{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q836B3","uniProtkbId":"IREB_ENTFA","entryAudit":{"firstPublicDate":"2004-02-16","lastAnnotationUpdateDate":"2026-06-10","lastSequenceUpdateDate":"2003-06-01","entryVersion":93,"sequenceVersion":1},"annotationScore":4.0,"organism":{"scientificName":"Enterococcus faecalis (strain ATCC 700802 / V583)","taxonId":226185,"evidences":[{"evidenceCode":"ECO:0000312","source":"Proteomes","id":"UP000001415"}],"lineage":["Bacteria","Bacillati","Bacillota","Bacilli","Lactobacillales","Enterococcaceae","Enterococcus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"40272164"}],"value":"Peptidoglycan synthesis regulatory protein IreB"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"24080657"}],"value":"Intrinsic resistance of enterococci B"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"24080657"}],"value":"ireB"},"orderedLocusNames":[{"value":"EF_1202"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24080657"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28551334"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34672600"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37688380"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40272164"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"37688380"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"40272164"}],"value":"Involved in the PASTA kinase-mediated signaling pathway regulating peptidoglycan synthesis to maintain cell wall integrity (PubMed:28551334, PubMed:34672600, PubMed:37688380, PubMed:40272164). Negatively modulates IreK PASTA kinase-mediated signaling, acting downstream of IreK (PubMed:24080657, PubMed:28551334). Modulates peptidoglycan (PG) synthesis pathway committed-step enzymes MurAA and MurAB, but via distinct mechanisms (PubMed:40272164). Positively modulates ClpCP-dependent proteolysis of MurAA, thereby regulating peptidoglycan synthesis and inhibiting intrinsic cephalosporin resistance (PubMed:24080657, PubMed:28551334, PubMed:37688380, PubMed:40272164). Negatively modulates enzymatic activity of MurAB, when IreB is unphosphorylated, thereby regulating peptidoglycan synthesis (PubMed:40272164). When IreK kinase activity is low, under low-stress conditions, such as during stationary phase, predominantly unphosphorylated IreB may form a complex with MurAA and MurAB, promoting proteolysis of MurAA and repressing PG synthesis (Probable). In response to cell-wall stressors, IreB phosphorylation increases, positively regulating PG synthesis (Probable)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28551334"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37688380"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"37688380"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"40272164"}],"value":"Homodimer (PubMed:28551334). Dimerization may be required, but not sufficient, for a role in intrinsic cephalosporin resistance (PubMed:28551334). Interacts directly with MurAA in a UDP-GlcNAc and phosphoenolpyruvate substrate-dependent manner; interaction is reduced by phosphorylation of IreB (PubMed:37688380). Interacts directly with murAB, independent of the presence of substrate; interaction is reduced by phosphorylation of IreB (PubMed:37688380). Dimeric, predominantly unphosphorylated, IreB may form a complex with MurAA and MurAB, thereby promoting proteolysis of MurAA when IreK kinase activity is low (Probable)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24080657"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28551334"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34672600"}],"value":"Phosphorylated by Ser/Thr protein kinase IreK (PubMed:24080657, PubMed:34672600). High levels of phosphorylation may inhibit oligomerization (PubMed:28551334). Dephosphorylated by protein phosphatase IreP (PubMed:24080657). Level of phosphorylation increases after treatment with cell-wall disrupting chemicals, including antimicrobial detergent, chlorhexidine and cephalosporin antibiotic, ceftriaxone (PubMed:34672600)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24080657"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28551334"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37688380"}],"value":"Increases resistance to cephalosporin antibiotics about 4-16 fold, in the OG1RF and T1 strains (PubMed:24080657, PubMed:28551334). Resistance increases slightly further in a murAA 'T-115' mutant background in the OG1 strain (PubMed:37688380). Resistance is reduced in an ireK mutant background, but remains significantly higher than wild-type OG1RF strain (PubMed:24080657). Increases resistance to both sodium cholate and nisin in an ireK mutant background in OG1RF (PubMed:24080657). Identical growth kinetics to wild type OG1RF strain, both alone and in combination with ireK mutation (PubMed:24080657). Growth slightly inhibited during hydrogen peroxide stress (PubMed:37688380)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01507"},{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the IreB/ReoM family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":89,"modifier":"EXACT"}},"description":"Peptidoglycan synthesis regulatory protein IreB","featureId":"PRO_0000216967"},{"type":"Modified residue","location":{"start":{"value":4,"modifier":"EXACT"},"end":{"value":4,"modifier":"EXACT"}},"description":"Phosphothreonine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24080657"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34672600"}]},{"type":"Modified residue","location":{"start":{"value":7,"modifier":"EXACT"},"end":{"value":7,"modifier":"EXACT"}},"description":"Phosphothreonine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24080657"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34672600"}]},{"type":"Mutagenesis","location":{"start":{"value":4,"modifier":"EXACT"},"end":{"value":7,"modifier":"EXACT"}},"description":"Phosphorylation is abolished.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24080657"}],"alternativeSequence":{"originalSequence":"TDET","alternativeSequences":["ADEA"]}},{"type":"Mutagenesis","location":{"start":{"value":7,"modifier":"EXACT"},"end":{"value":7,"modifier":"EXACT"}},"description":"Phosphorylation is substantially reduced.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24080657"}],"alternativeSequence":{"originalSequence":"T","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":50,"modifier":"EXACT"},"end":{"value":50,"modifier":"EXACT"}},"description":"In JG4; suppressor mutation which restores resistance to the cephalosporins ceftriaxone and ceftazidime in an ireK mutant background. Abolishes binding to peptidoglycan synthesis protein MurAB and does not impair MurAB catalytic activity. Does not reduce steady-state abundance.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24080657"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40272164"}],"alternativeSequence":{"originalSequence":"D","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":73,"modifier":"EXACT"},"end":{"value":73,"modifier":"EXACT"}},"description":"Similar resistance to cephalosporin antibiotic in an ireB mutant background in the OG1RF strain.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28551334"}],"alternativeSequence":{"originalSequence":"M","alternativeSequences":["W"]}},{"type":"Mutagenesis","location":{"start":{"value":79,"modifier":"EXACT"},"end":{"value":79,"modifier":"EXACT"}},"description":"Increases resistance to cephalosporin antibiotic in an ireB mutant background, almost equivalent to that conferred by expression of wild-type ireB in the OG1RF 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