CG33090

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds	IEA GO_REF:0000002	UNDECIDED	Summary: The exact target is native PC (X2JE45), which differs from the longer PB isoform in its N-terminal GH116 region. Reason: The exact target is native PC (X2JE45), which differs from the longer PB isoform in its N-terminal GH116 region. Its conserved catalytic Glu362 and Asp575 support hydrolase potential, but 177 PB N-terminal residues are replaced by a distinct 28-residue segment. Primary human GBA2 isoform experiments show that N-terminal alterations can abolish activity despite expression. Those changes are not identical to fly PC, so neither catalytic activity nor inactivity is established for this particular isoform; an isoform-resolved assay is needed. Supporting Evidence: file:DROME/CG33090/CG33090-bioinformatics/RESULTS.md Both global and local MAFFT alignments map human GBA2 Glu527 to PC Glu362 and Asp677 to PC Asp575 (PB Glu511 and Asp724). The catalytic nucleophile and acid/base residue types are retained. file:DROME/CG33090/CG33090-bioinformatics/RESULTS.md PC has a distinct 28-residue N-terminus followed by a 771-residue sequence identical to PB residues 178–948. PMID:33261081 Thus, all human GBA2 isoforms were expressed but only isoform 1 clearly hydrolyzed the MUG substrate.
GO:0005975 carbohydrate metabolic process	IEA GO_REF:0000002	UNDECIDED	Summary: The exact target is native PC (X2JE45), which differs from the longer PB isoform in its N-terminal GH116 region. Reason: The exact target is native PC (X2JE45), which differs from the longer PB isoform in its N-terminal GH116 region. Its conserved catalytic Glu362 and Asp575 support hydrolase potential, but 177 PB N-terminal residues are replaced by a distinct 28-residue segment. Primary human GBA2 isoform experiments show that N-terminal alterations can abolish activity despite expression. Those changes are not identical to fly PC, so neither catalytic activity nor inactivity is established for this particular isoform; an isoform-resolved assay is needed. Supporting Evidence: file:DROME/CG33090/CG33090-bioinformatics/RESULTS.md Both global and local MAFFT alignments map human GBA2 Glu527 to PC Glu362 and Asp677 to PC Asp575 (PB Glu511 and Asp724). The catalytic nucleophile and acid/base residue types are retained. file:DROME/CG33090/CG33090-bioinformatics/RESULTS.md PC has a distinct 28-residue N-terminus followed by a 771-residue sequence identical to PB residues 178–948. PMID:33261081 Thus, all human GBA2 isoforms were expressed but only isoform 1 clearly hydrolyzed the MUG substrate.

GO Term

Evidence

Action

Reason

GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds

IEA
GO_REF:0000002

UNDECIDED

Summary: The exact target is native PC (X2JE45), which differs from the longer PB isoform in its N-terminal GH116 region.

Reason: The exact target is native PC (X2JE45), which differs from the longer PB isoform in its N-terminal GH116 region. Its conserved catalytic Glu362 and Asp575 support hydrolase potential, but 177 PB N-terminal residues are replaced by a distinct 28-residue segment. Primary human GBA2 isoform experiments show that N-terminal alterations can abolish activity despite expression. Those changes are not identical to fly PC, so neither catalytic activity nor inactivity is established for this particular isoform; an isoform-resolved assay is needed.

Supporting Evidence:

file:DROME/CG33090/CG33090-bioinformatics/RESULTS.md

Both global and local MAFFT alignments map human GBA2 Glu527 to PC Glu362 and Asp677 to PC Asp575 (PB Glu511 and Asp724). The catalytic nucleophile and acid/base residue types are retained.

file:DROME/CG33090/CG33090-bioinformatics/RESULTS.md

PC has a distinct 28-residue N-terminus followed by a 771-residue sequence identical to PB residues 178–948.

PMID:33261081

Thus, all human GBA2 isoforms were expressed but only isoform 1 clearly hydrolyzed the MUG substrate.

GO:0005975 carbohydrate metabolic process

IEA
GO_REF:0000002

UNDECIDED

Summary: The exact target is native PC (X2JE45), which differs from the longer PB isoform in its N-terminal GH116 region.

Supporting Evidence:

file:DROME/CG33090/CG33090-bioinformatics/RESULTS.md

Both global and local MAFFT alignments map human GBA2 Glu527 to PC Glu362 and Asp677 to PC Asp575 (PB Glu511 and Asp724). The catalytic nucleophile and acid/base residue types are retained.

file:DROME/CG33090/CG33090-bioinformatics/RESULTS.md

PC has a distinct 28-residue N-terminus followed by a 771-residue sequence identical to PB residues 178–948.

PMID:33261081

Thus, all human GBA2 isoforms were expressed but only isoform 1 clearly hydrolyzed the MUG substrate.

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 · CG33090-protnlm-predictions-review.yaml · Review status: COMPLETE

Hydrolase activity is plausible from the conserved GBA2 catalytic core, but remains unresolved for the distinct native PC N-terminal architecture.

Source documents: projects/PROTNLM_EVALUATION/fly-benchmark/predictions.jsonl.gz · genes/DROME/CG33090/CG33090-predictions-source.json

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

GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds GO_MF

UNC — Uncertain Review score: 1/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08

Review rationale: X2JE45 is the native 799-residue PC isoform. It retains the catalytic residues corresponding to human GBA2 Glu527 and Asp677, but replaces PB residues 1–177 with a distinct 28-residue N-terminus that alters the GH116 N-terminal region. Human GBA2 isoform experiments establish that such noncatalytic-domain changes can impair activity; they do not demonstrate that this different fly isoform is inactive. The specific missing evidence is activity or fold integrity of native PC, rather than uncertainty about the GBA2 family as a whole.

Supporting Evidence:

file:DROME/CG33090/CG33090-bioinformatics/RESULTS.md: "Both global and local MAFFT alignments map human GBA2 Glu527 to PC Glu362 and Asp677 to PC Asp575 (PB Glu511 and Asp724). The catalytic nucleophile and acid/base residue types are retained."
file:DROME/CG33090/CG33090-bioinformatics/RESULTS.md: "PC has a distinct 28-residue N-terminus followed by a 771-residue sequence identical to PB residues 178–948."
PMID:33261081: "Thus, all human GBA2 isoforms were expressed but only isoform 1 clearly hydrolyzed the MUG substrate."

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Bioinformatics Results

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Gene Description

Existing Annotations Review

References

External Prediction Reviews

ProtNLM2 External predictions

Deep Research

Falcon

📚 Additional Documentation

Notes

Bioinformatics Results

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