CG30288

UniProt ID: Q8IRK6
Organism: Drosophila melanogaster
Review Status: DRAFT
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Gene Description

CG30288 (SP225) encodes a predicted secreted serine endopeptidase of the S1A (trypsin-like) family. The 282-residue protein has an N-terminal signal peptide, a short propeptide and a single S1 protease domain with an intact His-Asp-Ser catalytic triad (His83, Asp132, Ser225). Its protease domain is predicted to be activated by cleavage after Arg42. It has no clip domain. An aspartate at the base of the predicted S1 specificity pocket suggests trypsin-like preference for Arg or Lys at the cleavage site, rather than the chymotrypsin-like preference implied by its automatic name. CG30288 belongs to a Drosophila-specific PANTHER subfamily with three uncharacterized paralogs, including the neighbouring gene CG30289. Its physiological substrate, tissue of action and biological role have not been studied experimentally.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004252 serine-type endopeptidase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: Serine-type endopeptidase activity is supported by phylogeny and by an intact catalytic triad.
Reason: This IBA descends from PAINT node PTN001207268, whose IBD for GO:0004252 is seeded by experimentally characterised members (including Drosophila easter, FB:FBgn0000533). PAINT curators placed IKR NOT GO:0004252 losses on several descendant SPH clades; CG30288 (PANTHER subfamily PTHR24256:SF546) is not under any of those loss nodes, and its own sequence keeps His83, Asp132 and Ser225 in the GDSGGP motif. The inheritance is therefore consistent with the gene-specific sequence evidence. No substrate has been measured.
Supporting Evidence:
file:DROME/CG30288/CG30288-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His83 (TAEHC), Asp132 and Ser225 in the canonical GDSGGP motif.
file:DROME/CG30288/CG30288-uniprot.txt
FT DOMAIN 43..275 FT /note="Peptidase S1" FT /evidence="ECO:0000259|PROSITE:PS50240"
file:DROME/CG30288/CG30288-uniprot.txt
DR InterPro; IPR001314; Peptidase_S1A.
PMID:30367934
The SP-related sequences in each species were divided into 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: The serine-type endopeptidase class fits the sequence, but the chymotrypsin EC behind this mapping does not.
Reason: The InterPro/UniRule-combined IEA reaches the correct general term, serine-type endopeptidase activity, which matches the intact triad. The EC 3.4.21.1 (chymotrypsin) in WITH/FROM comes from a PROSITE-ProRule name assignment. The residue at the chymotrypsinogen position 189 of the S1 pocket is Asp219, which is the trypsin-like determinant, so chymotrypsin-like specificity should not be inferred. The GO term itself does not depend on that specificity.
Supporting Evidence:
file:DROME/CG30288/CG30288-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His83 (TAEHC), Asp132 and Ser225 in the canonical GDSGGP motif.
file:DROME/CG30288/CG30288-bioinformatics/RESULTS-rereview.md
An Asp at this position is the classical trypsin-like determinant, which favours Arg/Lys at P1.
file:DROME/CG30288/CG30288-uniprot.txt
FT DOMAIN 43..275 FT /note="Peptidase S1" FT /evidence="ECO:0000259|PROSITE:PS50240"
file:DROME/CG30288/CG30288-uniprot.txt
DR InterPro; IPR001314; Peptidase_S1A.
GO:0004252 serine-type endopeptidase activity
ISM
PMID:30367934
Building a platform for predicting functions of serine prote... 		ACCEPT
Summary: FlyBase sequence-model classification of CG30288 (SP225) as an active serine protease is coherent.
Reason: PMID:30367934 classified Drosophila SP-related genes as SPs or SPHs according to whether the His-Asp-Ser triad is retained, and CG30288 carries the SP name SP225, not an SPH name. The re-review sequence check confirms the triad. Its SP rather than cSP name, and its 19-residue propeptide, place it among the single-domain SPs rather than the CLIP-domain proteases.
Supporting Evidence:
PMID:30367934
The SP-related sequences in each species were divided into SPs or SPHs based on the presence or absence of the His-Asp-Ser catalytic triad
PMID:30367934
separated them into 57 gut SPs, 8 gut SPHs, 82 single-domain SPs, and 37
file:DROME/CG30288/CG30288-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His83 (TAEHC), Asp132 and Ser225 in the canonical GDSGGP motif.
file:DROME/CG30288/CG30288-bioinformatics/RESULTS-rereview.md
so CG30288 has a single protease domain and is not a CLIP-domain protease.
GO:0005576 extracellular region
IBA
GO_REF:0000033 		ACCEPT
Summary: Extracellular localization is supported.
Reason: The IBA descends from the PTN001207268 extracellular-region IBD. It is consistent with the target sequence, which has a SignalP signal peptide (1-23), no annotated transmembrane segment, and a zymogen-type propeptide followed by an S1 protease domain, the usual layout of secreted trypsin-like proteases. No direct localization data exist for CG30288, so the less specific extracellular region is kept rather than refined.
Supporting Evidence:
file:DROME/CG30288/CG30288-uniprot.txt
FT SIGNAL 1..23 FT /evidence="ECO:0000256|SAM:SignalP"
file:DROME/CG30288/CG30288-bioinformatics/RESULTS-rereview.md
The protease domain begins with IDGG, preceded by Arg42. This is a predicted zymogen activation site cleaved after Arg, i.e. by a trypsin-like protease.
GO:0006508 proteolysis
IBA
GO_REF:0000033 		ACCEPT
Summary: Proteolysis is the process directly carried out by this predicted active endopeptidase.
Reason: Proteolysis follows from the serine-endopeptidase activity inherited at PTN001207268 and retained in the sequence. A more specific process (for example Toll-pathway or melanization cascades) is not supported: CG30288 is not a CLIP protease, and no genetic or biochemical study places it in a pathway.
Supporting Evidence:
file:DROME/CG30288/CG30288-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His83 (TAEHC), Asp132 and Ser225 in the canonical GDSGGP motif.
file:DROME/CG30288/CG30288-uniprot.txt
FT DOMAIN 43..275 FT /note="Peptidase S1" FT /evidence="ECO:0000259|PROSITE:PS50240"
GO:0006508 proteolysis
IEA
GO_REF:0000002 		ACCEPT
Summary: Domain-to-proteolysis mapping is consistent with the retained catalytic triad.
Reason: The InterPro trypsin-domain mapping agrees with the IBA for the same term. Because the triad is retained, the domain implies a catalytic protease rather than a fold-only homolog.
Supporting Evidence:
file:DROME/CG30288/CG30288-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His83 (TAEHC), Asp132 and Ser225 in the canonical GDSGGP motif.
file:DROME/CG30288/CG30288-uniprot.txt
DR InterPro; IPR001254; Trypsin_dom.
GO:0008233 peptidase activity
IEA
GO_REF:0000104 		MODIFY
Summary: Correct but general; serine-type endopeptidase activity is supported.
Reason: Peptidase activity is true but less specific than the evidence allows. The S1A domain and intact His-Asp-Ser triad support GO:0004252 serine-type endopeptidase activity, which the gene already carries by IBA, IEA and ISM.
Supporting Evidence:
file:DROME/CG30288/CG30288-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His83 (TAEHC), Asp132 and Ser225 in the canonical GDSGGP motif.
file:DROME/CG30288/CG30288-uniprot.txt
DR InterPro; IPR001314; Peptidase_S1A.
GO:0016787 hydrolase activity
IEA
GO_REF:0000104 		MODIFY
Summary: Correct but general; serine-type endopeptidase activity is supported.
Reason: Hydrolase activity is true but uninformative. The S1A domain and intact triad support GO:0004252 serine-type endopeptidase activity, which the gene already carries.
Supporting Evidence:
file:DROME/CG30288/CG30288-bioinformatics/RESULTS-rereview.md
The catalytic triad is intact: His83 (TAEHC), Asp132 and Ser225 in the canonical GDSGGP motif.
file:DROME/CG30288/CG30288-uniprot.txt
DR InterPro; IPR001314; Peptidase_S1A.

Core Functions

Predicted secreted single-domain S1A serine endopeptidase with an intact catalytic triad and a trypsin-like S1 pocket. It is presumably activated from a zymogen and cleaves unidentified extracellular protein substrates.

Molecular Function:
serine-type endopeptidase activity
Directly Involved In:
proteolysis
Cellular Locations:
extracellular region
Supporting Evidence:
  • file:DROME/CG30288/CG30288-bioinformatics/RESULTS-rereview.md
    The catalytic triad is intact: His83 (TAEHC), Asp132 and Ser225 in the canonical GDSGGP motif.
  • file:DROME/CG30288/CG30288-bioinformatics/RESULTS-rereview.md
    An Asp at this position is the classical trypsin-like determinant, which favours Arg/Lys at P1.
  • PMID:30367934
    The SP-related sequences in each species were divided into SPs or SPHs based on the presence or absence of the His-Asp-Ser catalytic triad
  • file:DROME/CG30288/CG30288-uniprot.txt
    FT SIGNAL 1..23 FT /evidence="ECO:0000256|SAM:SignalP"

References

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Suggested Questions for Experts

Q: Is CG30288 catalytically active, and does it prefer Arg/Lys at P1 as its Asp at the S1-pocket position predicts, rather than the chymotrypsin-like specificity in its UniProt name?

Q: Do the four Drosophila-specific PTHR24256:SF546 paralogs (CG30288, CG30289, CG30414, SPH158) arise from recent tandem duplication, and do they share expression in fat body or another secreting tissue?

Suggested Experiments

Experiment: Express recombinant pro-CG30288, activate it with trypsin at Arg42, and profile P1 specificity with a positional-scanning fluorogenic peptide library; use an S225A mutant as the inactive control.

Experiment: Map the tissue and stage of expression with an endogenously tagged allele, and test secretion into hemolymph by proteomics.

Deep Research

Falcon

(CG30288-deep-research-falcon.md)

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📚 Additional Documentation

Notes

(CG30288-notes.md)

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