General description: Members of ECF12 are homologous to proteins from original ECF12 (86.15%) and ECF26 (3.5%). Members of ECF12 are mainly present in Actinobacteria (88.76%), but also in Bacteroidetes (6.91%), Proteobacteria (1.75%), Chlorobi (1.24%), Ignavibacteriae (0.31%), Planctomycetes (0.21%), Firmicutes (0.10%) and Calditrichaeota (0.10%).
Regulation: As in the original group ECF12 (Staroń et al., 2009), the genetic neighborhood of most of the members of new ECF12 contain a putative AS factor in position +1. These putative AS factors contain a zinc-finger and are soluble (96.05%), except in the case of subgroup ECF12s19, where the putative AS factors are transmembrane.
Special features: No putative AS factor is present for some of the smaller subgroups, which could be encoded somewhere else in the genome. One of these subgroups is ECF12s9. It contains an ECF from ECF12s2 in +1 in three out of four proteins from representative genomes. Interestingly, none of the ECFs from ECF12s9 has a putative AS associated, they are transcribed convergently, and their 3 ends are overlapping, which could indicate that these ECFs are mutually exclusive and only one can be expressed at a time. Regulation by transcriptional interference caused by convergent, overlapping transcripts has been shown to resolve in RNAP collision, truncated RNA (Shearwin, Callen, & Egan, 2005) and was used to generate bistable switch that responds to a signaling molecule in Streptomyces coelicolor (Chatterjee et al., 2011). If this is a regulatory mechanism for members of ECF12s9 and some members of ECF12s2, it remains unclear what triggers the switch towards the opposite ECF and what are the differences in the response mediated by these two ECFs, given their high sequence similarity. Subgroup ECF12s22, with a single sequence from representative/reference genomes, contains a σ factor in position +1 and lacks an evident putative AS factor. Nevertheless, the two σ factors are encoded in tandem, non-overlapping configuration, discarding a transcriptional interference mechanism in this subgroup.
Studied members: One of the members of ECF12, σR from Streptomyces coelicolor (ECF12s1), responds to thiol-oxidative stress by inducing thioredoxin, mycothiol metabolism, proteases, among others (Kim, Hahn, Cho, Cho, & Roe, 2009). σR is activated when its AS factor, RsrA, forms disulfide bonds within its zinc-binding domain under exposure to oxidation agents and disulfide stress (Paget et al., 2001; Zdanowski et al., 2006). Upon stress exposure, σR induces its expression from an earlier promoter that produces a variant of σR (σR) 55aa longer and more prone to be degraded by the also upregulated ClpP1/P2 proteases (Kim et al., 2009). It is not clear whether this promoter-shift mechanism is present in other members of ECF12.
SigH from M. tuberculosis (ECF12s1) is induced by heat, oxidative and nitric oxide stresses and it activates the expression of a broad set of genes involved in DNA repair, sulfur metabolism and translation recovery (Sharp et al., 2016). The AS factor of SigH, RshA, is located in position +2, coordinates a [2Fe-2S] cluster and binds SigH using salt bridges (Kumar et al., 2012). Apart from oxidants, RshA is also inhibited by the eukaryotic-like Ser/Thr kinase PnkB (Park, Kang, & Husson, 2008), which illustrates the integration of different sensing pathways in bacteria. Members of ECF12s1 do not usually contain AS factors in position +2.
Promoter motif conservation: SigH from C. glutamicum (ECF12s2) binds to the same motif a the prediction for its subgroup GGAAT in -35 and GTT in -10 (Pátek et al., 2018). The target promoter of SigH (GGAAYR-(N17-18)-GTT) (Sharp et al., 2016) does not match the motif observed for subgroup ECF12s1, but ECF12s2. In general, predicted promoter motifs for the subgroups of ECF12 are not conserved.
Summary: Members of ECF12 are related to oxidative and disulfide stress response. The soluble AS factors associated to this group coordinate metals that serve to sense oxidative stress and release the inhibition over the ECF. The nature of the metal might differ, even within the same subgroup. Moreover, the putative AS factor is lacking in some subgroups, raising the possibility of another regulatory mechanism such as transcriptional interference in subgroup ECF12s9. Nevertheless, it is possible that their AS factor is encoded somewhere else in the genome.
Number of representative ECFs: 3293
Number of non-redundant ECFs: 3228
Sequences with C-terminal extension: 1.27%
Sequences with N-terminal extension: 27.91%
Overrepresented phylum: Actinobacteria [89.68%]
|Regulation of motility behavior in Myxococcus xanthus may require an extracytoplasmic-function sigma factor.||Journal of bacteriology||1998||M. Ward, H. Lew, A. Treuner-Lange, D. Zusman||PubMed: 9791117||ECF12|
|Mutational analysis of RsrA, a zinc-binding anti-sigma factor with a thiol-disulphide redox switch.||Molecular microbiology||2001||M. Paget, J. Bae, M. Hahn, W. Li, C. Kleanthous, J. Roe, M. Buttner||PubMed: 11251822||ECF12|
|Transcriptional interference--a crash course.||Trends in genetics : TIG||2005||K. Shearwin, B. Callen, J. Egan||PubMed: 15922833||ECF12|
|Assignment of the zinc ligands in RsrA, a redox-sensing ZAS protein from Streptomyces coelicolor.||Biochemistry||2006||K. Zdanowski, P. Doughty, P. Jakimowicz, L. O'Hara, M. Buttner, M. Paget, C. Kleanthous||PubMed: 16819828||ECF12, ECF11|
|Regulation of the SigH stress response regulon by an essential protein kinase in Mycobacterium tuberculosis.||Proceedings of the National Academy of Sciences of the United States of America||2008||S. Park, C. Kang, R. Husson||PubMed: 18728196||ECF12|
|Positive and negative feedback regulatory loops of thiol-oxidative stress response mediated by an unstable isoform of sigmaR in actinomycetes.||Molecular microbiology||2009||M. Kim, M. Hahn, Y. Cho, S. Cho, J. Roe||PubMed: 19682253||ECF12|
|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|
|Convergent transcription in the butyrolactone regulon in Streptomyces coelicolor confers a bistable genetic switch for antibiotic biosynthesis.||PloS one||2011||A. Chatterjee, L. Drews, S. Mehra, E. Takano, Y. Kaznessis, W. Hu||PubMed: 21765930||ECF12|
|Interaction of Mycobacterium tuberculosis RshA and SigH is mediated by salt bridges.||PloS one||2012||S. Kumar, S. Badireddy, K. Pal, S. Sharma, C. Arora, S. Garg, M. Alam, P. Agrawal, G. Anand, K. Swaminathan||PubMed: 22937074||ECF12|
|Comprehensive Definition of the SigH Regulon of Mycobacterium tuberculosis Reveals Transcriptional Control of Diverse Stress Responses.||PloS one||2016||J. Sharp, A. Singh, S. Park, A. Lyubetskaya, M. Peterson, A. Gomes, L. Potluri, S. Raman, J. Galagan, R. Husson||PubMed: 27003599||ECF12|
|The anti-sigma factor RsrA responds to oxidative stress by reburying its hydrophobic core.||Nature communications||2016||K. Rajasekar, K. Zdanowski, J. Yan, J. Hopper, M. Francis, C. Seepersad, C. Sharp, L. Pecqueur, J. Werner, C. Robinson, S. Mohammed, J. Potts, C. Kleanthous||PubMed: 27432510||ECF12|
|Overlap of Promoter Recognition Specificity of Stress Response Sigma Factors SigD and SigH in <i>Corynebacterium glutamicum</i> ATCC 13032.||Frontiers in microbiology||2018||H. Dostálová, T. Busche, J. Holátko, L. Rucká, V. Štěpánek, I. Barvík, J. Nešvera, J. Kalinowski, M. Pátek||PubMed: 30687273||ECF12, ECF40|