| Year | System/organism | Key finding | Why it matters for annotating *M. extorquens* AM1 mluR (C5B1I2) | Publication (with URL) | Evidence source (pqac id) |
|---|---|---|---|---|---|
| 2024 | Fox cell-surface signaling system, *Pseudomonas aeruginosa* | The TonB-dependent transducer signaling domain (FoxA SD) binds the anti-σ factor FoxR **before** induction and protects it from proteolysis; this revises the classical model in which receptor–anti-σ contact was thought to occur mainly after ligand sensing. | Suggests C5B1I2, if truly FecR-like, may exist in a preformed receptor-bound resting complex rather than acting only after siderophore/iron signal arrival. This supports annotation as a regulated signaling transducer, not merely a passive anti-σ factor. | Wettstadt et al. 2024, *PLOS Biology* (published Dec 2024). https://doi.org/10.1371/journal.pbio.3002920 | (pqac-00000002, pqac-00000004) |
| 2024 | Fox/FoxR interface, *Pseudomonas aeruginosa* | AlphaFold-guided and mutational analysis identified a structured **5-stranded β-sheet interface** between the receptor signaling domain and anti-σ factor; residues FoxR S292/G293 and FoxA S81 are critical for interaction. | Strengthens inference that the periplasmic domain of C5B1I2 should mediate specific receptor coupling through an ordered interface, consistent with UniProt/IPR assignment to the FecR family. | Wettstadt et al. 2024, *PLOS Biology* (published Dec 2024). https://doi.org/10.1371/journal.pbio.3002920 | (pqac-00000003, pqac-00000016, pqac-00000020) |
| 2024 | Fox CSS proteolysis, *Pseudomonas aeruginosa* | Periplasmic proteases Prc and CtpA differentially control anti-σ factor turnover: Δprc stabilizes FoxR C-terminal fragments, whereas ΔctpA lowers FoxR C-terminal abundance; FoxA itself is also proteolytically processed. | Indicates that annotation of C5B1I2 should include likely participation in a multi-step proteolytic control pathway, potentially involving both anti-σ processing and receptor processing. | Wettstadt et al. 2024, *PLOS Biology* (published Dec 2024). https://doi.org/10.1371/journal.pbio.3002920 | (pqac-00000002, pqac-00000003, pqac-00000016, pqac-00000019) |
| 2023 | RseP intramembrane proteolysis, *Escherichia coli* | RseP, an S2P-family intramembrane protease, is confirmed as a protease that cleaves FecR-type membrane substrates; recent structural work highlights tandem PDZ domains as a size-exclusion filter and a membrane-reentrant β-sheet that helps discriminate substrates. | Supports a mechanistic annotation for C5B1I2 as a likely substrate of regulated intramembrane proteolysis after prior periplasmic trimming, a hallmark of FecR-family signaling proteins. | Yokoyama et al. 2023, *mBio* (published Jul 2023). https://doi.org/10.1128/mbio.01086-23 | (pqac-00000006) |
| 2023 | TonB-dependent outer-membrane transport/signaling review, mainly Gram-negative bacteria | Updated review of TonB/ExbB/ExbD energization emphasizes that conformational changes in TonB-dependent receptors can alter interactions with periplasmic anti-σ partners and thereby affect transcriptional signaling. | Reinforces that a FecR annotation for C5B1I2 implies coupling to a TonB-dependent outer-membrane receptor and envelope-spanning signal transduction rather than transport or catalysis by C5B1I2 itself. | Braun et al. 2023, *Journal of Bacteriology* (published Jun 2023). https://doi.org/10.1128/jb.00035-23 | (pqac-00000002) |
| 2022 (background) | Canonical Fec system, mainly *E. coli* and related Gram-negative bacteria | FecR-like proteins are inner-membrane anti-/pro-σ factors with cytoplasmic N-termini, a single transmembrane helix around residues ~85–100, and periplasmic C-termini that receive receptor signals; activation proceeds through sequential cleavage yielding ~20, 15, and 12 kDa fragments, with RseP acting late in the cascade. | This remains the best-supported mechanistic template for annotating C5B1I2 in the absence of direct AM1 experiments: a membrane-anchored FecR-like sensor transmitting iron uptake signals to an ECF σ factor. | Braun et al. 2022, *FEMS Microbiology Reviews* (published Feb 2022). https://doi.org/10.1093/femsre/fuac010 | (pqac-00000005, pqac-00000007, pqac-00000011, pqac-00000012) |


*Table: This table summarizes the most relevant 2023–2024 advances in FecR-like anti-sigma factor biology and regulated intramembrane proteolysis. It helps anchor the annotation of *Methylorubrum extorquens* AM1 C5B1I2 in current mechanistic understanding while clearly separating direct evidence from inference.*