CG30287

UniProt ID: Q8MLV8
Organism: Drosophila melanogaster
Review Status: DRAFT
📝 Provide Detailed Feedback

Gene Description

CG30287 (also called SP224, and historically SPH37) encodes a predicted secreted serine endopeptidase of the S1A (trypsin/chymotrypsin) family. The 284-residue protein has an N-terminal signal peptide, a 20-residue propeptide with no clip domain, and a single Peptidase S1 domain. That domain has an intact His82-Asp136-Ser232 catalytic triad and a candidate activation cleavage site after Arg41. It belongs to an insect-specific PANTHER subfamily (PTHR24256:SF553) of uncharacterized Drosophila paralogs that includes Jon99Ciii and CG4914. Its substrate specificity, activating protease, tissue of action and biological role have not been studied.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004252 serine-type endopeptidase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: Inherited serine-type endopeptidase activity is consistent with the sequence and the PAINT tree.
Reason: The IBD sits at the deep node PTN001207268. Easter (FBgn0000533) is among its donors. PAINT curators carved out the lineages that lost the catalytic triad with NOT|GO:0004252 IKR nodes, and none of them is an ancestor of CG30287 in the PANTHER 19.0 tree. The exact sequence keeps His82, Asp136 and Ser232 in a canonical GDSGGP motif, so the "SPH37" name (serine protease homolog) does not indicate a loss of catalysis. No activity has been measured.
Supporting Evidence:
file:DROME/CG30287/CG30287-bioinformatics/RESULTS-rereview.md
CG30287 is not under any NOT node.
file:DROME/CG30287/CG30287-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His82 (in TAAHC), Asp136 and Ser232 in the canonical GDSGGP motif.
PMID:30367934
The SP-related sequences in each species were divided into SPs or SPHs
GO:0004252 serine-type endopeptidase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Same claim as the IBA, reached from domain signatures.
Reason: A trypsin-domain signature and an intact catalytic triad support broad serine-endopeptidase activity. The EC 3.4.21.1 (chymotrypsin) mapping in the WITH column is not adopted as a statement of specificity. The S1-pocket residue at chymotrypsin position 189 is Ser226, and the other pocket positions were not mapped, so the P1 preference is unknown.
Supporting Evidence:
file:DROME/CG30287/CG30287-uniprot.txt
DR InterPro; IPR001254; Trypsin_dom.
file:DROME/CG30287/CG30287-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His82 (in TAAHC), Asp136 and Ser232 in the canonical GDSGGP motif.
GO:0004252 serine-type endopeptidase activity
ISM
PMID:30367934
Building a platform for predicting functions of serine prote... 		ACCEPT
Summary: FlyBase sequence-model call, consistent with the retained triad.
Reason: PMID:30367934 classified Drosophila SP-related proteins as SPs or SPHs by whether the His-Asp-Ser triad is retained. The current CG30287 sequence retains all three residues, which supports the SP (catalytic) assignment behind this ISM row despite the older SPH37 name.
Supporting Evidence:
PMID:30367934
The SP-related sequences in each species were divided into SPs or SPHs
file:DROME/CG30287/CG30287-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His82 (in TAAHC), Asp136 and Ser232 in the canonical GDSGGP motif.
GO:0005576 extracellular region
IBA
GO_REF:0000033 		ACCEPT
Summary: Extracellular location is supported by the predicted signal peptide and the PAINT node.
Reason: A SignalP signal peptide at residues 1-21, no predicted transmembrane segment, and a soluble single S1 domain fit secretion. The IBD at PTN001207268 lies on the CG30287 lineage. Neither the tissue nor the compartment (for example hemolymph or gut lumen) has been determined.
Supporting Evidence:
file:DROME/CG30287/CG30287-uniprot.txt
FT SIGNAL 1..21
file:DROME/CG30287/CG30287-bioinformatics/RESULTS-rereview.md
CG30287 is not under any NOT node.
GO:0006508 proteolysis
IBA
GO_REF:0000033 		ACCEPT
Summary: Broad proteolysis follows from the inherited catalytic activity.
Reason: Proteolysis is as specific as the evidence allows. No substrate or physiological process is known, and CG30287 is not on the PAINT node that carries the innate-immune-response IBD (PTN000667087). No more specific process term is warranted.
Supporting Evidence:
file:DROME/CG30287/CG30287-bioinformatics/RESULTS-rereview.md
CG30287 is not under any NOT node.
file:DROME/CG30287/CG30287-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His82 (in TAAHC), Asp136 and Ser232 in the canonical GDSGGP motif.
GO:0006508 proteolysis
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro2GO proteolysis, consistent with the IBA.
Reason: The trypsin-domain and TRYPSIN_HIS signatures and the intact triad support proteolysis at this broad level, matching the IBA row.
Supporting Evidence:
file:DROME/CG30287/CG30287-uniprot.txt
DR InterPro; IPR001254; Trypsin_dom.
file:DROME/CG30287/CG30287-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His82 (in TAAHC), Asp136 and Ser232 in the canonical GDSGGP motif.
GO:0008233 peptidase activity
IEA
GO_REF:0000104 		MODIFY
Summary: Peptidase activity is correct but too general.
Reason: The intact S1 catalytic triad supports serine-type endopeptidase activity (GO:0004252), a descendant of this term that the gene already carries by IBA, IEA and ISM.
Supporting Evidence:
file:DROME/CG30287/CG30287-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His82 (in TAAHC), Asp136 and Ser232 in the canonical GDSGGP motif.
file:DROME/CG30287/CG30287-uniprot.txt
DR InterPro; IPR001254; Trypsin_dom.
GO:0016787 hydrolase activity
IEA
GO_REF:0000104 		MODIFY
Summary: Hydrolase activity is correct but uninformative.
Reason: The specific supported activity is serine-type endopeptidase activity (GO:0004252), a descendant that the gene already carries.
Supporting Evidence:
file:DROME/CG30287/CG30287-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His82 (in TAAHC), Asp136 and Ser232 in the canonical GDSGGP motif.
file:DROME/CG30287/CG30287-uniprot.txt
DR InterPro; IPR001254; Trypsin_dom.

Core Functions

Predicted secreted serine endopeptidase with an intact His-Asp-Ser catalytic triad, inherited from the ancestral PTHR24256 node at which PAINT places catalytic activity. Substrates and activation are unknown.

Molecular Function:
serine-type endopeptidase activity
Directly Involved In:
proteolysis
Cellular Locations:
extracellular region
Supporting Evidence:
  • file:DROME/CG30287/CG30287-bioinformatics/RESULTS-rereview.md
    The catalytic triad is intact: His82 (in TAAHC), Asp136 and Ser232 in the canonical GDSGGP motif.
  • file:DROME/CG30287/CG30287-bioinformatics/RESULTS-rereview.md
    CG30287 is not under any NOT node.
  • file:DROME/CG30287/CG30287-uniprot.txt
    FT SIGNAL 1..21

References

Loading supporting content…

Download this section (compressed HTML)

Suggested Questions for Experts

Q: Is CG30287 catalytically active after cleavage at Arg41, given its atypical VINGK mature N-terminus, and what is its P1 specificity?

Q: Do the nine Drosophila PTHR24256:SF553 paralogs, which include Jon99Ciii, form a gut-expressed digestive cluster, or are they secreted into hemolymph?

Suggested Experiments

Experiment: Express recombinant pro-CG30287, activate it with trypsin or enteropeptidase at Arg41, and profile its specificity with a positional-scanning fluorogenic peptide library. Use an S232A mutant as the inactive control.

Experiment: Test labelling of the endogenous protein by a fluorophosphonate activity-based probe in adult tissues, and map tissue expression with an endogenously tagged allele.

Deep Research

Falcon

(CG30287-deep-research-falcon.md)

Loading supporting content…

Download this section (compressed HTML)

📚 Additional Documentation

Notes

(CG30287-notes.md)

Loading supporting content…

Download this section (compressed HTML)

📄 View Raw YAML

Loading supporting content…

Download this section (compressed HTML)