mucD (algY, PA0766) encodes MucD, a periplasmic HtrA/DegP-family serine protease (peptidase S1C) with a trypsin-like protease domain and two PDZ domains. It is the last gene of the algU-mucA-mucB-mucC-mucD operon. MucD degrades unfolded proteins in the periplasm, preferring small hydrophobic P1 residues, and its proteolytic activity is governed by an equilibrium between a resting 12-mer cage and an active trimer. It is a negative regulator of alginate production at two levels. Loss of MucD lets the anti-sigma factor MucA be degraded by the intramembrane protease MucP, even without AlgW, which releases the sigma factor AlgU and activates the algD alginate operon. MucD also binds and degrades the periplasmic alginate biosynthesis proteins AlgK and AlgX. mucD mutants are mucoid and more sensitive to heat and hydrogen peroxide.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0042597 periplasmic space | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN002342204, whose periplasmic space IBD is seeded only by this gene's own PseudoCAP IDA row. The target in its own WITH/FROM is expected. Reason: MucD has a predicted Sec signal peptide, belongs to the periplasmic DegP clade, was found in a periplasmic complex with AlgK and AlgX, and degrades those periplasmic proteins in vitro. The node's leaves are all DegP-like proteases, for which the periplasm is the expected location, so the IBD is sound. Supporting Evidence: PMID:21713511 Experimental evidence was provided for a periplasmic multiprotein complex composed of AlgX, AlgK, and the regulatory protein MucD. file:PSEAE/mucD/mucD-uniprot.txt SIGNAL 1..25 |
| GO:0004252 serine-type endopeptidase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro peptidase S1C / Do-family mapping. Reason: Correct and core. Purified MucD degrades AlgK and AlgX, and the catalytic serine mutant S217A is the inactive form used for structures. Supporting Evidence: PMID:42766672 In contrast, isolated AlgK and AlgX were completely degraded by MucD within 2 h of incubation (Figs 1B and S1C–S1E). file:PSEAE/mucD/mucD-uniprot.txt InterPro; IPR011782; Pept_S1C_Do. |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping to proteolysis. Reason: MucD is an active endoprotease that degrades whole periplasmic proteins in vitro. GO has no more specific periplasmic-degradation process term that the evidence supports, so proteolysis is the appropriate level. Supporting Evidence: PMID:42766672 Collectively, these results suggest that MucD can alternatively regulate alginate production by directly degrading alginate biosynthetic proteins. |
| GO:0042597 periplasmic space | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to periplasm. Reason: The UniProt location line is ARBA-derived, but the claim is independently supported by the signal peptide and the periplasmic complex with AlgK and AlgX. Supporting Evidence: PMID:21713511 Experimental evidence was provided for a periplasmic multiprotein complex composed of AlgX, AlgK, and the regulatory protein MucD. |
| GO:0004252 serine-type endopeptidase activity | ISS PMID:16376476 Biochemical analysis of alginate biosynthesis protein AlgX f... | ACCEPT | Summary: PseudoCAP ISS with E. coli DegP (NP_414703.1), referenced to the AlgX-MucD complex paper. Reason: The claim is correct and now directly shown for MucD. The cited paper only reports an AlgX-MucD complex and has no protease assay, so it is a weak reference for this row, but the ISS rests on DegP similarity, which is sound. Supporting Evidence: PMID:42766672 In contrast, isolated AlgK and AlgX were completely degraded by MucD within 2 h of incubation (Figs 1B and S1C–S1E). file:PSEAE/mucD/mucD-uniprot.txt MEROPS; S01.453; -. |
| GO:0007165 signal transduction | IDA PMID:21036998 Pseudomonas aeruginosa MucD regulates the alginate pathway t... | MODIFY | Summary: PseudoCAP IDA. Damron and Yu showed that in a mucD mutant MucA is degraded through MucP, bypassing AlgW, and AlgU is activated. Reason: The paper is genetic (mutants, algU-promoter reporter, Western blots of tagged MucA), so the evidence is IMP, not IDA. It shows that MucD restrains the MucA proteolytic cascade that transmits envelope signals to AlgU, so MucD is a negative regulator of that signal transduction, not a component of it. Whether it acts by degrading activating signals or the alginate machinery is unresolved. Proposed replacements: negative regulation of signal transduction Supporting Evidence: PMID:21036998 When mucD is inactivated, a high level of algU promoter activity was noted (Fig. 3A ), suggesting that the RIP activities are negatively regulated by MucD. |
| GO:0042597 periplasmic space | IDA PMID:21713511 Identification of a periplasmic AlgK-AlgX-MucD multiprotein ... | ACCEPT | Summary: PseudoCAP IDA; sole seed of the PTN002342204 periplasmic space IBD (5 leaf IBAs). Hay et al. identified a periplasmic AlgK-AlgX-MucD complex. Reason: The abstract explicitly reports MucD in a periplasmic complex, which a later paper describes as affinity pull-down evidence. Only the abstract is available, so the fractionation method could not be checked, but the claim agrees with the signal peptide, the DegP family and the in vitro degradation of periplasmic AlgK and AlgX. The seed is sound. Supporting Evidence: PMID:21713511 Experimental evidence was provided for a periplasmic multiprotein complex composed of AlgX, AlgK, and the regulatory protein MucD. PMID:42766672 Affinity pull-down studies further suggested that MucD could form a periplasmic complex with the terminal acetyltransferase AlgX and tetratricopeptide repeat (TPR)-rich scaffold protein AlgK [14]. |
Loading supporting content…
Download this section (compressed HTML)Q: Does MucD restrain MucP-dependent MucA cleavage by degrading envelope signals, by degrading MucA-associated factors, or through its effect on AlgK/AlgX?
Experiment: Compare MucA stability and AlgU activity in a mucD deletion complemented with wild-type MucD, catalytic S217A MucD, or the 12-mer-locked variant, and identify periplasmic proteins that accumulate in the mutant by proteomics.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)