General description: Members of ECF238 have homology against original ECF24 (84.87%) and ECF44 (13.09%), the latter only present in an internal clade of ECF238. The taxonomic composition is diverse, with proteins present mainly in Proteobacteria (56.37%) and Bacteroidetes (27.94%), but also in Firmicutes (6.37%), Actinobacteria (4.90%), Acidobacteria (2.94%), Nitrospirae (0.49%), Spirochaetes (0.49%) and Chloroflexi (0.49%).
Special features: We found that members of ECF238 contain conserved cysteine residues in the linker and a Cys-rich domain (CRD) in C-terminus. The CxC motif of the linker typically appears in the internal clade composed by the members of original ECF44 (ECF238s13, ECF238s18, ECF238s10, ECF238s26, ECF238s15, and ECF238s29).
Studied members: One of the described members of ECF238, CorE2 from Myxococcus xanthus (ECF238s15), is known to be activated by Cd and Zn via its CRD in C-terminus (Marcos-Torres, Pérez, Gómez-Santos, Moraleda-Muñoz, & Muñoz-Dorado, 2016; Torres, Muñoz-Dorado, & Moraleda-Muñoz, 2018). The binding rearranges the conformation of CorE2 and turns it active. CorE2 also contains a CxC motif in the linker between σ2 and σ4 essential for CorE2 functionality (Marcos-Torres et al., 2016; Torres et al., 2018). Another characterized member is SigZ from Bacillus subtilis (ECF238s9). SigZ is not regulated by any AS factor and the studies about its function are very limited since its deletion does not cause a significant phenotype and it is expressed at a low level under a range of growth conditions (Luo, Asai, Sadaie, & Helmann, 2010). SigZ is involved together with sigV, sigY and YlaC in resistance to the antibiotics cephalosporin, ciprofloxacin and ofloxacin (Luo et al., 2010).
Anti-σ factor: Members of ECF238 are not associated with AS factors.
Summary: All in all, ECF238 is a new group of proteins that are putatively regulated by the binding of metals to Cys-rich regions present in C-terminus and in the linker, as experimentally supported in the case of CarE2 (ECF238s15) and CarE (ungrouped in our classification) (Marcos-Torres et al., 2016; Torres et al., 2018). This novel mechanism could be part of B. subtilis SigZs response, suggesting a solution for the long-standing enigma of its activation signal. All in all, the presence of metal-binding Cys-rich regions in members of ECF238 indicates that this group is involved in metal homeostasis. This response differs from the traditional metal uptake FecI-like groups in that members ECF238 ease metal-associated toxicity effects rather than inducing metal uptake. Interestingly, members of ECF238 seems to not self-regulate their expression, a typical feature of FecI-like σ factors. This similarity between FecI-like members and ECF238 is reflected in the phylogenetic tree ECF238 and ECF237 are the closest groups to the clade of FecI-like σ factors. The specific metal that induces the response in ECF238 might be different since the specificity changes from Cu in CorE to Cd in CorE2 due to the lack of only one cysteine in their CRD (Torres, Muñoz-Dorado, & Moraleda-Muñoz, 2018).
Number of representative ECFs: 568
Number of non-redundant ECFs: 833
Sequences with C-terminal extension: 1.44%
Sequences with N-terminal extension: 0.60%
Overrepresented phylum: Proteobacteria [60.92%]
|Transcriptomic and phenotypic characterization of a Bacillus subtilis strain without extracytoplasmic function σ factors.||Journal of bacteriology||2010||Y. Luo, K. Asai, Y. Sadaie, J. Helmann||PubMed: 20817771||ECF238|
|In depth analysis of the mechanism of action of metal-dependent sigma factors: characterization of CorE2 from Myxococcus xanthus.||Nucleic acids research||2016||F. Marcos-Torres, J. Pérez, N. Gómez-Santos, A. Moraleda-Muñoz, J. Muñoz-Dorado||PubMed: 26951374||ECF238, ECF287, ECF288|
|The complex global response to copper in the multicellular bacterium Myxococcus xanthus.||Metallomics : integrated biometal science||2018||J. Pérez, J. Muñoz-Dorado, A. Moraleda-Muñoz||PubMed: 29961779||ECF238, ECF287, ECF288|