MucA (PA0763) is the RseA-family inner-membrane anti-sigma factor of the extracytoplasmic-function sigma factor AlgU (AlgT, sigma-22) of Pseudomonas aeruginosa, encoded in the algU-mucABCD operon. It spans the cytoplasmic membrane once: its cytoplasmic N-terminal domain (RseA_N) binds AlgU and holds it away from its promoters, and its periplasmic C-terminal domain (RseA_C) binds the periplasmic protein MucB, which protects MucA from cleavage. Cell wall stress activates the site-1 protease AlgW (a DegS homologue) to cleave the periplasmic domain of MucA, after which an RseP homologue (YaeL) cleaves it within the membrane, releasing AlgU to transcribe its regulon, including the alginate biosynthesis operon. Loss-of-function mutations in mucA, frequent in cystic fibrosis isolates, derepress AlgU and convert the bacterium to the mucoid, alginate-overproducing form.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:19226327 Use of cell wall stress to characterize sigma 22 (AlgT/U) ac... | REMOVE | Summary: IPI with MucB (P38108), which binds the periplasmic domain of MucA in the sigma-sequestration complex. Reason: Bare protein binding is uninformative. MucA is the anti-sigma factor; MucB binding protects MucA from cleavage, and no more specific MF term describes MucA's side of that interaction. Removal does not mean the interaction is false. Supporting Evidence: PMID:19226327 Here we showed that MucB, encoded by the algT-mucABCD operon, interacts with MucA in the sigma-sequestration complex. |
| GO:0005515 protein binding | IPI PMID:19298369 Control of Pseudomonas aeruginosa AlgW protease cleavage of ... | REMOVE | Summary: IPI with MucB (P38108) from purified-protein binding assays. Reason: Bare protein binding is uninformative; the interaction (MucB binds MucA and blocks AlgW cleavage) is real but has no informative MF term on the MucA side. Supporting Evidence: PMID:19298369 We demonstrate that tight binding of MucB to MucA strongly inhibits this cleavage. |
| GO:0005515 protein binding | IPI PMID:19298369 Control of Pseudomonas aeruginosa AlgW protease cleavage of ... | REMOVE | Summary: IPI with the protease AlgW (Q9HVX1), for which MucA is the substrate. Reason: Bare protein binding is uninformative; being bound and cleaved by a protease is a substrate relationship, not a function of MucA. Supporting Evidence: PMID:19298369 Here we show that specific peptides bind to the periplasmic AlgW protease and activate its cleavage of MucA. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (cell membrane, single-pass). MucA has one predicted helix (89-105) between the cytoplasmic AlgU-binding domain and the periplasmic MucB-binding domain, and is described as a transmembrane protein. Reason: Inner (cytoplasmic) membrane location is supported by the topology and the published description, and is where the protein acts. Supporting Evidence: PMID:19298369 The alginate response is regulated by proteolytic cleavage of MucA, a transmembrane protein that inhibits the transcription factor AlgU, and by the periplasmic protein MucB. |
| GO:0016989 sigma factor antagonist activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN002211401, seeded by E. coli RseA (P0AFX7, EcoCyc IMP PMID:9159522) and by MucA itself. The node covers the RseA anti-sigma-E family of gammaproteobacteria (Yersinia, Haemophilus, Shewanella, Xanthomonas, Salmonella, Vibrio). Reason: Core function, also shown directly for MucA. The self-seed reflects MucA's own experimental evidence and is expected. Supporting Evidence: PMID:8759866 MucA was shown to act as an anti-sigma factor by binding to AlgU and inhibiting its activity. |
| GO:0016989 sigma factor antagonist activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from the RseA N-terminal (sigma-binding) domain. Reason: Consistent with the direct evidence and the family membership. Supporting Evidence: PMID:8759866 MucA was shown to act as an anti-sigma factor by binding to AlgU and inhibiting its activity. |
| GO:0016989 sigma factor antagonist activity | IMP PMID:22842599 Different mutations in mucA gene of Pseudomonas aeruginosa m... | ACCEPT | Summary: PseudoCAP IMP and a seed of the PTN002211401 IBD. The paper sequenced mucA in cystic fibrosis isolates and related truncating mutations to algU expression, a derepression phenotype. Reason: Core function. The seed paper gives the mutant-derepression evidence typical for an anti-sigma factor; direct binding and inhibition is reported in PMID:8759866. Seed verdict SOUND. Supporting Evidence: PMID:22842599 Mutations in mucA gene determine alginate operon overexpression and exopolysaccharide overproduction. PMID:8759866 MucA was shown to act as an anti-sigma factor by binding to AlgU and inhibiting its activity. |
| GO:0032885 regulation of polysaccharide biosynthetic process | IMP PMID:8759866 Control of AlgU, a member of the sigma E-like family of stre... | KEEP AS NON CORE | Summary: MucA holds AlgU inactive, and AlgU drives transcription of the alginate biosynthesis operon; mucA mutation causes alginate overproduction (mucoidy). Reason: True downstream regulatory consequence of the anti-sigma activity; GO has no negative-regulation child of this term, so it is as precise as available. Non-core relative to the molecular function, and matches the GO:0032885 accepted on algU. Supporting Evidence: PMID:8759866 Mutations that cause conversion to mucoidy in cystic fibrosis isolates occur frequently in mucA PMID:19226327 MucA sequesters extracytoplasmic function (ECF) sigma(22) (algT/U encoded) from target promoters including PalgD for alginate biosynthesis. |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000108 | MODIFY | Summary: Logical inference from sigma factor antagonist activity. Sequestering AlgU prevents it from directing RNA polymerase to its promoters. Reason: Correct but general. GO:2000143 negative regulation of DNA-templated transcription initiation (is_a GO:0045892) is the precise process for an anti-sigma factor, as on the fpvR, PA0471 and foxR reviews, and matches the GO:2000142 accepted on algU. Proposed replacements: negative regulation of DNA-templated transcription initiation Supporting Evidence: PMID:19226327 MucA sequesters extracytoplasmic function (ECF) sigma(22) (algT/U encoded) from target promoters including PalgD for alginate biosynthesis. |
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