{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P0DXU5","uniProtkbId":"DRRA2_STRC4","entryAudit":{"firstPublicDate":"2025-02-05","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2025-02-05","entryVersion":6,"sequenceVersion":1},"annotationScore":4.0,"organism":{"scientificName":"Streptomyces coeruleorubidus","taxonId":116188,"lineage":["Bacteria","Bacillati","Actinomycetota","Actinomycetes","Kitasatosporales","Streptomycetaceae","Streptomyces"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Daunorubicin resistance ATP-binding protein DrrA2"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"39375957"}],"value":"7.6.2.2"}]}},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"39375957"}],"value":"drrA2"},"orfNames":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"WOT35541.1"}],"value":"R5U08_15995"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39375957"},{"evidenceCode":"ECO:0000305"}],"value":"Part of the ABC transporter complex DrrA2B2 involved in daunorubicin efflux (PubMed:39375957). Responsible for energy coupling to the transport system (Probable). Confers self-resistance to daunorubicin, an antibiotic produced by S.coeruleorubidus (PubMed:39375957)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"daunorubicin(in) + ATP + H2O = daunorubicin(out) + ADP + phosphate + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:33147"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:64677"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"7.6.2.2","evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"39375957"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:33148"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"39375957"}]}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"The complex is probably composed of two ATP-binding proteins (DrrA2) and two transmembrane proteins (DrrB2)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P32010"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P32010"}],"value":"Peripheral membrane protein","id":"SL-9903"},"orientation":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P32010"}],"value":"Cytoplasmic side","id":"SL-9910"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.1"}],"value":"Expression is repressed by the HTH-type transcriptional repressor DrrR1 in the absence of daunorubicin"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39375957"}],"value":"Deletion of the drrA2-drrB2 operon decreases by 33% the daunorubicin (DNR) titer in cell culture (PubMed:39375957). The drrA2-drrB2 mutant is more sensitive to DNR (PubMed:39375957). Deletion of the drrA1-drrB1, drrA2-drrB2 and drrA3-drrB3 operons almost blocks DNR production in cell culture, suggesting that disruption of these operons impairs the efflux of DNR, resulting in intracellular accumulation (PubMed:39375957)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the ABC transporter superfamily. Drug exporter-1 (DrugE1) (TC 3.A.1.105) family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":322,"modifier":"EXACT"}},"description":"Daunorubicin resistance ATP-binding protein DrrA2","featureId":"PRO_0000461852"},{"type":"Domain","location":{"start":{"value":6,"modifier":"EXACT"},"end":{"value":236,"modifier":"EXACT"}},"description":"ABC transporter","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00434"}]},{"type":"Binding site","location":{"start":{"value":38,"modifier":"EXACT"},"end":{"value":45,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:30616"}],"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00434"}],"ligand":{"name":"ATP","id":"ChEBI:CHEBI:30616"}}],"keywords":[{"id":"KW-0046","category":"Biological process","name":"Antibiotic resistance"},{"id":"KW-0067","category":"Ligand","name":"ATP-binding"},{"id":"KW-1003","category":"Cellular component","name":"Cell membrane"},{"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"id":"KW-0547","category":"Ligand","name":"Nucleotide-binding"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-1278","category":"Molecular function","name":"Translocase"},{"id":"KW-0813","category":"Biological process","name":"Transport"}],"references":[{"referenceNumber":1,"citation":{"id":"CI-BS666DUH97E3C","citationType":"submission","authors":["Guan W."],"publicationDate":"OCT-2023","submissionDatabase":"EMBL/GenBank/DDBJ databases"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"CICC 11043","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"39375957","citationType":"journal article","authors":["Dong J.","Ning J.","Tian Y.","Li H.","Chen H.","Guan W."],"citationCrossReferences":[{"database":"PubMed","id":"39375957"},{"database":"DOI","id":"10.1111/1751-7915.70023"}],"title":"The involvement of multiple ABC transporters in daunorubicin efflux in Streptomyces coeruleorubidus.","publicationDate":"2024","journal":"Microb. Biotechnol.","firstPage":"e70023","lastPage":"e70023","volume":"17"},"referencePositions":["FUNCTION IN DAUNORUBICIN EFFLUX","INDUCTION","DISRUPTION PHENOTYPE"]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"CP137524","properties":[{"key":"ProteinId","value":"WOT35541.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"RefSeq","id":"WP_193504930.1","properties":[{"key":"NucleotideSequenceId","value":"NZ_BMSO01000006.1"}]},{"database":"AlphaFoldDB","id":"P0DXU5","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"P0DXU5","properties":[{"key":"Description","value":"-"}]},{"database":"Proteomes","id":"UP001305002","properties":[{"key":"Component","value":"Chromosome"}]},{"database":"GO","id":"GO:0005886","properties":[{"key":"GoTerm","value":"C:plasma membrane"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0008559","properties":[{"key":"GoTerm","value":"F:ABC-type xenobiotic transporter activity"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-EC"}]},{"database":"GO","id":"GO:0005524","properties":[{"key":"GoTerm","value":"F:ATP binding"},{"key":"GoEvidenceType","value":"IEA:InterPro"}]},{"database":"GO","id":"GO:0016887","properties":[{"key":"GoTerm","value":"F:ATP hydrolysis activity"},{"key":"GoEvidenceType","value":"IEA:InterPro"}]},{"database":"GO","id":"GO:0043215","properties":[{"key":"GoTerm","value":"P:daunorubicin transport"},{"key":"GoEvidenceType","value":"IEA:InterPro"}]},{"database":"GO","id":"GO:1900753","properties":[{"key":"GoTerm","value":"P:doxorubicin transport"},{"key":"GoEvidenceType","value":"IEA:InterPro"}]},{"database":"FunFam","id":"3.40.50.300:FF:000589","properties":[{"key":"EntryName","value":"ABC transporter, ATP-binding subunit"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"3.40.50.300","properties":[{"key":"EntryName","value":"P-loop containing nucleotide triphosphate hydrolases"},{"key":"MatchStatus","value":"1"}]},{"database":"InterPro","id":"IPR003593","properties":[{"key":"EntryName","value":"AAA+_ATPase"}]},{"database":"InterPro","id":"IPR003439","properties":[{"key":"EntryName","value":"ABC_transporter-like_ATP-bd"}]},{"database":"InterPro","id":"IPR017871","properties":[{"key":"EntryName","value":"ABC_transporter-like_CS"}]},{"database":"InterPro","id":"IPR050763","properties":[{"key":"EntryName","value":"ABC_transporter_ATP-binding"}]},{"database":"InterPro","id":"IPR005894","properties":[{"key":"EntryName","value":"DrrA"}]},{"database":"InterPro","id":"IPR025302","properties":[{"key":"EntryName","value":"DrrA1/2-like_C"}]},{"database":"InterPro","id":"IPR027417","properties":[{"key":"EntryName","value":"P-loop_NTPase"}]},{"database":"NCBIfam","id":"TIGR01188","properties":[{"key":"EntryName","value":"drrA"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR42711","properties":[{"key":"EntryName","value":"ABC TRANSPORTER ATP-BINDING PROTEIN"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR42711:SF19","properties":[{"key":"EntryName","value":"DOXORUBICIN RESISTANCE ATP-BINDING PROTEIN DRRA"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF00005","properties":[{"key":"EntryName","value":"ABC_tran"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF13732","properties":[{"key":"EntryName","value":"DrrA1-3_C"},{"key":"MatchStatus","value":"1"}]},{"database":"SMART","id":"SM00382","properties":[{"key":"EntryName","value":"AAA"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF52540","properties":[{"key":"EntryName","value":"P-loop containing nucleoside triphosphate hydrolases"},{"key":"MatchStatus","value":"1"}]},{"database":"PROSITE","id":"PS00211","properties":[{"key":"EntryName","value":"ABC_TRANSPORTER_1"},{"key":"MatchStatus","value":"1"}]},{"database":"PROSITE","id":"PS50893","properties":[{"key":"EntryName","value":"ABC_TRANSPORTER_2"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MDGYAVRAEAMEKRYGEKRALDGFDLAVGEGTVHGLLGPNGAGKTTAVRILSTLVRLDGGRATVAGLDVARQPREVRARIGLTGQYAAVDEVLTGRQNLEMFGRLFHLGGRRARLRATELLEQFDLTDAGDRGVGKYSGGMRRRLDLAASMILAPAVLFLDEPTTGLDPRSRGEVWESVRALVAGGTTVLLTTQYLEEADKLASRITVIDQGRAIADDTPDGLKNLVGGDRIEVVVAERAEIPRVVKVVARVADGEPEADETESRVHAPVTDRVTALTEVARTLQDEGVRVEDIGLRRPSLDDVFLRLTGHRTENTEAKEAA","length":322,"molWeight":34814,"crc64":"7BF2704DDD048A62","md5":"D91849BBD97F40F0925070A8E161EDC0"},"extraAttributes":{"countByCommentType":{"FUNCTION":1,"CATALYTIC ACTIVITY":1,"SUBUNIT":1,"SUBCELLULAR LOCATION":1,"INDUCTION":1,"DISRUPTION PHENOTYPE":1,"SIMILARITY":1},"countByFeatureType":{"Chain":1,"Domain":1,"Binding site":1},"uniParcId":"UPI0018750DEA"}}