General description: This is the second largest ECF group, with 12,157 unique proteins. Proteins from ECF41 have homology against original group ECF41 (99.09%) and they appear primary in Actinobacteria (78.48%), but also in Proteobacteria (14.49%), Firmicutes (Bacillales) (4.88%), Acidobacteria (0.67%), Cyanobacteria (0.49%), Chloroflexi (0.35%), Bacteroidetes (0.21%), Verrucomicrobia (0.11%), Planctomycetes (0.07%), Gemmatimonadetes (0.04%) and Armatimonadetes (0.04%). Proteins from ECF41 contain a C-terminal extension of ~120 aa with a SnoaL-like domain with structural homology to epoxide hydrolases (Goutam, Gupta, & Gopal, 2017; Sultana et al., 2004), likewise the neighboring groups ECF56, ECF295, and ECF294. This C-terminal extension has a regulatory role since the removal of the distal part of the C-terminal extension yields a variant with enhanced activity, whereas the removal of the proximal part of the C-terminus extension drives the ECF inactive (Wecke et al., 2012). This C-terminal extension is a structural domain that tethers σ2 and σ4 domains in the right conformation for its activity and might bind small molecules that modulate the ECF σ factor conformation (Goutam, Gupta, & Gopal, 2017). Therefore, the C-terminal extension of members of ECF41 seems to function as a modulator of the ECF activity rather than an inhibitor (Goutam et al., 2017; Wecke et al., 2012).
Genomic context conservation: Proteins from ECF41 do not contain any conserved protein in their genetic context other than a flavin-containing amine oxidoreductase (Pfam: Amino_oxidase) in -1 of subgroups ECF41s14, ECF41s24, ECF41s30 and ECF41s39, and a carboxymuconolactone decarboxylase (Pfam: CMD) ECF41s8 and in -1 of proteins from ECF41s6 and ECF41s16. These two proteins were already identified in members of the original group ECF41 (Staroń et al., 2009). Other proteins conserved in the genomic context are a DoxX-like protein in -1 of ECF41s13, a F420H(2)-dependent quinone reductase in ECF41s12, a DUF1059 in ECF41s20 and several proteins in the genetic neighborhood of ECF41s25 (NIF3, CobD/Cbib protein, a low molecular weight phosphotyrosine protein phosphatase, a bacterial transferase hexapeptide and an alanine dehydrogenase/PNT).
Studied members: Among the members of ECF41 there is SigJ (ECF41s9) and SigI (ECF41s27) from M. tuberculosis. Both proteins are involved in oxidative stress response. SigI is activating the transcription of an ATP synthase, heat shock proteins, and the catalase/peroxidase KatG, and it plays a role with the response to isoniazid since the deletion mutant is resistant to this antibiotic probably due to the decreased transcription of KatG, which activates isoniazid (Lee et al., 2012) (reviewed in (Souza et al., 2014)). SigJ is involved in resistance against hydrogen peroxide in a KatG-independent manner (Hu, Kendall, Stoker, & Coates, 2004).
Promoter motif conservation: Predicted target promoter motifs are conserved and usually contain TGTCACA in -35 and CGTC in -10, in agreement with the original ECF41 (Wecke et al., 2012). Indeed, Ecf41 from Rhodobacter sphaeroides and Bacillus licheniformis control its expression and one of the coding sequence in -1 (Wecke et al., 2012) exclusively.
Summary: ECF41 is involved in oxidative stress response. It has a SnoaL-like domain fused in C-terminal that exerts a regulatory role. It has been suggested that this domain can bind subtracts and change the conformation of the σ2 and σ4 domains, allowing promoter recognition and RNAP binding as a consequence (Goutam et al., 2017). It is possible that this is also part of the regulatory mechanism behind ECF56, ECF294, and ECF295.
Number of representative ECFs: 10511
Number of non-redundant ECFs: 12157
Sequences with C-terminal extension: 99.37%
Sequences with N-terminal extension: 0.42%
Overrepresented phylum: Actinobacteria [77.63%]
|The Mycobacterium tuberculosis sigJ gene controls sensitivity of the bacterium to hydrogen peroxide.||FEMS microbiology letters||2004||Y. Hu, S. Kendall, N. Stoker, A. Coates||PubMed: 15321691||ECF41|
|The third pillar of bacterial signal transduction: classification of the extracytoplasmic function (ECF) sigma factor protein family.||Molecular microbiology||2009||A. Staroń, H. Sofia, S. Dietrich, L. Ulrich, H. Liesegang, T. Mascher||PubMed: 19737356||ECF103, ECF21, ECF123, ECF51, ECF39, ECF281, ECF102, ECF130, ECF122, ECF291, ECF15, ECF242, ECF22, ECF285, ECF106, ECF27, ECF31, ECF240, ECF114, ECF16, ECF38, ECF41, ECF105, ECF116, ECF111, ECF03, ECF239, ECF42, ECF294, ECF17, ECF11, ECF29, ECF235, ECF293, ECF118, ECF265, ECF30, ECF23, ECF14, ECF249, ECF18, ECF115, ECF290, ECF25, ECF121, ECF02, ECF120, ECF289, ECF28, ECF243, ECF19, ECF43, ECF107, ECF12, ECF32, ECF36, ECF292, ECF286, ECF271, ECF26, ECF40, ECF56, ECF33|
|Isoniazid resistance without a loss of fitness in Mycobacterium tuberculosis.||Nature communications||2012||J. Lee, N. Ammerman, S. Nolan, D. Geiman, S. Lun, H. Guo, W. Bishai||PubMed: 22434196||ECF41|
|Extracytoplasmic function σ factors of the widely distributed group ECF41 contain a fused regulatory domain.||MicrobiologyOpen||2012||T. Wecke, P. Halang, A. Staroń, Y. Dufour, T. Donohue, T. Mascher||PubMed: 22950025||ECF41|
|σ(ECF) factors of gram-positive bacteria: a focus on Bacillus subtilis and the CMNR group.||Virulence||2014||B. Souza, T. Castro, R. Carvalho, N. Seyffert, A. Silva, A. Miyoshi, V. Azevedo||PubMed: 24921931||ECF41, ECF14|
|The fused SnoaL_2 domain in the Mycobacterium tuberculosis sigma factor σJ modulates promoter recognition.||Nucleic acids research||2017||K. Goutam, A. Gupta, B. Gopal||PubMed: 28934483||ECF41|