MetaCyc Protein: YefM-antitoxin DNA-binding transcriptional repressor
Inferred from experiment

Gene: yefM Accession Numbers: EG12844 (MetaCyc), b2017, ECK2012

Species: Escherichia coli K-12 substr. MG1655

Component of: YefM-YoeB antitoxin/toxin complex and DNA-binding transcriptional repressor (extended summary available)

Subunit composition of YefM-antitoxin DNA-binding transcriptional repressor = [YefM]2
         YefM antitoxin of the YoeB-YefM toxin-antitoxin pair and DNA binding transcriptional repressor = YefM

YoeB and YefM are a toxin-antitoxin pair [Grady03].

YefM has similarity to the Axe protein of the Txe-Axe toxin-antitoxin pair, which is encoded by a multidrug resistance episome isolated from Enterococcus faecium [Grady03].

The YefM protein appears to lack secondary structure, and its native conformation is proposed to be unfolded. A linear recognition element which can be recognized by YoeB was identified using peptide array technology [Cherny04].

Regulation has been described [Ren04]. Transcription is induced upon biofilm formation [Ren04].

Review: [Yamaguchi11]

Map Position: [2,087,486 <- 2,087,737]

Molecular Weight of Polypeptide: 9.308 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0006705, EchoBASE:EB2693, EcoGene:EG12844, EcoliWiki:b2017, OU-Microarray:b2017, PortEco:yefM, Pride:P69346, Protein Model Portal:P69346, RefSeq:NP_416521, RegulonDB:EG12844, SMR:P69346, String:511145.b2017, UniProt:P69346

Relationship Links: InterPro:IN-FAMILY:IPR006442, PDB:Structure:2A6Q, Pfam:IN-FAMILY:PF02604

Gene-Reaction Schematic

Gene-Reaction Schematic

GO Terms:
Biological Process:
Inferred from experimentGO:0044010 - single-species biofilm formation [Kim09]
Inferred from experimentGO:0045892 - negative regulation of transcription, DNA-templated [Kedzierska07]
Inferred by computational analysisGO:0006351 - transcription, DNA-templated [UniProtGOA11a]
Inferred by computational analysisGO:0006355 - regulation of transcription, DNA-templated [UniProtGOA11a]
Molecular Function:
Inferred from experimentGO:0015643 - toxic substance binding [Cherny05]
Inferred from experimentGO:0042803 - protein homodimerization activity [Kedzierska07]
Inferred from experimentGO:0043565 - sequence-specific DNA binding [Kedzierska07]
Inferred by computational analysisGO:0003677 - DNA binding [UniProtGOA11a]

MultiFun Terms: cell processesdefense/survival

DNA binding site length: 14 base-pairs

Symmetry: Inverted Repeat

Consensus DNA Binding Sequence: TCATTGTACAATGA

Created 21-Apr-2011 by Peralta M, UNAM

Subunit of: YefM-YoeB antitoxin/toxin complex and DNA-binding transcriptional repressor

Inferred from experiment

Synonyms: YefMB

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of YefM-YoeB antitoxin/toxin complex and DNA-binding transcriptional repressor = [YoeB][YefM]2
         toxin of the YoeB-YefM toxin-antitoxin pair = YoeB (extended summary available)
         YefM antitoxin of the YoeB-YefM toxin-antitoxin pair and DNA binding transcriptional repressor = YefM

YefM is a transcriptional DNA-binding autorepressor for the yefM-yoeB operon. In addition, YefM also functions as an antitoxin to form a complex with YoeB, which is a toxin that is counteracted by YefM antitoxin [Kedzierska07]. YefM can bind alone with low affinity to the yefM-yoeB operator, but together with YoeB it has an enhanced DNA-binding affinity compared to free YefM [Kedzierska07]. YoeB enhances the interaction with YefM by affecting the YefM conformation to one that is more favorable for DNA binding and/or by stabilizing the nucleoprotein complex at the operator site and reducing basal expression of the yefM-yoeB operon [Kedzierska07, Bailey09].

The yefM gene is upregulated during growth in biofilms [Ren04] and yefM-yoeB is upregulated in persister cells [Shah06]; it is probable that derepression of yefM-yoeB autoregulation occurs in these circumstances in response to an as-yet-unknown environmental or cell cycle signal(s) that interferes with the YefM-YoeB-operator interaction [Bailey09].

The operator site 5' of yefM-yoeB comprises adjacent long (L) and short (S) palindromes with core 5'-TGTACA-3' motifs with a center-to-center distance of 12 bp [Kedzierska07], which was suggested to be crucial for the correct stable positioning of YefM-YoeB at the two repeats [Bailey09]. This sequence organization is common in yefM-yoeB regulatory regions in diverse genomes, suggesting that interaction of YefM-YoeB with these motifs is a conserved mechanism of operon autoregulation [Kedzierska07].

Nevertheless, YefM originally was described as a native unstructured protein [Cherny04]; later it was reevaluated as experimental, and modeling data have demonstrated that the protein is at least partially folded [Kedzierska07, Pomerantsev01] and dimeric [Kedzierska07].

The YefM antitoxin forms a heterotrimeric complex with the YoeB toxin (YefM2-YoeB) [Cherny05, Kamada05]. The tertiary structure of the YoeB toxin and the YefM2-YoeB complex has been described [Kamada05]. In the complex, one C terminus in the YefM homodimer is unfolded and the other one shows an α-helical conformation and conceals the endoribonuclease fold of YoeB. Two N-terminal segments of YefM form a symmetrical dimer within the YefM2-YoeB heterotrimeric complex and do not contact YoeB directly [Bailey09].

YefM does not possess a canonical DNA-binding motif, but instead a pair of basic residues, R10 and R31, conserved in many YefM homologs are absolutely necessary for DNA binding by the YefM-YoeB complex [Grady03, Bailey09, Kamada05].

Molecular Weight: 30.0 kD (experimental) [Kamada05]

Created in EcoCyc 10-Jan-2009 by Santos-Zavaleta A, UNAM
Imported from EcoCyc 30-Sep-2015 by Paley S, SRI International

DNA binding site length: 14 base-pairs

Symmetry: Inverted Repeat

Consensus DNA Binding Sequence: TCATTGTACAATGA

Sequence Features

Feature Class Location Citations Comment
Mutagenesis-Variant 10
Inferred from experiment[Bailey09]
UniProt: Loss of DNA-binding and transcriptional repression.
Mutagenesis-Variant 31
Inferred from experiment[Bailey09]
UniProt: Loss of DNA-binding and transcriptional repression.

Peter D. Karp on Wed Jan 18, 2006:
Gene right-end position adjusted based on analysis performed in the 2005 E. coli annotation update [Riley06].
Peter D. Karp on Thu Jan 16, 2003:
Predicted gene function revised as a result of E. coli genome reannotation by Serres et al. [Serres01].
10/20/97 Gene b2017 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG12844; confirmed by SwissProt match.


Bailey09: Bailey SE, Hayes F (2009). "Influence of operator site geometry on transcriptional control by the YefM-YoeB toxin-antitoxin complex." J Bacteriol 191(3);762-72. PMID: 19028895

Cherny04: Cherny I, Gazit E (2004). "The YefM antitoxin defines a family of natively unfolded proteins: implications as a novel antibacterial target." J Biol Chem 279(9);8252-61. PMID: 14672926

Cherny05: Cherny I, Rockah L, Gazit E (2005). "The YoeB toxin is a folded protein that forms a physical complex with the unfolded YefM antitoxin. Implications for a structural-based differential stability of toxin-antitoxin systems." J Biol Chem 280(34);30063-72. PMID: 15980067

Grady03: Grady R, Hayes F (2003). "Axe-Txe, a broad-spectrum proteic toxin-antitoxin system specified by a multidrug-resistant, clinical isolate of Enterococcus faecium." Mol Microbiol 47(5);1419-32. PMID: 12603745

Kamada05: Kamada K, Hanaoka F (2005). "Conformational change in the catalytic site of the ribonuclease YoeB toxin by YefM antitoxin." Mol Cell 19(4);497-509. PMID: 16109374

Kedzierska07: Kedzierska B, Lian LY, Hayes F (2007). "Toxin-antitoxin regulation: bimodal interaction of YefM-YoeB with paired DNA palindromes exerts transcriptional autorepression." Nucleic Acids Res 35(1);325-39. PMID: 17170003

Kim09: Kim Y, Wang X, Ma Q, Zhang XS, Wood TK (2009). "Toxin-antitoxin systems in Escherichia coli influence biofilm formation through YjgK (TabA) and fimbriae." J Bacteriol 191(4);1258-67. PMID: 19060153

Pomerantsev01: Pomerantsev AP, Golovliov IR, Ohara Y, Mokrievich AN, Obuchi M, Norqvist A, Kuoppa K, Pavlov VM (2001). "Genetic organization of the Francisella plasmid pFNL10." Plasmid 46(3);210-22. PMID: 11735370

Ren04: Ren D, Bedzyk LA, Thomas SM, Ye RW, Wood TK (2004). "Gene expression in Escherichia coli biofilms." Appl Microbiol Biotechnol 64(4);515-24. PMID: 14727089

Riley06: Riley M, Abe T, Arnaud MB, Berlyn MK, Blattner FR, Chaudhuri RR, Glasner JD, Horiuchi T, Keseler IM, Kosuge T, Mori H, Perna NT, Plunkett G, Rudd KE, Serres MH, Thomas GH, Thomson NR, Wishart D, Wanner BL (2006). "Escherichia coli K-12: a cooperatively developed annotation snapshot--2005." Nucleic Acids Res 34(1);1-9. PMID: 16397293

Serres01: Serres MH, Gopal S, Nahum LA, Liang P, Gaasterland T, Riley M (2001). "A functional update of the Escherichia coli K-12 genome." Genome Biol 2(9);RESEARCH0035. PMID: 11574054

Shah06: Shah D, Zhang Z, Khodursky A, Kaldalu N, Kurg K, Lewis K (2006). "Persisters: a distinct physiological state of E. coli." BMC Microbiol 6;53. PMID: 16768798

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Yamaguchi11: Yamaguchi Y, Park JH, Inouye M (2011). "Toxin-antitoxin systems in bacteria and archaea." Annu Rev Genet 45;61-79. PMID: 22060041

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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