are CG17404, CG12256 and CG3916, the three tandem SF562 paralogs, functionally redundant, and which enzyme activates their zymogens?
Experiment: Express CG17404 as a zymogen, activate it by cleavage at R34-I35 (for example with enterokinase after engineering a site), and profile its P1-P4 specificity with positional-scanning fluorogenic peptide libraries. Use an S225A mutant as a negative control.
Experiment: Map CG17404 expression by tissue (RNA in situ or a tagged knock-in), then test a CRISPR deletion of the CG17404/CG12256/CG3916 cluster for digestive, immune (melanization, Toll output) or developmental phenotypes.
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The substrates, cleavage specificity, activating protease, tissue of expression and physiological role of CG17404 are unknown. No member of its PANTHER subfamily (SF562) has been characterised.
BIOLOGY BP_DARK
What is known: Established by sequence only: secretion signal, an intact catalytic triad, a predicted R34-I35 zymogen activation site, and placement in an SF562 clade that diverged from the characterised tryptase and Easter/Sp7 clades at a Eumetazoa-level duplication.
Significance: Decides whether this conserved but neglected lineage (also present in mosquito, beetle and Trichoplax) is a digestive, immune or developmental protease. It also decides whether homology transfer from any characterised PTHR24256 clade is ever justified for SF562.
What would resolve it: Recombinant expression and activation of the zymogen, followed by peptide-library and proteome-wide (N-terminomics) cleavage assays; tissue expression mapping; and loss-of-function alleles covering the tandem CG17404/CG12256/CG3916 cluster.
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