{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q3J0R9","uniProtkbId":"ISCR_CERS4","entryAudit":{"firstPublicDate":"2023-11-08","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2005-11-08","entryVersion":94,"sequenceVersion":1},"annotationScore":4.0,"organism":{"scientificName":"Cereibacter sphaeroides (strain ATCC 17023 / DSM 158 / JCM 6121 / CCUG 31486 / LMG 2827 / NBRC 12203 / NCIMB 8253 / ATH 2.4.1.)","commonName":"Rhodobacter sphaeroides","taxonId":272943,"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"ABA79615.1"},{"evidenceCode":"ECO:0000312","source":"Proteomes","id":"UP000002703"}],"lineage":["Bacteria","Pseudomonadati","Pseudomonadota","Alphaproteobacteria","Rhodobacterales","Paracoccaceae","Cereibacter"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"HTH-type transcriptional regulator IscR"}}},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"26235649"}],"value":"iscR"},"orderedLocusNames":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"RHOS4_20470"}],"orfNames":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"ABA79615.1"}],"value":"RSP_0443"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"B5XNJ6"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26235649"}],"value":"Regulates the transcription of several operons and genes involved in the biogenesis of Fe-S clusters and Fe-S-containing proteins (By similarity). Functions as a transcriptional repressor of genes involved in iron metabolism by directly binding to the promoter region of genes preceded by the Iron-Rhodo-box motif (PubMed:26235649). Binds to iscR and hemP promoter regions independently of an Fe-S cluster, but their transcriptional repression is Fe-S cluster-dependent (PubMed:26235649). Seems to activate some target genes in a Fe-S cluster-independent manner (PubMed:26235649). Negatively regulates its own transcription in the presence of iron only (PubMed:26235649)"}],"commentType":"FUNCTION"},{"commentType":"COFACTOR","cofactors":[{"name":"[2Fe-2S] cluster","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26235649"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:190135"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AGK8"}],"value":"Binds 1 [2Fe-2S] cluster."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26235649"}],"value":"Normal growth under iron-replete conditions, but impaired growth under iron limitation (PubMed:26235649). Exhibits significantly increased ROS levels in iron-replete and iron-deplete conditions (PubMed:26235649). Differential gene expression of genes involved in iron homeostasis as well as genes preceded by an Iron-Rhodo-box motif (PubMed:26235649). Higher expression levels for genes with predicted functions in ferric/ferrous iron uptake or iron storage (PubMed:26235649). Lower expression levels for genes encoding proteins involved in adaptation to cold stress, oxidative stress, glycolysis, pyruvate decarboxylation, flagellum biosynthesis and chemotaxis (PubMed:26235649). Abolished expression of gene iscS downstream in the operon (PubMed:26235649). Induction of iscR expression in the presence of iron (PubMed:26235649). Under iron-limiting conditions, shows defect in iscR repression (PubMed:26235649)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"26235649"}],"value":"IscR proteins typically ligate an Fe-S cluster in their C-terminal part by using three Cys residues and one histidine residue. This motif is conserved in many proteobacteria, but only a single Cys residue involved in Fe-S coordination is present in the C-terminal part of Rhodobacteraceae IscR at a position not matching the Fe-S coordinating Cys residues of other IscR proteins"}],"commentType":"MISCELLANEOUS"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":155,"modifier":"EXACT"}},"description":"HTH-type transcriptional regulator IscR","featureId":"PRO_0000458926"},{"type":"Domain","location":{"start":{"value":2,"modifier":"EXACT"},"end":{"value":136,"modifier":"EXACT"}},"description":"HTH rrf2-type","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00540"}]},{"type":"DNA binding","location":{"start":{"value":30,"modifier":"EXACT"},"end":{"value":53,"modifier":"EXACT"}},"description":"H-T-H motif","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00540"}]},{"type":"Region","location":{"start":{"value":141,"modifier":"EXACT"},"end":{"value":145,"modifier":"EXACT"}},"description":"Heme regulatory motif (HRM)","evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"26235649"}]},{"type":"Binding site","location":{"start":{"value":142,"modifier":"EXACT"},"end":{"value":142,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:190135"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26235649"}],"ligand":{"name":"[2Fe-2S] cluster","id":"ChEBI:CHEBI:190135"}},{"type":"Mutagenesis","location":{"start":{"value":93,"modifier":"EXACT"},"end":{"value":93,"modifier":"EXACT"}},"description":"No impact on binding of Fe-S cluster. No impact on binding of Fe-S cluster; when associated with Ala-121 and Ala-127.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26235649"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":121,"modifier":"EXACT"},"end":{"value":121,"modifier":"EXACT"}},"description":"No impact on binding of Fe-S cluster. No impact on binding of Fe-S cluster; when associated with Ala-93 and Ala-127.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26235649"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":127,"modifier":"EXACT"},"end":{"value":127,"modifier":"EXACT"}},"description":"No impact on binding of Fe-S cluster. No impact on binding of Fe-S cluster; when associated with Ala-93 and Ala-121.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26235649"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":142,"modifier":"EXACT"},"end":{"value":142,"modifier":"EXACT"}},"description":"Impaired binding of Fe-S cluster.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26235649"}],"alternativeSequence":{"originalSequence":"C","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":143,"modifier":"EXACT"},"end":{"value":143,"modifier":"EXACT"}},"description":"No impact on binding of Fe-S cluster.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26235649"}],"alternativeSequence":{"originalSequence":"P","alternativeSequences":["A"]}}],"keywords":[{"id":"KW-0001","category":"Ligand","name":"2Fe-2S"},{"id":"KW-0010","category":"Molecular function","name":"Activator"},{"id":"KW-0238","category":"Molecular function","name":"DNA-binding"},{"id":"KW-0408","category":"Ligand","name":"Iron"},{"id":"KW-0411","category":"Ligand","name":"Iron-sulfur"},{"id":"KW-0479","category":"Ligand","name":"Metal-binding"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0678","category":"Molecular function","name":"Repressor"},{"id":"KW-0804","category":"Biological process","name":"Transcription"},{"id":"KW-0805","category":"Biological process","name":"Transcription regulation"}],"references":[{"referenceNumber":1,"citation":{"id":"CI-KSL06CN6861B","citationType":"submission","authors":["Copeland A.","Lucas S.","Lapidus A.","Barry K.","Detter J.C.","Glavina T.","Hammon N.","Israni S.","Pitluck S.","Richardson P.","Mackenzie C.","Choudhary M.","Larimer F.","Hauser L.J.","Land M.","Donohue T.J.","Kaplan S."],"title":"Complete sequence of chromosome 1 of Rhodobacter sphaeroides 2.4.1.","publicationDate":"SEP-2005","submissionDatabase":"EMBL/GenBank/DDBJ databases"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"Proteomes","id":"UP000002703"}],"value":"ATCC 17023 / DSM 158 / JCM 6121 / CCUG 31486 / LMG 2827 / NBRC 12203 / NCIMB 8253 / ATH 2.4.1.","type":"STRAIN"}],"evidences":[{"evidenceCode":"ECO:0000312","source":"Proteomes","id":"UP000002703"}]},{"referenceNumber":2,"citation":{"id":"26235649","citationType":"journal article","authors":["Remes B.","Eisenhardt B.D.","Srinivasan V.","Klug G."],"citationCrossReferences":[{"database":"PubMed","id":"26235649"},{"database":"DOI","id":"10.1002/mbo3.279"}],"title":"IscR of Rhodobacter sphaeroides functions as repressor of genes for iron-sulfur metabolism and represents a new type of iron-sulfur-binding protein.","publicationDate":"2015","journal":"MicrobiologyOpen","firstPage":"790","lastPage":"802","volume":"4"},"referencePositions":["FUNCTION","DNA-BINDING","COFACTOR","DISRUPTION PHENOTYPE","MUTAGENESIS OF HIS-93; 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