PA5134 encodes CtpA, a 436-residue carboxyl-terminal processing protease (CTP) of the peptidase S41A family in Pseudomonas aeruginosa PAO1, one of two CTPs in the genome alongside Prc (PA3257). It has a Sec signal peptide, a PDZ domain and an S41 serine-protease domain, and is a soluble periplasmic protein. A ctpA null mutant grows normally in the laboratory but has phenotypes consistent with an altered cell envelope, a defective type III secretion system, reduced cytotoxicity and attenuated virulence in a mouse acute pneumonia model, while raising CtpA levels induces an extracytoplasmic function sigma factor regulon. Its physiological substrates are not defined by the sources reviewed here.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004175 endopeptidase activity | IBA GO_REF:0000033 | TOO GENERAL | Summary: IBA endopeptidase activity from PTN000786001 (seeds B. subtilis CtpB and E. coli Prc). Reason: True, but entailed by the accepted GO:0004252 serine-type endopeptidase activity, which is_a endopeptidase activity. |
| GO:0004252 serine-type endopeptidase activity | ISS PMID:24928312 The lone S41 family C-terminal processing protease in Staphy... | ACCEPT | Summary: ISS from E. coli Prc (P23865), with the S. aureus CtpA paper as reference. CtpA belongs to the peptidase S41A family of serine C-terminal processing proteases. Reason: Correct catalytic activity from family membership (S41 serine protease domain). The cited reference is about S. aureus CtpA, but an ISS row only needs the similarity, and the term is right. Supporting Evidence: file:PSEAE/PA5134/PA5134-uniprot.txt Pfam; PF03572; Peptidase_S41; 1. PMID:21204920 Carboxy (C)-terminal processing proteases (CTP) are a relatively new group of serine proteases. |
| GO:0005886 plasma membrane | IDA PMID:21204920 The subcellular localization of a C-terminal processing prot... | UNDECIDED | Summary: PseudoCAP row from the Hoge et al. fractionation study, whose abstract reports a periplasmic location; a later study reports CtpA as a soluble periplasmic protein. Reason: The abstract does not mention a membrane fraction and the full text was not available; partial membrane association in a fractionation could underlie the row. Both abstracts place CtpA in the periplasm, so this row is doubtful but cannot be judged without the full text. |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO proteolysis from the S41A peptidase signatures. Reason: Correct process for a serine C-terminal processing protease. Supporting Evidence: file:PSEAE/PA5134/PA5134-uniprot.txt InterPro; IPR004447; Peptidase_S41A. |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA from PTN001279639, seeded by B. subtilis CtpB (O35002), P. aeruginosa Prc (Q9HYY3) and PA5134 itself. PA5134's own seed row cites an S. aureus paper and is removed in this review. Reason: No evidence seen here places CtpA in a signalling pathway. The remaining seeds are paralogous CTPs (CtpB, Prc) that each cleave an anti-sigma factor; that role does not transfer to CtpA without its own evidence, and the IBA reached PA5134 partly through its own mis-referenced seed. The tree (panther_tree.py, 2026-11-05) shows those two seeds lie on opposite sides of the duplication that defines this node - Prc in the SF22 branch, CtpB in a 2-leaf SF29 Bacillus clade - while PA5134 is SF30, so the term is held at the family root rather than at either lineage that supports it. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: SOURCE MISCITATION FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN001279639 · PTN001279639 UNRESOLVED Node spanning Prc-type and CtpA-type CTP subfamilies (58 leaves, 32 taxa). The topology (panther_tree.py, 2026-11-05) shows PTN001279639 is the DUPLICATION that separates the SF22 Prc branch (PTN004918760, 9 leaves) from the SF29/SF30 CtpA branch (PTN008644010, 49 leaves). Signal transduction is supported for CtpB (SF29) and Prc (SF22), which sit on opposite sides of that duplication, so the term was placed at their common ancestor - the root of the family - and reaches the whole SF30 CtpA clade that holds PA5134. UniProtKB:O35002 · B. subtilis CtpB SUPPORTS SOURCE BUT NOT TARGET CtpB cleaves SpoIVFA in sigma-K activation; sound for CtpB. UniProtKB:Q9HYY3 · P. aeruginosa Prc SUPPORTS SOURCE BUT NOT TARGET Prc removes the periplasmic anti-sigma domain in cell-surface signalling; sound for Prc. UniProtKB:Q9HU50 · PA5134 (self; PseudoCAP IDA PMID:24928312) SOURCE BAD Self-seed cites a Staphylococcus aureus paper with no signalling data. |
| GO:0007165 signal transduction | IDA PMID:24928312 The lone S41 family C-terminal processing protease in Staphy... | REMOVE | Summary: PseudoCAP row and a seed of the PTN001279639 IBD. The cited paper studies S. aureus CtpA and reports cell-wall localisation, stress sensitivity and virulence, not signal transduction. Reason: An S. aureus paper cannot give IDA evidence for a P. aeruginosa protein, and it reports no signalling role. No P. aeruginosa CtpA paper reviewed here shows CtpA acting in a signal transduction pathway. Supporting Evidence: PMID:24928312 Our results represent the first characterization of a C-terminal processing protease in a pathogenic Gram-positive bacterium |
| GO:0008236 serine-type peptidase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO serine-type peptidase from the S41A signatures. Reason: True, but entailed by the accepted GO:0004252 serine-type endopeptidase activity, which is_a serine-type peptidase activity. |
| GO:0030254 protein secretion by the type III secretion system | IMP PMID:24082078 The Pseudomonas aeruginosa periplasmic protease CtpA can aff... | MARK AS OVER ANNOTATED | Summary: PseudoCAP row. The ctpA null mutant has a defective T3SS and reduced cytotoxicity. Reason: CtpA is a periplasmic protease with envelope phenotypes; the T3SS defect is very likely a downstream consequence of altered envelope homeostasis rather than CtpA doing a step of type III secretion. Kept as a phenotype-level over-annotation rather than removed, since the full text was not read. Supporting Evidence: PMID:24082078 CtpA is essential for the normal function of the type 3 secretion system (T3SS) |
| GO:0030288 outer membrane-bounded periplasmic space | IBA GO_REF:0000033 | ACCEPT | Summary: IBA periplasmic location from PTN001279639 (seed E. coli Prc). Reason: Matches the fractionation data and the signal peptide. Supporting Evidence: PMID:24082078 We have now found that endogenous CtpA is a soluble periplasmic protein |
| GO:0030313 cell envelope | IDA PMID:21204920 The subcellular localization of a C-terminal processing prot... | MODIFY | Summary: PseudoCAP row from the Hoge et al. fractionation study. Reason: The study localises CtpA specifically to the periplasm; in GO the periplasmic space is not part_of cell envelope, so the specific location is given as the replacement rather than as a descendant. Proposed replacements: outer membrane-bounded periplasmic space Supporting Evidence: PMID:21204920 We show for the first time the subcellular localization of a CTP-3 family protein from Pseudomonas aeruginosa, named CtpA, in the periplasm |
| GO:0042546 cell wall biogenesis | IDA PMID:24928312 The lone S41 family C-terminal processing protease in Staphy... | REMOVE | Summary: PseudoCAP row citing the S. aureus CtpA paper, which reports cell-wall localisation of the S. aureus protein, not cell wall biogenesis by P. aeruginosa CtpA. Reason: Wrong organism and wrong claim: the paper has no P. aeruginosa data. The envelope role of PA5134 is captured by the cell envelope organization IMP row from PMID:24082078. Supporting Evidence: PMID:24928312 We demonstrate that S. aureus CtpA is localized to the bacterial cell wall |
| GO:0042597 periplasmic space | IDA PMID:21204920 The subcellular localization of a C-terminal processing prot... | MODIFY | Summary: PseudoCAP row; Hoge et al. fractionation places CtpA in the periplasm. Reason: Correct but general; P. aeruginosa is a diderm, so the specific term is GO:0030288 outer membrane-bounded periplasmic space, which the gene already carries by IBA. Proposed replacements: outer membrane-bounded periplasmic space Supporting Evidence: PMID:21204920 We show for the first time the subcellular localization of a CTP-3 family protein from Pseudomonas aeruginosa, named CtpA, in the periplasm |
| GO:0042597 periplasmic space | IDA PMID:24082078 The Pseudomonas aeruginosa periplasmic protease CtpA can aff... | MODIFY | Summary: PseudoCAP row; Seo and Darwin found endogenous CtpA to be a soluble periplasmic protein. Reason: Correct but general; the specific term for a diderm is GO:0030288, already carried by IBA. Proposed replacements: outer membrane-bounded periplasmic space Supporting Evidence: PMID:24082078 We have now found that endogenous CtpA is a soluble periplasmic protein |
| GO:0043163 cell envelope organization | IMP PMID:24082078 The Pseudomonas aeruginosa periplasmic protease CtpA can aff... | KEEP AS NON CORE | Summary: PseudoCAP row; the ctpA null mutant has phenotypes consistent with an altered cell envelope. Reason: Plausible for a periplasmic protease, but the abstract shows only envelope phenotypes, not which envelope step CtpA performs. Supporting Evidence: PMID:24082078 a ctpA null mutant has specific phenotypes consistent with an altered cell envelope |
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Q: Should the signal transduction IBD on PTN001279639 be moved to the CtpB and Prc subfamily nodes?
Experiment: Substrate trapping with a catalytic-serine CtpA mutant in the periplasm, followed by mass spectrometry, to identify the proteins CtpA cleaves.
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