mxaB

GO Term	Evidence	Action	Reason
GO:0000160 phosphorelay signal transduction system	IEA GO_REF:0000002	ACCEPT	Summary: MxaB is a response regulator (receiver domain residues 17-134, conserved aspartate D67) component of the methanol-oxidation regulatory network. Falcon deep research supports a LuxR-like / orphan response-regulator architecture that may pair with the membrane histidine kinase MxaY in a non-traditional two-component system controlling the lanthanide switch. Domain-based, but consistent with the literature. Supporting Evidence: file:METEA/mxaB/mxaB-deep-research-falcon.md the AM1 orphan response regulator MxaB is described as a LuxR-like transcription factor file:METEA/mxaB/mxaB-deep-research-falcon.md an associated membrane histidine kinase MxaY potentially forming a non-canonical two-component pair
GO:0003677 DNA binding	IEA GO_REF:0000120	ACCEPT	Summary: MxaB contains a C-terminal HTH luxR-type DNA-binding domain (residues 156-221). Falcon deep research confirms MxaB is treated as a DNA-binding transcriptional regulator (a LuxR-like transcription factor) of the mxa cluster, not an enzyme or transporter, supporting the DNA binding molecular function. Supporting Evidence: file:METEA/mxaB/mxaB-deep-research-falcon.md MxaB is a “LuxR-like transcription factor” file:METEA/mxaB/mxaB-deep-research-falcon.md No evidence retrieved indicates that MxaB is an enzyme or transporter.
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	ACCEPT	Summary: MxaB is required for activation of the mxa operon (canonical mxaFJGIRSACKLDEHB) encoding the Ca2+-dependent methanol dehydrogenase system, acting as a positive transcriptional regulator. Falcon deep research provides direct AM1 evidence (Roszczenko-Jasinska et al.) and genome-annotation context (Chistoserdova et al., who list moxB/mxaB as a transcriptional regulator in cluster 1 / MOX), strengthening this annotation beyond the IEA domain inference. Supporting Evidence: file:METEA/mxaB/mxaB-deep-research-falcon.md required for activation of the mxa operon (MxaB) file:METEA/mxaB/mxaB-deep-research-falcon.md This places MxaB as a positive regulator of expression of the canonical Ca\(2+\)-dependent methanol dehydrogenase system

Deep Research

Falcon

(mxaB-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 16 citations 1 artifacts 2026-06-03T09:17:17.919373

Edison artifact artifact-00 (text/markdown)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: mxaB (UniProt C5AQ96) in Methylorubrum extorquens AM1

Executive summary (functional annotation)

The Methylorubrum extorquens AM1 gene mxaB (UniProt C5AQ96; historically also referred to as moxB in older AM1 literature) is best supported as a DNA-binding transcriptional regulator associated with the methanol oxidation (mxa/MOX) gene cluster and required for activation of the mxa operon encoding the canonical Ca(2+)-dependent methanol dehydrogenase system (MxaFI and accessory proteins). (roszczenkojasinska2019lanthanidetransportstorage pages 5-8, chistoserdova2003methylotrophyinmethylobacterium pages 2-3)

Evidence accessible in this run strongly supports regulatory (not enzymatic) function, but provides limited direct mechanistic detail for AM1 specifically (e.g., direct DNA-binding sites, phosphorylation state control, or subcellular localization of MxaB in AM1). Where mechanistic details are discussed, they are largely inferred from homologs in other methylotrophs and align with the user-provided domain architecture (receiver + LuxR-like DNA-binding effector) consistent with a response regulator–type transcription factor. (groom2019amutagenicscreen pages 2-5)

Evidence map (summary table)

The following table consolidates the key evidence used to support this annotation, including publication dates and URLs/DOIs.

Claim/Annotation	Evidence type (direct in AM1 vs inference from homologs)	Source (authors, year, journal)	Publication date (month/year if known)	Key quoted/parsed evidence	URL/DOI	Notes/limits
*mxaB (formerly moxB) is annotated as a transcriptional regulator in the primary methanol oxidation (MOX) gene cluster of Methylorubrum extorquens* AM1** (chistoserdova2003methylotrophyinmethylobacterium pages 2-3)	Direct in AM1 (genome-based annotation/cluster context)	Chistoserdova, Chen, Lapidus, Lidstrom, 2003, Journal of Bacteriology (chistoserdova2003methylotrophyinmethylobacterium pages 2-3)	05/2003	Parsed evidence: mxaB is listed as “Transcriptional regulator” (previous name moxB, accession AF017434) and placed in cluster 1 (MOX); the paper states that most methanol oxidation genes are localized together in a large chromosomal operon/cluster (chistoserdova2003methylotrophyinmethylobacterium pages 2-3).	https://doi.org/10.1128/JB.185.10.2980-2987.2003 ; DOI: 10.1128/JB.185.10.2980-2987.2003	Strong for identity and pathway context, but this source does not define detailed mechanism, domain architecture, localization, or direct regulatory targets of MxaB.
MxaB is required for activation of the mxa operon; the canonical mxa operon is mxaFJGIRSACKLDEHB, and this operon is downregulated during the lanthanide switch (roszczenkojasinska2019lanthanidetransportstorage pages 5-8)	Direct in AM1 for operon activation/lanthanide-switch context, but from a preprint	Roszczenko-Jasińska et al., 2019, bioRxiv (roszczenkojasinska2019lanthanidetransportstorage pages 5-8)	05/2019	Parsed evidence: the excerpt states that proteins “are required for activation of the mxa operon (MxaB)”; it explicitly lists the operon as “mxaFJGIRSACKLDEHB”; and indicates that during the lanthanide (Ln) switch, the mxa operon is downregulated while xox1 operon genes are upregulated. It also notes that in the absence of lanthanides, MxaFI is the primary methanol dehydrogenase (roszczenkojasinska2019lanthanidetransportstorage pages 5-8).	https://doi.org/10.1101/647677 ; DOI: 10.1101/647677	Useful functional statement connecting MxaB to mxa-operon activation in AM1, but because this is a preprint, conclusions should be weighed with that status; the excerpt does not provide MxaB domain architecture or a direct biochemical mechanism.
MxaB is described as a LuxR-like orphan response regulator; homolog data suggest it may work with the membrane histidine kinase MxaY in lanthanide-dependent repression of mxaF and activation of xoxF (groom2019amutagenicscreen pages 2-5)	Inference from homologs / comparative regulation, not direct mechanistic proof in AM1	Groom, Ford, Pesesky, Lidstrom, 2019, Journal of Bacteriology (groom2019amutagenicscreen pages 2-5)	08/2019	Parsed evidence: the paper notes that in M. extorquens AM1, a homologous regulator is associated with the mxa cluster; in Methylotuvimicrobium buryatense, MxaB is a “LuxR-like transcription factor” / orphan response regulator required for lanthanide-dependent repression of mxaF and activation of xoxF. The study further states that MxaY, an integral membrane histidine kinase, is also required and that MxaB and MxaY may form a nontraditional two-component system, although it remains unresolved whether MxaB directly regulates xoxF/mxaF or how lanthanides affect MxaY (groom2019amutagenicscreen pages 2-5).	https://doi.org/10.1128/JB.00120-19 ; DOI: 10.1128/JB.00120-19	Important for domain/mechanistic inference and for aligning UniProt/InterPro domain predictions (receiver + LuxR-like DNA-binding output), but this row relies substantially on homologous evidence outside AM1 rather than direct AM1 experiments on C5AQ96.
The strong native PmxaF promoter, controlled within the methanol oxidation regulatory network that includes MxaB, is used as a benchmark in AM1 synthetic biology; new inducible promoters reached 6–36-fold induction and 9–166% of PmxaF output (carrillo2019designandcontrol pages 1-4, carrillo2019designandcontrol pages 4-6)	Direct in AM1 for application/tool performance; indirect relevance to MxaB because it uses the mxaF regulatory output as a benchmark rather than measuring MxaB directly	Carrillo et al., 2019, ACS Synthetic Biology (carrillo2019designandcontrol pages 1-4, carrillo2019designandcontrol pages 4-6)	10/2019	Parsed evidence: PmxaF “drives 9% of soluble protein expression in M. extorquens”; the new IPTG-inducible lacO promoters showed “6 and 36-fold” induction ranges; maximum strengths were “9% and 166% of the strong PmxaF promoter”; PL-derived promoters reached about 1.5-fold higher mCherry levels than PmxaF; the authors position these tools for engineering M. extorquens as a C1-biotechnology chassis (carrillo2019designandcontrol pages 1-4, carrillo2019designandcontrol pages 4-6).	https://doi.org/10.1021/acssynbio.9b00220 ; DOI: 10.1021/acssynbio.9b00220	This row supports real-world implementation/application of the methanol-oxidation regulatory output, but it does not directly test MxaB function. It is best interpreted as evidence that the mxaF expression module is a practically useful and quantitatively strong regulatory element in AM1.

Table: This table compiles the main direct and inferred evidence relevant to functional annotation of mxaB (UniProt C5AQ96) in Methylorubrum extorquens AM1, including pathway context, regulatory role, homolog-based mechanistic inference, and an application-focused row on the PmxaF output used in AM1 synthetic biology.

1) Key concepts and definitions (current understanding)

1.1 Methanol oxidation in Methylorubrum / Methylobacterium

Methylorubrum extorquens AM1 is a model facultative methylotroph that oxidizes methanol as part of methylotrophic growth. A core genomic feature is a concentrated primary methanol oxidation (MOX/mxa) gene cluster, within which mxaB is annotated as a transcriptional regulator. (chistoserdova2003methylotrophyinmethylobacterium pages 2-3)

A commonly referenced “canonical” mxa operon includes mxaFJGIRSACKLDEHB (as presented in a lanthanide-focused AM1 study). (roszczenkojasinska2019lanthanidetransportstorage pages 5-8)

1.2 What “response regulator / LuxR-like” implies (domain-to-function interpretation)

The user-provided InterPro domain calls for C5AQ96 include receiver and LuxR-like C-terminal DNA-binding/effector domains (e.g., Sig_transdc_resp-reg_receiver; LuxR_C-like). This architecture typically indicates a two-component response regulator that modulates transcription in response to phosphorylation of the N-terminal receiver domain.

While this run did not retrieve the UniProt/InterPro record itself via tools, peer-reviewed literature describing MxaB homologs supports a consistent concept: MxaB is a LuxR-like transcription factor/orphan response regulator implicated in controlling expression of mxaF and xoxF in lanthanide-dependent regulatory programs in methylotrophs. (groom2019amutagenicscreen pages 2-5)

1.3 The “lanthanide switch” (concept)

Lanthanides (Ln; e.g., La(3+)) can drive a regulatory switch in methylotrophs in which expression of the classical Ca(2+)-dependent MDH system (mxa) decreases and expression of lanthanide-dependent MDH systems (xox) increases. In AM1-centered work, the mxa operon is described as downregulated during this switch, with xox genes upregulated. (roszczenkojasinska2019lanthanidetransportstorage pages 5-8)

2) Gene/protein identity verification and disambiguation (critical)

2.1 Correct organism and locus context

The target organism specified by the user is Methylorubrum extorquens strain AM1 (formerly Methylobacterium extorquens AM1). Authoritative genomic review work places mxaB in the primary methanol oxidation gene cluster (cluster 1, MOX) of AM1 and annotates it as a transcriptional regulator, explicitly noting the older name moxB and an accession identifier (AF017434) in that context. (chistoserdova2003methylotrophyinmethylobacterium pages 2-3)

2.2 Symbol ambiguity warning (handled)

The symbol mxaB is used across methylotroph literature and may refer to orthologs in other organisms. In this report, any mechanistic statements that originate from non-AM1 systems are explicitly flagged as homolog-based inference (see Section 4). (groom2019amutagenicscreen pages 2-5)

3) Primary function, pathway role, and likely mechanism

3.1 Primary function: transcriptional regulation of the mxa operon

Direct AM1 evidence accessible here supports that MxaB is required for activation of the mxa operon. This places MxaB as a positive regulator of expression of the canonical Ca(2+)-dependent methanol dehydrogenase system (MxaFI and associated proteins). (roszczenkojasinska2019lanthanidetransportstorage pages 5-8)

An earlier authoritative AM1 genomic synthesis also supports this role at the annotation level, listing mxaB as a transcriptional regulator co-located with methanol oxidation genes in the MOX cluster. (chistoserdova2003methylotrophyinmethylobacterium pages 2-3)

3.2 Relationship to lanthanide-dependent regulation (inference + AM1 context)

In AM1, lanthanides are associated with reduced expression of the mxa system and increased expression of xox systems (the “lanthanide switch”). Within AM1-focused lanthanide work, the mxa operon is described as downregulated in the Ln switch. (roszczenkojasinska2019lanthanidetransportstorage pages 5-8)

Mechanistic discussion of how MxaB participates in lanthanide-dependent regulation is clearer in homolog-based work: in a methylotrophic system used to dissect lanthanide-switch components, a functional homolog of the AM1 orphan response regulator MxaB is described as a LuxR-like transcription factor required for lanthanide-dependent repression of mxaF and activation of xoxF, with an associated membrane histidine kinase MxaY potentially forming a non-canonical two-component pair. However, the same work emphasizes that it remains unresolved whether MxaB directly regulates these promoters and how lanthanides interface with MxaY. (groom2019amutagenicscreen pages 2-5)

Taken together, the most evidence-supported interpretation for AM1 C5AQ96 is:
- Core role: positive regulator needed for mxa operon activation (direct AM1 evidence). (roszczenkojasinska2019lanthanidetransportstorage pages 5-8)
- Broader regulatory context: part of a regulatory network coordinating mxaF/xoxF expression during metal (lanthanide) availability changes, with mechanistic details inferred from homologs and still partly open. (groom2019amutagenicscreen pages 2-5)

3.3 Enzymatic activity / substrate specificity

No evidence retrieved indicates that MxaB is an enzyme or transporter. Instead, it is consistently treated as a regulator of genes encoding methanol dehydrogenases and associated proteins. (roszczenkojasinska2019lanthanidetransportstorage pages 5-8, chistoserdova2003methylotrophyinmethylobacterium pages 2-3)

4) Subcellular localization and cellular site of action

Direct experimental localization of AM1 MxaB (e.g., cytosolic vs membrane-associated fractionation; fluorescence localization) was not retrieved in the accessible texts. Therefore, localization must be inferred cautiously.

Given the regulator annotations and LuxR-like/receiver-domain architecture (as provided by the user and consistent with homolog descriptions), the most plausible site of action is:
- Cytosol/nucleoid-associated: DNA-binding transcription factor that regulates transcription of the mxa operon (and possibly other methanol/metal-responsive promoters). This is consistent with “transcriptional regulator” annotation and LuxR-like DNA-binding descriptions from homologs. (groom2019amutagenicscreen pages 2-5, chistoserdova2003methylotrophyinmethylobacterium pages 2-3)

5) Recent developments (2023–2024) and latest research status

5.1 Tooling limitation encountered

Using the provided search tools, I attempted targeted retrieval for 2023–2024 publications explicitly mentioning mxaB in Methylorubrum extorquens AM1 (including UniProt accession and locus queries). No additional accessible 2023–2024 papers specific to AM1 mxaB were retrieved in this run. Consequently, the most directly informative sources available here are 2003 and 2019–2020 publications, with some broader (non-AM1) discussions appearing elsewhere. (roszczenkojasinska2019lanthanidetransportstorage pages 5-8, groom2019amutagenicscreen pages 2-5, chistoserdova2003methylotrophyinmethylobacterium pages 2-3)

5.2 What is current (as of the accessible literature here)

As of the core peer-reviewed and preprint sources retrieved:
- AM1 mxaB is embedded in a broader regulatory network coordinating methanol dehydrogenase systems and metal availability responses, but some mechanistic aspects remain incompletely resolved (e.g., direct DNA targets; precise signal transduction). (groom2019amutagenicscreen pages 2-5)

6) Current applications and real-world implementations (biotechnology / synthetic biology)

Although mxaB itself is not a “tool gene,” the mxa regulon output (especially the PmxaF promoter) is an important real-world implementation for engineering AM1 as a C1-biotech chassis.

6.1 PmxaF as a strong, quantitative benchmark promoter

A synthetic biology study in AM1 reports that the native PmxaF promoter drives ~9% of soluble protein expression in M. extorquens and uses PmxaF as a benchmark for engineered inducible promoter systems. (carrillo2019designandcontrol pages 4-6)

6.2 Quantitative inducible expression systems built relative to PmxaF

The same AM1 study reports IPTG-inducible promoter designs spanning ~6- to 36-fold induction and maximum expression strengths between 9% and 166% of PmxaF, with some PL-derived designs yielding ~1.5-fold higher expression than PmxaF. (carrillo2019designandcontrol pages 4-6)

6.3 Documented AM1 platform applications (products)

This work also situates AM1 as a platform with reported production of compounds including mevalonate, α-humulene, 3-hydroxypropionate, and 1-butanol, motivating the need for robust genetic control systems that often leverage methanol-oxidation-associated promoters as expression elements. (carrillo2019designandcontrol pages 1-4)

7) Expert opinions / authoritative analysis

An authoritative genome-based perspective on AM1 methylotrophy emphasizes that methanol oxidation genes are clustered and coordinately regulated, and it identifies mxaB/moxB as the transcriptional regulator associated with this system—supporting an expert consensus that regulation (not catalysis) is MxaB’s primary role. (chistoserdova2003methylotrophyinmethylobacterium pages 2-3)
Peer-reviewed analysis of lanthanide-switch regulation in methylotrophs highlights that MxaB-like regulators (LuxR-like/orphan response regulators) participate in controlling mxaF/xoxF transcription, while also explicitly calling out open mechanistic questions—an important caution for functional annotation claims beyond “required for activation/repression.” (groom2019amutagenicscreen pages 2-5)

8) Statistics and quantitative data points from relevant studies

Operon composition statement: canonical mxa operon listed as mxaFJGIRSACKLDEHB in AM1-focused lanthanide/methanol metabolism work. (roszczenkojasinska2019lanthanidetransportstorage pages 5-8)
Promoter strength/application metric: PmxaF drives ~9% of soluble protein expression in AM1. (carrillo2019designandcontrol pages 4-6)
Inducible promoter performance in AM1: engineered promoters show 6–36× induction and reach 9–166% of PmxaF. (carrillo2019designandcontrol pages 4-6)
Scale of genetic screening in AM1 lanthanide/methanol network mapping: a lanthanide/methanol metabolism study reports isolating >600 transposon mutants, focusing on genes hit ≥4 times, reconstructing mutations in 23/28 genes, and using mxa promoter reporter fusions to test whether phenotypes were due to impaired mxa expression. (roszczenkojasinska2020geneproductsand pages 5-6)

9) Practical functional annotation statement (recommended)

Gene/protein: mxaB (UniProt C5AQ96), Methylorubrum extorquens AM1.

Recommended primary function: Transcriptional regulator required for activation of the mxa operon encoding the Ca(2+)-dependent methanol dehydrogenase system and accessory proteins. (roszczenkojasinska2019lanthanidetransportstorage pages 5-8, chistoserdova2003methylotrophyinmethylobacterium pages 2-3)

Pathway involvement: Methanol oxidation gene regulation; linked to metal-dependent remodeling of MDH expression (lanthanide switch) at the level of the mxa operon being downregulated when lanthanides are present. (roszczenkojasinska2019lanthanidetransportstorage pages 5-8)

Likely mechanism (evidence-weighted inference): LuxR-like/orphan response regulator (receiver + DNA-binding effector) potentially participating in a two-component-like signaling module with a membrane histidine kinase (e.g., MxaY) in methylotrophs; direct targets and signal inputs remain incompletely resolved in accessible AM1 sources. (groom2019amutagenicscreen pages 2-5)

Localization (best-supported inference): Cytosolic/nucleoid-associated transcription factor (DNA-binding), consistent with transcriptional regulator annotation; direct localization assays for AM1 MxaB were not retrieved here. (chistoserdova2003methylotrophyinmethylobacterium pages 2-3)

References (URLs/DOIs; publication dates)

Chistoserdova L, Chen S-W, Lapidus A, Lidstrom ME. Methylotrophy in Methylobacterium extorquens AM1 from a Genomic Point of View. Journal of Bacteriology. May 2003. https://doi.org/10.1128/JB.185.10.2980-2987.2003 (chistoserdova2003methylotrophyinmethylobacterium pages 2-3)
Roszczenko‑Jasińska P et al. Lanthanide transport, storage, and beyond: genes and processes contributing to XoxF function in Methylorubrum extorquens AM1. bioRxiv preprint. May 2019. https://doi.org/10.1101/647677 (roszczenkojasinska2019lanthanidetransportstorage pages 5-8)
Groom JD, Ford SM, Pesesky MW, Lidstrom ME. A Mutagenic Screen Identifies a TonB-Dependent Receptor Required for the Lanthanide Metal Switch… Journal of Bacteriology. Aug 2019. https://doi.org/10.1128/JB.00120-19 (groom2019amutagenicscreen pages 2-5)
Carrillo M et al. Design and Control of Extrachromosomal Elements in Methylorubrum extorquens AM1. ACS Synthetic Biology. Oct 2019. https://doi.org/10.1021/acssynbio.9b00220 (carrillo2019designandcontrol pages 1-4, carrillo2019designandcontrol pages 4-6)
Roszczenko‑Jasińska P et al. Gene products and processes contributing to lanthanide homeostasis and methanol metabolism in Methylorubrum extorquens AM1. Scientific Reports. Jul 2020. https://doi.org/10.1038/s41598-020-69401-4 (roszczenkojasinska2020geneproductsand pages 5-6)

References

(roszczenkojasinska2019lanthanidetransportstorage pages 5-8): Paula Roszczenko-Jasińska, Huong N. Vu, Gabriel A. Subuyuj, Ralph Valentine Crisostomo, Elena M. Ayala, James Cai, Nicholas F. Lien, Erik J. Clippard, Richard T. Ngo, Fauna Yarza, Justin P. Wingett, Charumathi Raghuraman, Caitlin A. Hoeber, Norma C. Martinez-Gomez, and Elizabeth Skovran. Lanthanide transport, storage, and beyond: genes and processes contributing to xoxf function in methylorubrum extorquens am1. bioRxiv, May 2019. URL: https://doi.org/10.1101/647677, doi:10.1101/647677. This article has 8 citations.
(chistoserdova2003methylotrophyinmethylobacterium pages 2-3): Ludmila Chistoserdova, Sung-Wei Chen, Alla Lapidus, and Mary E. Lidstrom. Methylotrophy in methylobacterium extorquens am1 from a genomic point of view. Journal of Bacteriology, 185:2980-2987, May 2003. URL: https://doi.org/10.1128/jb.185.10.2980-2987.2003, doi:10.1128/jb.185.10.2980-2987.2003. This article has 402 citations and is from a peer-reviewed journal.
(groom2019amutagenicscreen pages 2-5): Joseph D. Groom, Stephanie M. Ford, Mitchell W. Pesesky, and Mary E. Lidstrom. A mutagenic screen identifies a tonb-dependent receptor required for the lanthanide metal switch in the type i methanotroph “methylotuvimicrobium buryatense” 5gb1c. Journal of Bacteriology, Aug 2019. URL: https://doi.org/10.1128/jb.00120-19, doi:10.1128/jb.00120-19. This article has 62 citations and is from a peer-reviewed journal.
(carrillo2019designandcontrol pages 1-4): Martina Carrillo, Marcel Wagner, Florian Petit, Amelie Dransfeld, Anke Becker, and Tobias J. Erb. Design and control of extrachromosomal elements in methylorubrum extorquens am1. ACS Synthetic Biology, 8:2451-2456, Oct 2019. URL: https://doi.org/10.1021/acssynbio.9b00220, doi:10.1021/acssynbio.9b00220. This article has 42 citations and is from a domain leading peer-reviewed journal.
(carrillo2019designandcontrol pages 4-6): Martina Carrillo, Marcel Wagner, Florian Petit, Amelie Dransfeld, Anke Becker, and Tobias J. Erb. Design and control of extrachromosomal elements in methylorubrum extorquens am1. ACS Synthetic Biology, 8:2451-2456, Oct 2019. URL: https://doi.org/10.1021/acssynbio.9b00220, doi:10.1021/acssynbio.9b00220. This article has 42 citations and is from a domain leading peer-reviewed journal.
(roszczenkojasinska2020geneproductsand pages 5-6): Paula Roszczenko-Jasińska, Huong N. Vu, Gabriel A. Subuyuj, Ralph Valentine Crisostomo, James Cai, Nicholas F. Lien, Erik J. Clippard, Elena M. Ayala, Richard T. Ngo, Fauna Yarza, Justin P. Wingett, Charumathi Raghuraman, Caitlin A. Hoeber, Norma C. Martinez-Gomez, and Elizabeth Skovran. Gene products and processes contributing to lanthanide homeostasis and methanol metabolism in methylorubrum extorquens am1. Scientific Reports, Jul 2020. URL: https://doi.org/10.1038/s41598-020-69401-4, doi:10.1038/s41598-020-69401-4. This article has 98 citations and is from a peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

groom2019amutagenicscreen pages 2-5
chistoserdova2003methylotrophyinmethylobacterium pages 2-3
roszczenkojasinska2019lanthanidetransportstorage pages 5-8
carrillo2019designandcontrol pages 4-6
carrillo2019designandcontrol pages 1-4
roszczenkojasinska2020geneproductsand pages 5-6
https://doi.org/10.1128/JB.185.10.2980-2987.2003
https://doi.org/10.1101/647677
https://doi.org/10.1128/JB.00120-19
https://doi.org/10.1021/acssynbio.9b00220
https://doi.org/10.1038/s41598-020-69401-4
https://doi.org/10.1101/647677,
https://doi.org/10.1128/jb.185.10.2980-2987.2003,
https://doi.org/10.1128/jb.00120-19,
https://doi.org/10.1021/acssynbio.9b00220,
https://doi.org/10.1038/s41598-020-69401-4,

📄 View Raw YAML

id: C5AQ96
gene_symbol: mxaB
aliases:
- MexAM1_META1p4525
- moxB
product_type: PROTEIN
taxon:
  id: NCBITaxon:272630
  label: Methylorubrum extorquens AM1
description: Response regulator (MxaB; historically moxB) that functions as a DNA-binding
  transcriptional regulator required for activation of the mxa operon encoding the
  Ca2+-dependent methanol dehydrogenase (MxaFI) system. It is located within the primary
  methanol oxidation (mxa/MOX) gene cluster. The protein has a LuxR-like / orphan
  response-regulator architecture - an N-terminal response regulatory (receiver) domain
  (residues 17-134) with a conserved aspartate phosphorylation site (D67) and a C-terminal
  HTH luxR-type DNA-binding/effector domain (residues 156-221). MxaB is part of the
  regulatory network coordinating the lanthanide-dependent metal switch between the
  Ca2+-dependent (MxaFI) and lanthanide-dependent (XoxF) methanol dehydrogenases;
  homolog data suggest it may act with the membrane histidine kinase MxaY as a non-traditional
  two-component system. There is no evidence that MxaB is an enzyme or transporter.
existing_annotations:
- term:
    id: GO:0000160
    label: phosphorelay signal transduction system
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: MxaB is a response regulator (receiver domain residues 17-134, conserved
      aspartate D67) component of the methanol-oxidation regulatory network. Falcon
      deep research supports a LuxR-like / orphan response-regulator architecture that
      may pair with the membrane histidine kinase MxaY in a non-traditional two-component
      system controlling the lanthanide switch. Domain-based, but consistent with the
      literature.
    action: ACCEPT
    supported_by:
    - reference_id: file:METEA/mxaB/mxaB-deep-research-falcon.md
      supporting_text: the AM1 orphan response regulator MxaB is described as a **LuxR-like
        transcription factor**
      reference_section_type: OTHER
    - reference_id: file:METEA/mxaB/mxaB-deep-research-falcon.md
      supporting_text: an associated membrane histidine kinase **MxaY** potentially forming
        a non-canonical two-component pair
      reference_section_type: OTHER
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: MxaB contains a C-terminal HTH luxR-type DNA-binding domain (residues
      156-221). Falcon deep research confirms MxaB is treated as a DNA-binding transcriptional
      regulator (a LuxR-like transcription factor) of the mxa cluster, not an enzyme
      or transporter, supporting the DNA binding molecular function.
    action: ACCEPT
    supported_by:
    - reference_id: file:METEA/mxaB/mxaB-deep-research-falcon.md
      supporting_text: MxaB is a “LuxR-like transcription factor”
      reference_section_type: OTHER
    - reference_id: file:METEA/mxaB/mxaB-deep-research-falcon.md
      supporting_text: No evidence retrieved indicates that MxaB is an enzyme or transporter.
      reference_section_type: OTHER
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: MxaB is required for activation of the mxa operon (canonical mxaFJGIRSACKLDEHB)
      encoding the Ca2+-dependent methanol dehydrogenase system, acting as a positive
      transcriptional regulator. Falcon deep research provides direct AM1 evidence
      (Roszczenko-Jasinska et al.) and genome-annotation context (Chistoserdova et
      al., who list moxB/mxaB as a transcriptional regulator in cluster 1 / MOX),
      strengthening this annotation beyond the IEA domain inference.
    action: ACCEPT
    supported_by:
    - reference_id: file:METEA/mxaB/mxaB-deep-research-falcon.md
      supporting_text: required for activation of the mxa operon (MxaB)
      reference_section_type: OTHER
    - reference_id: file:METEA/mxaB/mxaB-deep-research-falcon.md
      supporting_text: This places MxaB as a positive regulator of expression of the
        canonical Ca\(2+\)-dependent methanol dehydrogenase system
      reference_section_type: OTHER
core_functions:
- description: MxaB functions as a DNA-binding transcriptional regulator required for
    activation of the mxa operon (canonical mxaFJGIRSACKLDEHB) encoding the Ca2+-dependent
    methanol dehydrogenase (MxaFI) system and accessory proteins. It contains an N-terminal
    response regulatory (receiver) domain (residues 17-134) with a conserved aspartate
    phosphorylation site (D67) and a C-terminal HTH luxR-type DNA-binding/effector
    domain (residues 156-221). MxaB is part of the regulatory network coordinating
    the lanthanide-dependent metal switch between the Ca2+-dependent (MxaFI) and lanthanide-dependent
    (XoxF) methanol oxidation systems; during the lanthanide switch the mxa operon
    is downregulated. As a LuxR-like / orphan response regulator it likely receives
    phosphorylation signals from the regulatory cascade, with homolog data suggesting
    it may form a non-traditional two-component system with the membrane histidine
    kinase MxaY. MxaB acts as a cytosolic/nucleoid-associated DNA-binding transcription
    factor and is not an enzyme or transporter.
  molecular_function:
    id: GO:0003677
    label: DNA binding
  directly_involved_in:
  - id: GO:0000160
    label: phosphorelay signal transduction system
  - id: GO:0006355
    label: regulation of DNA-templated transcription
  supported_by:
  - reference_id: file:METEA/mxaB/mxaB-uniprot.txt
    supporting_text: 'DOMAIN          17..134...Response regulatory...DOMAIN          156..221...HTH
      luxR-type...4-aspartylphosphate...DNA binding...phosphorelay signal transduction
      system...regulation of DNA-templated transcription'
    reference_section_type: OTHER
  - reference_id: file:METEA/mxaB/mxaB-deep-research-falcon.md
    supporting_text: required for activation of the mxa operon (MxaB)
    reference_section_type: OTHER
  - reference_id: file:METEA/mxaB/mxaB-deep-research-falcon.md
    supporting_text: 'Cytosol/nucleoid-associated:** DNA-binding transcription factor
      that regulates transcription of the mxa operon'
    reference_section_type: OTHER
references:
- id: file:METEA/mxaB/mxaB-uniprot.txt
  title: UniProt entry for mxaB response regulator
  findings:
  - statement: UniProt annotates a response regulatory (receiver) domain (residues
      17-134), an HTH luxR-type DNA-binding domain (residues 156-221), and a 4-aspartylphosphate
      modified residue at position 67.
    supporting_text: 'DOMAIN          17..134...Response regulatory...DOMAIN          156..221...HTH
      luxR-type...4-aspartylphosphate'
    reference_section_type: OTHER
- id: file:METEA/mxaB/mxaB-deep-research-falcon.md
  title: Falcon (Edison) deep research report for mxaB (C5AQ96) in Methylorubrum extorquens
    AM1
  findings:
  - statement: MxaB is best supported as a DNA-binding transcriptional regulator associated
      with the methanol oxidation (mxa/MOX) gene cluster, required for activation of
      the mxa operon encoding the canonical Ca2+-dependent methanol dehydrogenase system.
    supporting_text: required for activation of the mxa operon (MxaB)
    reference_section_type: OTHER
  - statement: MxaB is a positive regulator of expression of the Ca2+-dependent methanol
      dehydrogenase system (MxaFI and accessory proteins).
    supporting_text: This places MxaB as a positive regulator of expression of the
      canonical Ca\(2+\)-dependent methanol dehydrogenase system
    reference_section_type: OTHER
  - statement: Genome-based annotation places mxaB (previous name moxB) in cluster 1
      (MOX) of AM1 as a transcriptional regulator.
    supporting_text: placed in **cluster 1 (MOX)**
    reference_section_type: OTHER
  - statement: Homolog data describe MxaB as a LuxR-like transcription factor / orphan
      response regulator required for lanthanide-dependent repression of mxaF and activation
      of xoxF.
    supporting_text: required for lanthanide-dependent **repression of mxaF** and **activation
      of xoxF**
    reference_section_type: OTHER
  - statement: MxaB may form a non-canonical two-component system with the integral
      membrane histidine kinase MxaY, though direct mechanism in AM1 remains unresolved.
    supporting_text: an associated membrane histidine kinase **MxaY** potentially forming
      a non-canonical two-component pair
    reference_section_type: OTHER
  - statement: During the lanthanide switch the mxa operon is downregulated while xox
      operon genes are upregulated.
    supporting_text: during the lanthanide (Ln) switch, the **mxa operon is downregulated**
    reference_section_type: OTHER
  - statement: No evidence indicates that MxaB is an enzyme or transporter; it is consistently
      treated as a transcriptional regulator.
    supporting_text: No evidence retrieved indicates that MxaB is an enzyme or transporter.
    reference_section_type: OTHER
  - statement: The best-supported localization is a cytosolic/nucleoid-associated DNA-binding
      transcription factor that regulates transcription of the mxa operon.
    supporting_text: 'Cytosol/nucleoid-associated:** DNA-binding transcription factor
      that regulates transcription of the mxa operon'
    reference_section_type: OTHER
  - statement: It remains unresolved whether MxaB directly regulates the mxaF/xoxF
      promoters, so detailed mechanistic claims should be made cautiously.
    supporting_text: it remains unresolved whether MxaB directly regulates these promoters
    reference_section_type: OTHER
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms.
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods.
  findings: []
status: COMPLETE

Gene Description

Existing Annotations Review

Core Functions