mxaC encodes a membrane-associated auxiliary protein of 355 amino acids that is essential for methanol oxidation in Methylorubrum extorquens AM1. MxaC contains a von Willebrand factor A (vWFA) domain (residues 86-259) that likely mediates protein-protein interactions and metal coordination, and two transmembrane helices (residues 51-72 and 307-325) that anchor it in the membrane. MxaC is required for incorporation of calcium into the active site of methanol dehydrogenase (MxaFI). Together with MxaS and MxaL (which also contain vWFA domains) and MxaR (a MoxR-class AAA+ ATPase), MxaC likely forms a MoxR/VWA complex specialized in metal cofactor insertion. This evolutionarily conserved prokaryotic assembly machinery facilitates Ca²⁺ transport and incorporation into the PQQ-dependent methanol dehydrogenase complex. MxaC is part of the COG2304 family and is conserved across methylotrophic bacteria that utilize the calcium-dependent methanol oxidation pathway.
Definition: The aggregation, arrangement and bonding together of methanol dehydrogenase complex components
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0046872 metal ion binding | ISS PMID:7592474 Identification and nucleotide sequences of mxaA, mxaC, mxaK,... | NEW | Summary: MxaC contains a von Willebrand factor A (VWA) domain that typically mediates metal coordination, and the gene is required for incorporation of Ca2+ into the catalytic center of methanol dehydrogenase (MxaF). The 2025 assembly study frames the metal-loading role as inferential rather than a directly demonstrated biochemical activity of MxaC, so this ISS annotation is retained as a domain-based inference only. Reason: MxaC is required for Ca2+ incorporation into the MxaF active site and contains a VWA domain (residues 86-259) of a family that can coordinate divalent cations via a MIDAS motif. Direct metal binding by MxaC itself has not been demonstrated, so this remains an inferred (ISS) annotation. Supporting Evidence: file:METEA/mxaC/mxaC-deep-research-falcon.md with the assistance of proteins … MxaC … Ca2+ is incorporated into the catalytic center of MxaF file:METEA/mxaC/mxaC-deep-research-falcon.md von Willebrand factor A (VWA) domain-containing auxiliary protein |
| GO:0016020 membrane | IEA file:METEA/mxaC/mxaC-uniprot.txt | NEW | Summary: MxaC is predicted to contain two transmembrane helices (residues 51-72 and 307-325; Phobius) that anchor it in the membrane. The falcon report places the auxiliary MxaC at the periplasm-facing MDH biogenesis pathway but notes no direct localization assay exists for MxaC itself. Reason: UniProt (Phobius) predicts two transmembrane helices, supporting membrane association. This is a low-resolution computational (IEA) localization; the precise topology and periplasmic association are inferred from MDH pathway context, not directly demonstrated. Supporting Evidence: file:METEA/mxaC/mxaC-uniprot.txt TRANSMEM 51..72 file:METEA/mxaC/mxaC-uniprot.txt TRANSMEM 307..325 |
| GO:0065003 protein-containing complex assembly | IMP PMID:7592474 Identification and nucleotide sequences of mxaA, mxaC, mxaK,... | NEW | Summary: MxaC is required for production of active methanol dehydrogenase. Classic mutant complementation (Morris et al., 1995) showed mxaC is required for methanol oxidation, and a 2025 mechanistic study showed that deleting mxaC yields inactive MDH, placing MxaC among the auxiliary proteins required for MDH maturation/assembly. Reason: Mutant complementation showed mxaC is required for methanol oxidation, and deletion of mxaC produces inactive MDH, indicating a role in assembly/maturation of the methanol dehydrogenase complex. Supporting Evidence: PMID:7592474 mutant complementation studies showed that mxaC is required for methanol oxidation file:METEA/mxaC/mxaC-deep-research-falcon.md auxiliary proteins required for MDH maturation |
| GO:0051131 chaperone-mediated protein complex assembly | NAS | NEW | Summary: MxaC is a VWA-domain auxiliary factor proposed to act with the MoxR-class AAA+ ATPase MxaR (and VWA proteins MxaS, MxaL) in a MoxR/VWA module during MDH biogenesis. MoxR/VWA systems function as chaperone-like assembly factors, supporting this term as the most specific available description of MxaC's assembly role. MxaC is not part of the mature MxaFI enzyme. Reason: Falcon deep research groups MxaC with MxaR/MxaS/MxaL in a putative MoxR/VWA assembly module acting as a chaperone-like maturation machinery for methanol dehydrogenase; MxaC does not form part of the finished enzyme. Supporting Evidence: file:METEA/mxaC/mxaC-deep-research-falcon.md MoxR/VWA complex file:METEA/mxaC/mxaC-deep-research-falcon.md grouped with other VWA proteins (e.g., MxaS, MxaL) and a **MoxR-class AAA+ ATPase (MxaR)** |
| GO:0006816 calcium ion transport | NAS | NEW | Summary: MxaC participates in incorporation of Ca2+ into the catalytic center of MxaF during MDH maturation. Whether MxaC mediates membrane transport of Ca2+ or only its delivery/loading at the active site is not established; the falcon report frames the metal-handling role as inferential and does not demonstrate transmembrane Ca2+ transport. Reason: The supported role is Ca2+ incorporation/loading during MDH assembly. This broad transport term is added tentatively (NAS) to capture the calcium-handling aspect; demonstrated transmembrane calcium transport by MxaC has not been shown. Supporting Evidence: file:METEA/mxaC/mxaC-deep-research-falcon.md with the assistance of proteins … MxaC … Ca2+ is incorporated into the catalytic center of MxaF |
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