lspA encodes lipoprotein signal peptidase II, a multi-pass inner-membrane peptidase A8/aspartyl protease that removes signal peptides from diacylglyceryl-modified bacterial prolipoproteins. In the canonical bacterial lipoprotein maturation pathway, LspA acts after Lgt installs the diacylglyceryl group on the lipobox cysteine and before Lnt performs terminal N-acylation.
Definition: Catalysis of the hydrolysis of the signal peptide from a bacterial membrane diacylglyceryl-prolipoprotein, cleaving immediately N-terminal to the lipid-modified lipobox cysteine.
Justification: GOA currently represents LspA with the broad parent GO:0004190 aspartic-type endopeptidase activity, but LspA is a specific signal peptidase II/prolipoprotein signal peptidase with defined substrate context and pathway order.
Parent term: aspartic-type endopeptidase activity
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004190 aspartic-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: LspA is a membrane-embedded peptidase A8/aspartyl protease that removes the signal peptide from diacylglyceryl-modified prolipoproteins. Reason: GO:0004190 is broad, but it correctly captures the catalytic class currently available in GOA for LspA. UniProt assigns EC 3.4.23.36, names the protein lipoprotein signal peptidase, and annotates two aspartate active-site residues. A more specific lipoprotein signal peptidase molecular-function term would be preferable if GO adds one. Supporting Evidence: file:PSEPK/lspA/lspA-uniprot.txt RecName: Full=Lipoprotein signal peptidase file:PSEPK/lspA/lspA-uniprot.txt EC=3.4.23.36 file:PSEPK/lspA/lspA-uniprot.txt Reaction=Release of signal peptides from bacterial membrane file:PSEPK/lspA/lspA-goa.tsv GO:0004190 aspartic-type endopeptidase activity file:PSEPK/lspA/lspA-deep-research-openscientist.md It is an essential, integral inner-membrane **aspartyl protease** |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Plasma membrane is the correct GO cellular-component term for bacterial inner-membrane LspA. Reason: UniProt places LspA in the cell inner membrane as a multi-pass membrane protein, and GOA records the corresponding bacterial plasma membrane localization. Supporting Evidence: file:PSEPK/lspA/lspA-uniprot.txt SUBCELLULAR LOCATION: Cell inner membrane file:PSEPK/lspA/lspA-uniprot.txt Multi-pass membrane protein file:PSEPK/lspA/lspA-goa.tsv GO:0005886 plasma membrane |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Proteolysis is technically true but too broad for LspA's role in bacterial lipoprotein maturation. Reason: LspA does not act as a general protease; it cleaves signal peptides from diacylglyceryl-modified prolipoproteins in the lipoprotein biosynthetic pathway. The separate NEW GO:0042158 annotation captures that process without creating a duplicate replacement landing point. Supporting Evidence: file:PSEPK/lspA/lspA-uniprot.txt PATHWAY: Protein modification; lipoprotein biosynthesis (signal peptide file:PSEPK/lspA/lspA-uniprot.txt This protein specifically catalyzes the removal of signal file:PSEPK/lspA/lspA-goa.tsv GO:0006508 proteolysis |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: The membrane annotation is correct but less precise than plasma membrane for this bacterial inner-membrane enzyme. Reason: InterPro supports a membrane-associated LspA family assignment, but UniProt and GOA already provide the more precise bacterial plasma membrane annotation. Proposed replacements: plasma membrane Supporting Evidence: file:PSEPK/lspA/lspA-uniprot.txt SUBCELLULAR LOCATION: Cell inner membrane file:PSEPK/lspA/lspA-goa.tsv GO:0016020 membrane |
| GO:0042158 lipoprotein biosynthetic process | ISS file:PSEPK/lspA/lspA-uniprot.txt | NEW | Summary: LspA is the signal-peptide cleavage step of bacterial lipoprotein biosynthesis. Reason: UniProt explicitly places LspA in protein modification, lipoprotein biosynthesis, signal peptide cleavage. This process term is present for lgt and lnt and should also cover the intervening LspA step. Supporting Evidence: file:PSEPK/lspA/lspA-uniprot.txt PATHWAY: Protein modification; lipoprotein biosynthesis (signal peptide file:PSEPK/lspA/lspA-deep-research-openscientist.md performs the committed, second step of the universal bacterial lipoprotein biogenesis pathway |
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Download this section (compressed HTML)Q: Should GO add a specific lipoprotein signal peptidase activity term for bacterial LspA/SPase II rather than relying on broad aspartic-type endopeptidase activity?
Suggested experts: GO molecular function curators
Q: Is PP_0604 essential under standard KT2440 growth conditions, and what lipoprotein substrates accumulate when LspA activity is inhibited or depleted?
Suggested experts: Pseudomonas envelope biogenesis experts
Experiment: Construct a conditional lspA depletion strain and assay accumulation of unprocessed prolipoproteins, envelope stress, and growth defects.
Type: conditional depletion and lipoproteomics
Experiment: Reconstitute PP_0604 in membrane mimetics with diacylglyceryl-prolipoprotein peptide substrates and test cleavage plus globomycin/myxovirescin inhibition.
Type: in vitro peptidase assay
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