Anti-σ factor: Proteins from this group are associated with RskA-like AS factors in +1. In subgroups from Firmicutes, AS factors are fused to a putative zinc-finger; instead, this domain is not conserved in Bacteroidetes. RskA is the AS factor of SigK from Mycobacterium tuberculosis (ECF19s2). RskA is degraded by regulated intramembrane proteolysis (RIP), has one transmembrane helix and contains a non-zinc-binding class I ASD, composed of four alpha helices (Schumacher et al., 2018). Most of the proteins in position +1 of ECF214 contain only one transmembrane helix (94.33%), supporting the idea that proteins in position +1 are RskA-like AS factors that could be regulated RIP, as in the case of RskA.
Genomic context conservation: The presence of a conserved aspartyl-protease in position -3 of ECF214s10, ECF214s18 and ECF214s6 suggests that this enzyme could be in charge of the first step of the degradation by RIP of the AS factors 79.31% of the proteins in position -3 in these subgroups contain a signal peptide according to TopCons (Tsirigos, Peters, Shu, Käll, & Elofsson, 2015), a prerequisite for a site-1 protease. The aspartyl protease also contains a PDZ domain (PFAM: PDZ or PDZ_2) in ECF214s18. The PDZ domain of the site-1 protease DegS binds unfolded periplasmic proteins, changing the conformation of DegS and allowing for the proteolysis of the anti-σ factor RseA, thereby activating the RpoE-dependent transcription (Hasselblatt et al., 2007; Sohn, Grant, & Sauer, 2007). This suggests a potential activation of members of ECF214s18 by periplasmic unfolded proteins.
Other proteins conserved in the genetic context of the members of ECF214 are UDP-N-acetylenolpyruvoylglucosamine reductase (-1 of ECF214s10, ECF214s18 and ECF214s6), an aminotransferase class I and II (-2 of ECF214s10, ECF214s18 and ECF214s6), an aspartyl protease (-3 of ECF214s10 and ECF214s6) fused to a PDZ domain in ECF214s18, a DUF1573-containing protein (-4 of ECF214s10, ECF214s18 and ECF214s6), a tRNA synthetase (-5 of ECF214s10, ECF214s18 and ECF214s6), a extracellular solute-biding protein (ECF214s4), a secreted repeat of unknown function (-1 of ECF214s4), an ECF from ECF245s2 (+3 of ECF214s10), a radical SAM superfamily protein (+4 of ECF214s10), a glyceraldehyde 3-phosphate dehydrogenase (ECF214s18, ECF214s6 and +5 of ECF214s10), an histidine kinase from a 2CS fused to a receiver domain (+6 of ECF214s10), a tetraacyldisaccharide-1-P 4'-kinase (ECF214s18, ECF214s6 and +7 of ECF214s10), NIF3 (+8 of ECF214s10), a C4-type zinc ribbon domain (+9 of ECF214s10), a penicillin-binding protein (ECF214s18), a MreB/MbI protein (ECF214s18), a DUF4331 (ECF214s1), a pyridine nucleotide-disulphide oxidoreductase (-1 of ECF214s11), an enoyl-(Acyl carrier protein) reductase (ECF214s11), a beta-eliminating lyase (ECF214s11), a DUF2721 (ECF214s11), a fasciclin domain containing protein (ECF214s2).
Promoter motif conservation: The promoter motifs are diverse across subgroups so that a consensus could not be defined. Some groups have TATATACG in -35 and a more variable GGATG in -10 (ECF214s20, ECF214s10, ECF214s18, ECF214s6 and ECF214s2).
Summary: Members of ECF214 are regulated by a RskA-like AS factors that can contain a zinc-finger. In subgroup ECF214s18, ECF214s10 and ECF214s6 these AS factors seem to be degraded by RIP induced by an extracytoplasmic aspartyl protease encoded in position -3, which contains a PDZ domain (in >75% of the proteins only in ECF214s18), in charge of sensing unfolded peptides in the periplasm in DegS from E. coli (Hasselblatt et al., 2007; Sohn et al., 2007).
Number of representative ECFs: 1015
Number of non-redundant ECFs: 1069
Sequences with C-terminal extension: 0.09%
Sequences with N-terminal extension: 0.84%
Overrepresented phylum: Bacteroidetes [70.05%]
|Regulation of the sigmaE stress response by DegS: how the PDZ domain keeps the protease inactive in the resting state and allows integration of different OMP-derived stress signals upon folding stress.||Genes & development||2007||H. Hasselblatt, R. Kurzbauer, C. Wilken, T. Krojer, J. Sawa, J. Kurt, R. Kirk, S. Hasenbein, M. Ehrmann, T. Clausen||PubMed: 17938245||ECF02, ECF214, ECF273|
|Allosteric activation of DegS, a stress sensor PDZ protease.||Cell||2007||J. Sohn, R. Grant, R. Sauer||PubMed: 17981123||ECF214|
|The TOPCONS web server for consensus prediction of membrane protein topology and signal peptides.||Nucleic acids research||2015||K. Tsirigos, C. Peters, N. Shu, L. Käll, A. Elofsson||PubMed: 25969446||ECF214|
|The crystal structure of the RsbN-σBldN complex from Streptomyces venezuelae defines a new structural class of anti-σ factor.||Nucleic acids research||2018||M. Schumacher, M. Bush, M. Bibb, F. Ramos-León, G. Chandra, W. Zeng, M. Buttner||PubMed: 29905823||ECF121, ECF214|