ECF238

ECF subgroups

ECF238s1 25 ECF238s2 75 ECF238s3 44 ECF238s4 31 ECF238s5 24 ECF238s6 32 ECF238s7 8 ECF238s8 13 ECF238s9 18 ECF238s10 32 ECF238s11 23 ECF238s12 13 ECF238s13 23 ECF238s14 20 ECF238s15 17 ECF238s16 7 ECF238s17 19 ECF238s18 16 ECF238s19 15 ECF238s20 16 ECF238s21 17 ECF238s22 10 ECF238s23 14 ECF238s24 12 ECF238s25 13 ECF238s26 11 ECF238s27 0 ECF238s28 11 ECF238s29 9

ECF proteins

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).

Genomic context conservation: Conserved proteins in the context of ECF238 are limited to subgroup ECF238s2, with a permease and a thioredoxin-domain-containing protein. 

Anti-σ factor: Members of ECF238 are not associated with AS factors.

Promoter motif conservation: Predicted target promoter motifs are not conserved, indicating that ECF238 is not autoregulated. This seems to be the case of SigZ (Luo et al., 2010).

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 SigZ’s 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).