ECF39 ECF proteins

General description: ECF39 is one of the largest groups, and it is composed of 93 subgroups and 5,506 unique sequences, all from Actinobacteria. The members of this group could be classified against original ECF39 (93.15%) except one clade from the order Micrococcales.

Regulation: Original ECF39 is associated with 2CSs or membrane-bound AS factors (Staroń et al., 2009). We found that the largest subgroups of new ECF39 are associated with two-component systems – in ECF39s1 the response regulator (1.01 proteins with Pfam Response_reg per ECF) is in -1 and the histidine kinase (0.98 proteins with Pfam HATPase_c per ECF) in -2. In ECF39s3, the response regulator (1.12 copies per ECF) is in +2, and the histidine kinase (one copy per ECF) in +3 and in ECF39s2 only the response regulator (1.12 copies per ECF) is conserved. The response regulator contains a fused C-terminal domain of the transcriptional regulatory protein (Pfam: Trans_reg_C) in most cases. The remaining subgroups are likely regulated by putative AS factors encoded in +1 with one transmembrane helix (72.31%). Putative AS factors might contain sensing domains such as PASTA domains, in charge of sensing cell wall antibiotics, or WD40 beta propeller repeats, also present in other ECF groups such as ECF266 or the sensory domain of protein kinases of ECF62 or the C-terminal extension of some members of ECF57.

Genomic context conservation: The subgroups with the most conserved proteins in their genetic context are part of the clade regulated by 2CSs. They contain an AMP-binding enzyme (+1 of ECF39s2), a VanZ-like protein (-4 of ECF39s1) involved in resistance against cell surface-acting antimicrobials such as teicoplanin and encoded within the skin element of SigK in Clostridium difficile (Woods et al., 2018), an endonuclease with a Fe-S cluster involved in base excision DNA repair (-1 of ECF39s3), a DisA bacterial checkpoint controller (ECF39s3), a subtilisin inhibitor-like protein (ECF39s2), a DeoC/LacD family aldolase (ECF39s1), an adenosine/AMP deaminase (ECF39s1), an aldehyde dehydrogenase (ECF39s1) and a protein with a PspC domain (ECF39s1). Other proteins conserved in the genetic context of members of ECF39 include an amidinotransferase (ECF39s9), a ferritin-like protein (ECF39s9), an AAA ATPase domain fused to a MarR transcriptional regulator (ECF39s31), an aminotransferase class I and II (ECF39s35), an EPSP synthase (ECF39s35), an adenylosuccinate lyase (ECF39s14), a beta-eliminating lyase (-1 of ECF39s14) and BetI-type transcriptional repressor fused to a TetR repressor (ECF39s14).

Studied members: Characterized members of ECF39 include SigE (ECF39s3) and SigQ (ECF39s1) from Streptomyces coelicolor, and Sig25 from Streptomyces avermitilis (ECF39s1). They are associated with 2CSs encoded in their genetic context that promotes their expression. SigE (ECF39s3) is involved in resistance to antibiotics that target the peptidoglycan such as lysozyme (Wood & Ohman, 2015). Instead, Sig25 and SigQ (ECF39s1) induce the synthesis of antibiotics – Sig25 induces expression of oligomycin and represses avermectin (Luo et al., 2014), whereas SigQ induces actinorhodin, undecylprodigiosin and calcium-dependent antibiotic (Shu et al., 2009). SigQ is also involved in sporulation (Shu et al., 2009).

Promoter motif conservation: Predicted target promoter motifs usually contain CAACC in -35 and CGTC in -10, in agreement with original ECF39 (Rhodius et al., 2013). This promoter motif agrees with the one of RpoE in S. coelicolor (Tran et al., 2019). Nevertheless, the three groups regulated by 2CSs do not have clear promoter motifs, probably because not the σ factor, but the 2CS, is regulating the expression of these ECFs.

Summary: ECF39 is involved in antibiotic production and cell wall stress response. Proteins from this group are associated with 2CS in ECF39s1, ECF39s3, and ECF39s2, and to AS factors in other subgroups, as in the case of the original group ECF39 (Staroń et al., 2009). Promoter motifs are not conserved in 2CS-regulated subgroups, potentially because the regulation is carried out by the response regulator. In the remaining subgroups, they are similar to the ones of original ECF39 (Rhodius et al., 2013).


Basic information

Number of representative ECFs: 5809

Number of non-redundant ECFs: 5506

Sequences with C-terminal extension: 3.18%

Sequences with N-terminal extension: 9.50%

Overrepresented phylum: Actinobacteria [99.98%]

Sample Neighborhood

Protein WP_018349468.1 of Assembly GCF_000379825.1 (Longispora albida DSM 44784)

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
Evidence that the extracytoplasmic function sigma factor sigmaE is required for normal cell wall structure in Streptomyces coelicolor A3(2). Journal of bacteriology 1998 M. Paget, L. Chamberlin, A. Atrih, S. Foster, M. Buttner PubMed: 9864331 ECF39
afsQ1-Q2-sigQ is a pleiotropic but conditionally required signal transduction system for both secondary metabolism and morphological development in Streptomyces coelicolor. Applied microbiology and biotechnology 2009 D. Shu, L. Chen, W. Wang, Z. Yu, C. Ren, W. Zhang, S. Yang, Y. Lu, W. Jiang PubMed: 18949475 ECF39
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
Design of orthogonal genetic switches based on a crosstalk map of σs, anti-σs, and promoters. Molecular systems biology 2013 V. Rhodius, T. Segall-Shapiro, B. Sharon, A. Ghodasara, E. Orlova, H. Tabakh, D. Burkhardt, K. Clancy, T. Peterson, C. Gross, C. Voigt PubMed: 24169405 ECF22, ECF27, ECF03, ECF21, ECF39, ECF25, ECF26, ECF42, ECF38, ECF14, ECF29, ECF33, ECF281, ECF290, ECF291
An extracytoplasmic function sigma factor, σ(25), differentially regulates avermectin and oligomycin biosynthesis in Streptomyces avermitilis. Applied microbiology and biotechnology 2014 S. Luo, D. Sun, J. Zhu, Z. Chen, Y. Wen, J. Li PubMed: 24811406 ECF39
Cell wall stress activates expression of a novel stress response facilitator (SrfA) under σ22 (AlgT/U) control in Pseudomonas aeruginosa. Microbiology (Reading, England) 2015 L. Wood, D. Ohman PubMed: 25336469 ECF39
The C. difficile clnRAB operon initiates adaptations to the host environment in response to LL-37. PLoS pathogens 2018 E. Woods, A. Edwards, K. Childress, J. Jones, S. McBride PubMed: 30125334 ECF39
Defining the regulon of genes controlled by σ<sup>E</sup> , a key regulator of the cell envelope stress response in Streptomyces coelicolor. Molecular microbiology 2019 N. Tran, X. Huang, H. Hong, M. Bush, G. Chandra, D. Pinto, M. Bibb, M. Hutchings, T. Mascher, M. Buttner PubMed: 30907454 ECF39
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