CSN5

UniProt ID: A0A0B4KHM2
Organism: Drosophila melanogaster
Review Status: DRAFT
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Gene Description

CSN5 is the JAMM-family catalytic subunit of the COP9 signalosome, which removes Nedd8 from cullin proteins and regulates cullin-RING ubiquitin ligases. Its metalloprotease activity depends on assembly with other signalosome subunits. The native 325-residue PB isoform retains the MPN domain and JAMM metal-binding motif of the characterized PA product. CSN5 acts in nuclear and cytoplasmic regulatory complexes and supports diverse developmental processes.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005634 nucleus
IEA
GO_REF:0000044 		ACCEPT
Summary: The characterized same-gene CSN5 protein occurs in nuclear and cytoplasmic signalosome pools.
Reason: The characterized same-gene CSN5 protein occurs in nuclear and cytoplasmic signalosome pools. PB retains the catalytic MPN/JAMM region and differs only by two residues outside it, supporting transfer of the broad compartment assignment; no exact PB imaging experiment is asserted.
Supporting Evidence:
file:DROME/CSN5/CSN5-bioinformatics/RESULTS.md
The MPN domain 52–189 and JAMM motif 135–148 are completely retained, including His135, His137 and Asp148.
file:DROME/CSN5/CSN5-reference-Q9XZ58-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
GO:0005737 cytoplasm
IEA
GO_REF:0000044 		ACCEPT
Summary: The characterized same-gene CSN5 protein occurs in nuclear and cytoplasmic signalosome pools.
Reason: The characterized same-gene CSN5 protein occurs in nuclear and cytoplasmic signalosome pools. PB retains the catalytic MPN/JAMM region and differs only by two residues outside it, supporting transfer of the broad compartment assignment; no exact PB imaging experiment is asserted.
Supporting Evidence:
file:DROME/CSN5/CSN5-bioinformatics/RESULTS.md
The MPN domain 52–189 and JAMM motif 135–148 are completely retained, including His135, His137 and Asp148.
file:DROME/CSN5/CSN5-reference-Q9XZ58-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
GO:0008233 peptidase activity
IEA
GO_REF:0000002 		MODIFY
Summary: The specific supported reaction is metal-dependent removal of Nedd8 from cullins, carried out by CSN5 within the COP9 signalosome.
Reason: The specific supported reaction is metal-dependent removal of Nedd8 from cullins, carried out by CSN5 within the COP9 signalosome. The complete JAMM motif is retained in PB. Generic peptidase activity loses both substrate and complex specificity; use metal-dependent deNEDDylase activity, with the complex-dependent contribution stated explicitly.
Supporting Evidence:
PMID:12183637
The Jab1/MPN domain metalloenzyme (JAMM) motif in the Jab1/Csn5 subunit was found to underlie CSN's Nedd8 isopeptidase activity.
file:DROME/CSN5/CSN5-reference-Q9XZ58-uniprot.txt
it probably acts as the CC catalytic center that mediates the cleavage of Nedd8 from cullins. It CC however has no metalloprotease activity by itself and requires the CC other subunits of the CSN complex.
file:DROME/CSN5/CSN5-bioinformatics/RESULTS.md
The MPN domain 52–189 and JAMM motif 135–148 are completely retained, including His135, His137 and Asp148.
GO:0008180 COP9 signalosome
ISS
PMID:10531038
The COP9 signalosome is essential for development of Drosoph... 		NEW
Summary: CSN5 is a COP9 signalosome component; the native PB product retains the full MPN/JAMM architecture of the characterized same-gene PA protein.
Reason: The primary fly study isolated all eight COP9 components and established complex association by co-immunoprecipitation and gel filtration. The exact PB product differs by only two residues outside the MPN domain; the retained architecture supports transfer of complex membership, without claiming direct experimental isolation of PB.
Supporting Evidence:
PMID:10531038
we have isolated Drosophila melanogaster genes encoding eight subunits of the COP9 signalosome, and have shown by co-immunoprecipitation and gel-filtration analysis that these proteins are components of the Drosophila COP9 signalosome.
file:DROME/CSN5/CSN5-bioinformatics/RESULTS.md
The MPN domain 52–189 and JAMM motif 135–148 are completely retained, including His135, His137 and Asp148.

Core Functions

Supplies the JAMM catalytic center for cullin deneddylation within the COP9 signalosome.

In Complex:
COP9 signalosome
Supporting Evidence:
  • PMID:12183637
    The Jab1/MPN domain metalloenzyme (JAMM) motif in the Jab1/Csn5 subunit was found to underlie CSN's Nedd8 isopeptidase activity.
  • file:DROME/CSN5/CSN5-reference-Q9XZ58-uniprot.txt
    it probably acts as the CC catalytic center that mediates the cleavage of Nedd8 from cullins. It CC however has no metalloprotease activity by itself and requires the CC other subunits of the CSN complex.
  • file:DROME/CSN5/CSN5-bioinformatics/RESULTS.md
    The MPN domain 52–189 and JAMM motif 135–148 are completely retained, including His135, His137 and Asp148.

References

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External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM2 External predictions

View prediction review YAML · CSN5-protnlm-predictions-review.yaml · Review status: COMPLETE

CSN5 has a supported signalosome catalytic role, but synaptic-vesicle localization is unverified for the selected PB isoform.

Source documents: genes/DROME/CSN5/CSN5-protnlm-source.json · genes/DROME/CSN5/CSN5-bioinformatics/RESULTS.md

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0008021 synaptic vesicle GO_CC
UNC — Uncertain Review score: 1/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08 · file:DROME/CSN5/CSN5-protnlm-source.json
Review rationale: The target is a near-identical CSN5 splice product retaining the complete JAMM catalytic domain. Primary evidence establishes the COP9 deneddylation mechanism, including roles in neural development, but those processes do not establish physical residence in synaptic vesicles. The source donor Q6GLM9 is a homologous protein and its compartment label is not a substitute for target vesicle localization. No vesicle-specific microscopy, fractionation or supported conserved vesicle-targeting feature validates or refutes the claim. The term is absent from target GOA.
Supporting Evidence:
  • file:DROME/CSN5/CSN5-bioinformatics/RESULTS.md: "The MPN domain 52–189 and JAMM motif 135–148 are completely retained, including His135, His137 and Asp148."
  • PMID:12183637: "The Jab1/MPN domain metalloenzyme (JAMM) motif in the Jab1/Csn5 subunit was found to underlie CSN's Nedd8 isopeptidase activity."

Deep Research

Falcon

(CSN5-deep-research-falcon.md)

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📚 Additional Documentation

Notes

(CSN5-notes.md)

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Bioinformatics Results

(RESULTS.md)

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📄 View Raw YAML

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