| Entity | Organism / system | Identity / partners | Functional interpretation | Inputs / signals discussed | Regulated outputs / phenotype | Quantitative or mechanistic details | Source (year) | DOI / URL | Evidence |
|---|---|---|---|---|---|---|---|---|---|
| **mxcQ / MxcQ (UniProt C5ASP2)** | *Methylorubrum extorquens* AM1 (formerly *Methylobacterium extorquens* AM1) | Target protein is encoded by **mxcQ**; part of the **MxcQE** two-component system, with **MxcE** as cognate response regulator; acts in the same regulatory network as **MxbDM** and **MxaB** for methanol oxidation gene control | Best-supported role in the literature is a **regulatory sensor histidine kinase involved in methanol dehydrogenase gene regulation**, not a directly characterized oxygen sensor in AM1 | Inputs are **not directly demonstrated** for AM1 MxcQ; literature discusses lanthanide availability and proposes **apo-XoxF** in the periplasm may interact with **MxcQ and/or MxbD** as part of the Ln-switch | Required within the regulatory cascade controlling **mxa** expression; network also influences **xox1** repression/activation depending on lanthanides | Direct biochemical sensing mechanism for AM1 MxcQ remains unresolved in cited literature | Vu et al. (2016); Pastawan et al. (2020) | https://doi.org/10.1128/JB.00937-15 ; https://doi.org/10.7831/ras.8.0_186 | (pqac-00000009, pqac-00000010, pqac-00000013) |
| **MxcQE pathway position** | *M. extorquens* AM1 | **MxcQE regulates expression of mxbDM**; **MxbDM directly regulates the mxa cluster**; response regulators **MxcE, MxaB, and MxbM** are required for activation of the **mxa** cluster, while **MxbM** is specifically required for repression of **xox1** | Places MxcQ upstream in the methanol/lanthanide regulatory hierarchy | Methanol oxidation state and lanthanide-dependent switching are the physiological context | **mxa cluster activation** under no-Ln conditions; **xox1 repression** under no-Ln conditions through the broader network | This is a regulatory model synthesized from genetics rather than direct MxcQ biochemistry | Pastawan et al. (2020) | https://doi.org/10.7831/ras.8.0_186 | (pqac-00000013, pqac-00000008) |
| **Ln-switch model involving MxcQ** | *M. extorquens* AM1 | MxcQ is one of the sensor kinases proposed to receive information from **apo-XoxF**; MxbD may play an analogous or complementary role | **Inferred sensor role** in lanthanide-responsive switching between Ca-dependent and Ln-dependent methanol dehydrogenases | Proposed signal is **apo-XoxF in the periplasm in the absence of lanthanides**; when Ln is present, active Ln-bound XoxF no longer signals through the same route | In the model, no-Ln conditions activate **mxa** and repress **xox1** via **MxcQE/MxbDM**; Ln presence causes **mxa repression** and **xox1 activation** | Model is explicitly presented as a hypothesis/postulate, not a direct mechanistic demonstration for MxcQ | Vu et al. (2016); Pastawan et al. (2020) | https://doi.org/10.1128/JB.00937-15 ; https://doi.org/10.7831/ras.8.0_186 | (pqac-00000010, pqac-00000013) |
| **Lanthanide sensitivity of the regulatory system** | *M. extorquens* AM1 | Reporter assays for **mxa** and **xox1** promoters demonstrate active response to lanthanides in the same network in which MxcQE functions | Supports that MxcQ participates in a highly lanthanide-sensitive regulatory system, even though the exact sensory ligand for MxcQ is unproven | La, Ce, Pr, Nd are effective signals in vivo at the system level | Differential transcription from **mxa** and **xox1** promoters | **Maximum growth rate and yield at ≥1 μM La**; **growth detectable at 2.5 nM La**; **intermediate expression from both mxa and xox1 at 50–100 nM La** | Vu et al. (2016) | https://doi.org/10.1128/JB.00937-15 | (pqac-00000014, pqac-00000016) |
| **Methanol oxidation phenotypes relevant to MxcQ-controlled network** | *M. extorquens* AM1 | MxcQ is not assayed directly here, but the phenotypes define the physiological output of the regulatory network that controls methanol dehydrogenases | The organism preferentially deploys Ln-dependent methanol oxidation when lanthanides are available | Methanol plus Ca and/or Ln | Growth on methanol via MxaFI, XoxF, and at least one additional Ln-dependent oxidation route | With 20 μM La: **wild type TD = 5.5 ± 0.2 h**; **xoxF1 mutant TD = 8.6 ± 0.9 h**; **xoxF1 xoxF2 TD = 19.1 ± 0.8 h**; triple MeDH mutant retained residual activity **9 ± 1 nmol·min⁻¹·mg⁻¹** | Vu et al. (2016) | https://doi.org/10.1128/JB.00937-15 | (pqac-00000016) |
| **AM1 MxcQ used in heterologous biosensor engineering** | Recombinant *E. coli* using AM1 MxcQ sensor domain | MxcQ sensor region from AM1 was fused to the **EnvZ** transmitter domain to create **MxcQZ AM1**; authors describe the imported region as a **methanol-sensing domain** | Suggests MxcQ contains a transferable sensory module responsive to methanol-related input, but this is an engineering inference rather than native mechanistic proof | Exogenous methanol in engineered *E. coli* | Activation of **OmpR/ompC** and GFP reporter in the chimera | Max fluorescence reported at **0.01% methanol** for **MxcQZ AM1**; chimeric junction placed near **EnvZ residue 254** in their model | Selvamani et al. (2020) | https://doi.org/10.4014/mbl.1908.08009 | (pqac-00000012, pqac-00000011) |
| **Related evidence from other methylotrophs** | *Methylobacterium aquaticum* strain 22A; *Methylobacillus flagellatus* | **mxcQE** is necessary for **MxaF-dependent methanol growth** in strain 22A; in *M. flagellatus*, proteins homologous to **MxcQ/MxcE** were identified, with only the histidine kinase domains matching for the MxcQ-like protein | Supports a conserved methylotrophy-regulatory role for MxcQ/MxcE-like systems across methylotrophs | Lanthanides and methanol metabolism | Control of methanol dehydrogenase expression / Ln response | In 22A, **PmxcQ** expression was constant in wild type but became **La-dependently decreasing in ΔlanM**; in *M. flagellatus*, the MxcQ-homologous histidine kinase showed partial homology limited to HK domains | Fujitani et al. (2022); Hemmann et al. (2023) | https://doi.org/10.3389/fmicb.2022.921636 ; https://doi.org/10.1016/j.jbc.2023.102940 | (pqac-00000002, pqac-00000006) |
| **Why UniProt may annotate C5ASP2 as NreB-like** | Annotation / domain-comparison issue | UniProt labels C5ASP2 as **oxygen sensor histidine kinase NreB / nitrogen regulation protein B**, while InterPro domains indicate a **generic histidine kinase architecture** (including HAMP/HATPase-related modules) consistent with broad HK family membership | The available AM1 literature more strongly supports **MxcQ as a methanol/lanthanide regulatory sensor kinase** than a proven NreB-type oxygen sensor; thus the NreB label is best treated as **homology-based annotation**, not organism-specific experimental proof | Likely based on sequence/domain similarity to histidine kinases rather than direct AM1 characterization | None directly shown for nitrate respiration in AM1 target literature | No cited AM1 paper demonstrates Fe–S-based oxygen sensing, nitrate-respiration control, or NreABC-like biochemistry for C5ASP2 | Comparison across cited AM1 and NreB literature | UniProt accession provided by user; comparison supported by cited literature below | (pqac-00000009, pqac-00000010, pqac-00000017, pqac-00000020, pqac-00000022) |
| **Canonical NreB for comparison** | *Staphylococcus carnosus* / staphylococcal NreABC system | **NreB** is a **cytosolic HisKA_3-type histidine kinase** paired with response regulator **NreC** and nitrate sensor **NreA** | Established **oxygen/redox sensor** controlling anaerobic nitrate respiration genes | O2 via an **O2-labile [4Fe-4S] cluster** in/associated with a PAS-like sensor region; nitrate via **NreA**, which inhibits NreB when nitrate is absent | Controls **narGHJI, nirRBD, sirAB, narT** and other genes for nitrate/nitrite reduction and fermentation | Under anaerobic conditions NreB is activated by a **[4Fe-4S]²⁺ cluster**; autophosphorylates at **H159** and transfers phosphate to **NreC D53**; NreA binding inhibits kinase activity without nitrate | Nilkens (2013); Price et al. (2021); Hsueh et al. citing Kamps/Müllner; Barth et al. (2018) | https://doi.org/10.1111/mmi.14795 ; https://doi.org/10.1128/jb.00687-13 ; https://doi.org/10.1111/1462-2920.14411 | (pqac-00000017, pqac-00000018, pqac-00000020, pqac-00000021, pqac-00000022) |
| **NreB mechanism vs. AM1 MxcQ** | Cross-system comparison | NreB has direct biochemical evidence for **Fe–S-dependent oxygen sensing** and nitrate-respiration regulation; AM1 MxcQ has genetic/physiological evidence for **methanol dehydrogenase regulation** in the Ln switch | Distinguishes a **validated NreB oxygen sensor** from an **MxcQ-like methylotrophy regulator** | NreB: O2 and nitrate; MxcQ: lanthanides, methanol-state, possibly apo-XoxF | NreB: respiratory nitrate genes; MxcQ: **mxa/xox1** methanol oxidation programs | This contrast is the key reason to treat the UniProt NreB name for C5ASP2 cautiously pending direct biochemical validation in AM1 | Comparative synthesis of all above | URLs above | (pqac-00000010, pqac-00000013, pqac-00000017, pqac-00000018, pqac-00000022) |


*Table: This table compiles the strongest literature-based evidence for the identity and function of MxcQ/C5ASP2 in Methylorubrum extorquens AM1 and contrasts it with canonical NreB oxygen sensors. It is useful for separating experimentally supported methylotrophy-related roles from broader homology-based histidine kinase annotations.*