ECF238 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).


Basic information

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%]

Sample Neighborhood

Protein WP_025761898.1 of Assembly GCF_000566685.1 (Dyadobacter tibetensis Y620-1)

Promoter Motif


Protein sequence length distribution

Gene neighbourhood conservation analysis

Overall Pfam domain distribution: Cumulative frequency of Pfam domains across the genetic neighborhoods. Frequency is expressed as number of Pfam domains per ECF sigma factor. Only domains present in more than 75% of the neighborhoods are shown. Genetic neighborhoods contain the proteins encoded in ±10 from the ECF coding sequence. Only the non-overlapping, highest scoring domains are considered positive. If a protein contains several copies of a domain, only one instance is further considered. In order to avoid sequence bias, only proteins from assemblies defined as "representative" or "reference" by NCBI are included (see
Pfam domain distribution per position: Frequency of Pfam domain architectures in the proteins encoded in ±10 (x-axis) from the ECF coding sequences. Frequency is expressed as number of times a certain domain architecture appears per ECF sigma factor. Only the highest scoring domains with no position overlap are considered in the domain architectures. Note that the order of the Pfam domains in domain architectures may differ from their name. When a protein contains several copies of a domain, only one instance is further considered. Only domain architectures present in more than 20% of the proteins encoded in any position are shown. In order to avoid sequence bias, only proteins from assemblies defined as "representative" or "reference" by NCBI are included (see

Related publications

Title Journal Year Authors PubMed ECF groups
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
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