| Annotation aspect | Evidence / finding | Interpretation for UniProt C5B1I2 (MexAM1_META1p4130, putative mluR) | Evidence source (citation id) |
|---|---|---|---|
| Identity verification status | No direct literature mapping found in retrieved sources for the symbol **mluR**, locus **MexAM1_META1p4130/META1p4130**, or direct experimental characterization of **UniProt C5B1I2** in *Methylorubrum extorquens* AM1. | The symbol is ambiguous/under-cited; functional annotation should therefore be based on the UniProt assignment and conserved FecR-family architecture/mechanism, while avoiding conflation with unrelated genes of similar name. | (pqac-00000000, pqac-00000001) |
| UniProt-provided identity | UniProt identifies C5B1I2 as **FecR, iron siderophore sensor protein** from *Methylorubrum extorquens* AM1, locus **MexAM1_META1p4130**, with domains **IPR006860 FecR**, **IPR032623 FecR_N**, **IPR012373 Ferrdict_sens_TM**, **PF16220 DUF4880**, **PF04773 FecR**. | The domain set is consistent with a **FecR-like anti-σ/pro-σ transducer** that links an outer-membrane TonB-dependent receptor signal to cytoplasmic transcriptional control of iron uptake genes. | (pqac-00000001, pqac-00000009) |
| Canonical protein class | FecR-like proteins are membrane-embedded regulatory proteins in TonB-dependent cell-surface signaling (CSS) systems, working with an outer-membrane receptor (e.g., FecA) and an ECF σ factor (e.g., FecI). | C5B1I2 is best interpreted as the **inner-membrane signaling/anti-σ component** of a CSS pathway, not as an enzyme or transporter. | (pqac-00000001, pqac-00000009, pqac-00000018) |
| Inferred cellular localization / topology | Archetypal FecR has an **N-proximal cytoplasmic region**, a **single transmembrane helix** near residues **~85–100** (prediction centered around ~82–100), and a **C-proximal periplasmic domain** that contacts the receptor signaling domain. | For C5B1I2, the most likely topology is **cytoplasmic N-terminus → single inner-membrane TM → periplasmic C-terminus**. | (pqac-00000012, pqac-00000015) |
| Periplasmic interaction partner | In the Fec archetype, the outer-membrane receptor signaling domain (FecA residues **1–79**) binds the periplasmic domain of FecR (residues **101–317**); related PupB:PupR proteins form a stable **1:1** periplasmic signaling complex. | C5B1I2 is predicted to receive signal from a **TonB-dependent outer-membrane transducer/receptor** via its periplasmic C-terminal region. | (pqac-00000012, pqac-00000014) |
| Cytoplasmic output function | The FecR N-terminus directly stimulates the partner ECF σ factor; induction-competent region maps to about residues **1–59** (or **9–59**) in the model system, and short N-terminal fragments can be sufficient for activation. | C5B1I2 likely functions by **controlling an ECF σ factor in the cytoplasm**, rather than binding DNA directly. | (pqac-00000015, pqac-00000007) |
| Pathway role | Canonical pathway: **TonB-dependent receptor ligand binding → conformational signaling across the envelope → FecR-like anti-σ processing → ECF σ activation → transcription of iron uptake genes**. Fur commonly represses these systems under iron sufficiency. | C5B1I2 is most plausibly part of an **iron-responsive transcriptional signaling pathway** for uptake functions, likely downstream of a TonB-dependent receptor and upstream of iron acquisition gene expression. | (pqac-00000001, pqac-00000009, pqac-00000017) |
| Proteolytic activation mechanism | FecR-like proteins undergo regulated intramembrane proteolysis: periplasmic cleavage(s) generate intermediates, then **RseP** cleaves within/near the membrane to release an N-terminal activating fragment. **Prc** acts upstream in the periplasm; newer CSS work also implicates **CtpA** in some systems. | C5B1I2 is expected to be a **proteolytically activated transducer**, not a static scaffold. | (pqac-00000011, pqac-00000013, pqac-00000006, pqac-00000002) |
| Fragment sizes / processing statistics | Reported FecR-related fragments include approximately **20 kDa**, **15 kDa**, and **12 kDa** products; additional species around **25 kDa** and **17 kDa** are described in related analyses, with **FecR85** comigrating near the 15-kDa form. | These fragment sizes provide a benchmark for interpreting any future immunoblot/proteolysis experiments on C5B1I2. | (pqac-00000011, pqac-00000012, pqac-00000013, pqac-00000007) |
| Key functional residues in activating N-terminus | In E. coli FecR, mutations **L13Q, W19R, W39R, W50R** in the N-terminal activating region abolish induction, and these residues are conserved in FecR-like proteins. | Conserved N-terminal residues in C5B1I2 would be strong candidates for σ-factor interaction and activation. | (pqac-00000015) |
| Quantitative regulatory data | Unrepressed **FecI abundance is <1 molecule/cell** in the model system; in an **rseP** mutant, **fecA-lacZ** is not induced by ferric citrate, whereas wild type shows about **10-fold induction**. | These values indicate that FecR/RseP-dependent signaling can strongly gate transcription and that σ-factor abundance is normally extremely low. | (pqac-00000012, pqac-00000011) |
| Recent 2024 mechanistic update | In the Fox CSS system, the receptor signaling domain can bind the anti-σ factor **before** induction and **protect it from proteolysis**; this revises the older view that receptor–anti-σ contact occurs only after ligand detection. | For C5B1I2, the resting state may involve a **preformed protected receptor–anti-σ complex** rather than a purely signal-triggered first contact. | (pqac-00000002, pqac-00000004) |
| Residue-level interface data from 2024 | AlphaFold-guided and mutational analysis in FoxA/FoxR identified a **5-stranded β-sheet interface**; **FoxR S292/G293** and **FoxA S81** are critical for interaction, while β-strand-disrupting substitutions abolish binding. | Although from a different bacterium, these data support a conserved **structured periplasmic receptor–anti-σ interface** relevant to C5B1I2 domain-function inference. | (pqac-00000003, pqac-00000016, pqac-00000020) |
| Receptor processing benchmark | In the Fox system, Western blots show full-length **FoxA ~84–85 kDa** and a processed form lacking the signaling domain at **~73–74 kDa**. | These data reinforce that CSS regulation can involve **processing of both the anti-σ protein and the receptor**, which may be relevant when interpreting future C5B1I2-associated receptor studies. | (pqac-00000016, pqac-00000019) |
| Methylorubrum-specific context | *M. extorquens* AM1 has documented **TonB-dependent metal uptake** systems (e.g., lanthanide uptake via **LutH** and a TonB-ABC pathway), but retrieved sources did **not** directly connect these methylotroph studies to a named **FecR/FecI-like iron CSS module** or to **mluR/C5B1I2**. | The organism clearly uses TonB-dependent metal acquisition, making a FecR-like iron signaling protein biologically plausible, but **direct experimental evidence for C5B1I2 remains absent in retrieved literature**. | (pqac-00000010) |


*Table: This table consolidates the strongest available evidence for annotating UniProt C5B1I2 as a FecR-like inner-membrane anti-sigma/sensor protein in Methylorubrum extorquens AM1. It distinguishes direct evidence from inference, highlights the ambiguity around the symbol mluR, and maps each claim to citation-ready context IDs.*