ECF40 ECF proteins

General description: Members of this group belong to Actinobacteria (100%) and have homology to proteins from the original group ECF40 (98.37%). Proteins from ECF40 contain a pair of cysteine residues in the σ2 domain that could take part in their regulation.

Anti-σ factor: Position +1 contains a putative RsdA-like AS factor in subgroups ECF40s1 (0.81 per ECF), ECF40s3 (0.3 per ECF), ECF40s6 (0.5 per ECF) and ECF40s8 (0.25 per ECF). Nevertheless, when looking at the MSA, only putative AS factors from ECF40s1 and ECF40s2 are homologous and contain one clear transmembrane helix (50% in consensus with TopCons, ~100% in the MSA). Interestingly, 17.31% of the putative AS factors from ECF40s1 are fused to a YfdX-like domain. YdfX bind antibiotics in a multi-drug resistant strain of Salmonella thyphi (Saha, Manna, Das, & Ghosh, 2016).

Genomic context conservation: The genetic context of proteins from ECF40 contains one or two proteins with an IMP dehydrogenase/GMP reductase domain (except ECF40s4 and ECF40s5) involved in purine metabolism, ~3 protein kinases per ECF in ECF40s2, a DUF5319-containing protein (+2 of ECF40s1 and ECF40s3), a transcription factor WhiB (-1 of ECF40s3 and -2 of ECF40s2), a LytR cell envelope-related transcriptional attenuator (-8 of ECF40s4), a DUF4193-containing protein (-7 of ECF40s4), a DUF3093-containing protein (-6 of ECF40s4), a dUTPase (-5 of ECF40s4), a DUF3710-containing protein (-4 of ECF40s4), an OB-fold nucleic acid binding domain (-2 of ECF40s4), a DUF3159-containing protein (-1 of ECF40s4), TrkA (+1 and +2 of ECF40s4), an amino acid permease (+3 of ECF40s4), a protein from the TCP-1/cpn60 chaperonin family (ECF40s2, ECF40s6 and -1 of ECF40s9), the 10 Kd subunit of a chaperonin (ECF40s6 and -2 of ECF40s9), a response regulator fused to a LuxR transcriptional regulator (-1 of ECF40s2),  a LysR substrate binding domain fused to a bacterial regulatory helix-turn-helix protein of the LysR family (-3 of ECF40s2), a GMP synthase (ECF40s3),  a glycoprotease (ECF40s9, ECF40s3 and ECF40s1), an inositol monophosphatase (ECF40s4), DUF541 (ECF40s4), an alpha-glycerophosphate oxidase (ECF40s2 and ECF40s9) and a short chain dehydrogenase (ECF40s2).

Studied members: Two characterized members of this group, SigD from Corynebacterium glutamicum and Corynebacterium tuberculosis (ECF40s3) are associated with AS factors encoded in position +1. SigD from Corynebacterium glutamicum is involved in mycolate synthesis and lysozyme resistance (Toyoda & Inui, 2017). Another member of ECF40, SigD from Mycobacterium tuberculosis (ECF40s1), is associated with nutrient starvation, protein folding and fatty acid degradation, and has been associated the AS factor RsdA, subjected to RIP by Rip1 protease and encoded in +1 (Jaiswal, Prabha, Manjeera, & Gopal, 2013; Schneider, Sklar, & Glickman, 2014).

Promoter motif conservation: The promoter motifs of members of ECF40 are not conserved, even though SigD from M. tuberculosis is auto-inducible (Calamita et al., 2004; Raman, Hazra, Dascher, & Husson, 2004). Analysis of the sigmulon of SigD in C. glutamicum revealed conserved promoter binding motifs with GTAACA/G in -35 and GAT in -10 (Pátek et al., 2018), slightly different from SigD in M. tuberculosis. Moreover, promoters of SigD in C. glutamicum are also recognized by SigH (ECF12s2) and contain overlapping or closely located housekeeping or SigB-regulated promoters (Pátek et al., 2018).

Summary: ECF40 is regulated by RsdA-like AS factors usually located in position +1, but absent from the genetic context in other cases. Aside from the AS factor, members of ECF40 could be regulated by the binding or release of a putative disulfide bridge between the conserved pair of cysteine residues located in the σ2 domain. This pair of residues coexists with the AS factor, indicating a possible two-layered regulation of ECF40.


Basic information

Number of representative ECFs: 1975

Number of non-redundant ECFs: 1652

Sequences with C-terminal extension: 0.42%

Sequences with N-terminal extension: 10.47%

Overrepresented phylum: Actinobacteria [99.95%]

Sample Neighborhood

Protein WP_010839377.1 of Assembly GCF_000389715.1 (Rhodococcus rhodnii LMG 5362)

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
Transcription regulation by the Mycobacterium tuberculosis alternative sigma factor SigD and its role in virulence. Journal of bacteriology 2004 S. Raman, R. Hazra, C. Dascher, R. Husson PubMed: 15375142 ECF40
The Mycobacterium tuberculosis SigD sigma factor controls the expression of ribosome-associated gene products in stationary phase and is required for full virulence. Cellular microbiology 2005 H. Calamita, C. Ko, S. Tyagi, T. Yoshimatsu, N. Morrison, W. Bishai PubMed: 15659067 ECF40
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
Mycobacterium tuberculosis RsdA provides a conformational rationale for selective regulation of σ-factor activity by proteolysis. Nucleic acids research 2013 R. Jaiswal, T. Prabha, G. Manjeera, B. Gopal PubMed: 23314154 ECF17, ECF40
The Rip1 protease of Mycobacterium tuberculosis controls the SigD regulon. Journal of bacteriology 2014 J. Schneider, J. Sklar, M. Glickman PubMed: 24816608 ECF40
Antibiotic binding of STY3178, a yfdX protein from Salmonella Typhi. Scientific reports 2016 P. Saha, C. Manna, S. Das, M. Ghosh PubMed: 26892637 ECF40
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
Extracytoplasmic function sigma factor σ<sup>D</sup> confers resistance to environmental stress by enhancing mycolate synthesis and modifying peptidoglycan structures in Corynebacterium glutamicum. Molecular microbiology 2018 K. Toyoda, M. Inui PubMed: 29148103 ECF40
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