{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"O67377","uniProtkbId":"NNR_AQUAE","entryAudit":{"firstPublicDate":"2012-03-21","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1998-08-01","entryVersion":120,"sequenceVersion":1},"annotationScore":3.0,"organism":{"scientificName":"Aquifex aeolicus (strain VF5)","taxonId":224324,"lineage":["Bacteria","Pseudomonadati","Aquificota","Aquificia","Aquificales","Aquificaceae","Aquifex"]},"proteinExistence":"3: Inferred from homology","proteinDescription":{"recommendedName":{"fullName":{"value":"Bifunctional NAD(P)H-hydrate repair enzyme Nnr"}},"alternativeNames":[{"fullName":{"value":"Nicotinamide nucleotide repair protein"}}],"includes":[{"recommendedName":{"fullName":{"value":"ADP-dependent (S)-NAD(P)H-hydrate dehydratase"},"ecNumbers":[{"value":"4.2.1.136"}]},"alternativeNames":[{"fullName":{"value":"ADP-dependent NAD(P)HX dehydratase"}}]},{"recommendedName":{"fullName":{"value":"NAD(P)H-hydrate epimerase"},"ecNumbers":[{"value":"5.1.99.6"}]},"alternativeNames":[{"fullName":{"value":"NAD(P)HX epimerase"}}]}]},"genes":[{"geneName":{"value":"nnr"},"orderedLocusNames":[{"value":"aq_1365"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Bifunctional enzyme that catalyzes the epimerization of the S- and R-forms of NAD(P)HX and the dehydration of the S-form of NAD(P)HX at the expense of ADP, which is converted to AMP. This allows the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration (By similarity)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"(6S)-NADHX + ADP = AMP + phosphate + NADH + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:32223"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:57945"},{"database":"ChEBI","id":"CHEBI:64074"},{"database":"ChEBI","id":"CHEBI:456215"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"4.2.1.136"}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"(6S)-NADPHX + ADP = AMP + phosphate + NADPH + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:32235"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:57783"},{"database":"ChEBI","id":"CHEBI:64076"},{"database":"ChEBI","id":"CHEBI:456215"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"4.2.1.136"}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"(6R)-NADHX = (6S)-NADHX","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:32215"},{"database":"ChEBI","id":"CHEBI:64074"},{"database":"ChEBI","id":"CHEBI:64075"}],"ecNumber":"5.1.99.6"}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"(6R)-NADPHX = (6S)-NADPHX","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:32227"},{"database":"ChEBI","id":"CHEBI:64076"},{"database":"ChEBI","id":"CHEBI:64077"}],"ecNumber":"5.1.99.6"}},{"commentType":"COFACTOR","cofactors":[{"name":"K(+)","evidences":[{"evidenceCode":"ECO:0000250"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29103"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Binds 1 potassium ion per subunit."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"In the N-terminal section; belongs to the NnrE/AIBP family"}],"commentType":"SIMILARITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"In the C-terminal section; belongs to the NnrD/CARKD family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":499,"modifier":"EXACT"}},"description":"Bifunctional NAD(P)H-hydrate repair enzyme Nnr","featureId":"PRO_0000416414"},{"type":"Domain","location":{"start":{"value":9,"modifier":"EXACT"},"end":{"value":208,"modifier":"EXACT"}},"description":"YjeF N-terminal"},{"type":"Domain","location":{"start":{"value":214,"modifier":"EXACT"},"end":{"value":496,"modifier":"EXACT"}},"description":"YjeF C-terminal"},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":208,"modifier":"EXACT"}},"description":"NAD(P)H-hydrate epimerase","evidences":[{"evidenceCode":"ECO:0000250"}]},{"type":"Region","location":{"start":{"value":57,"modifier":"EXACT"},"end":{"value":61,"modifier":"EXACT"}},"description":"NADPHX 1; for epimerase activity","evidences":[{"evidenceCode":"ECO:0000250"}]},{"type":"Region","location":{"start":{"value":122,"modifier":"EXACT"},"end":{"value":128,"modifier":"EXACT"}},"description":"NADPHX 1; for epimerase activity","evidences":[{"evidenceCode":"ECO:0000250"}]},{"type":"Region","location":{"start":{"value":216,"modifier":"EXACT"},"end":{"value":499,"modifier":"EXACT"}},"description":"ADP-dependent (S)-NAD(P)H-hydrate dehydratase","evidences":[{"evidenceCode":"ECO:0000250"}]},{"type":"Region","location":{"start":{"value":371,"modifier":"EXACT"},"end":{"value":377,"modifier":"EXACT"}},"description":"NADPHX 2; for dehydratase activity","evidences":[{"evidenceCode":"ECO:0000250"}]},{"type":"Binding site","location":{"start":{"value":58,"modifier":"EXACT"},"end":{"value":58,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29103"}],"evidences":[{"evidenceCode":"ECO:0000250"}],"ligand":{"name":"K(+)","id":"ChEBI:CHEBI:29103"}},{"type":"Binding site","location":{"start":{"value":118,"modifier":"EXACT"},"end":{"value":118,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29103"}],"evidences":[{"evidenceCode":"ECO:0000250"}],"ligand":{"name":"K(+)","id":"ChEBI:CHEBI:29103"}},{"type":"Binding site","location":{"start":{"value":151,"modifier":"EXACT"},"end":{"value":151,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:64076"}],"evidences":[{"evidenceCode":"ECO:0000250"}],"ligand":{"name":"(6S)-NADPHX","id":"ChEBI:CHEBI:64076","label":"1","note":"for epimerase activity"}},{"type":"Binding site","location":{"start":{"value":154,"modifier":"EXACT"},"end":{"value":154,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29103"}],"evidences":[{"evidenceCode":"ECO:0000250"}],"ligand":{"name":"K(+)","id":"ChEBI:CHEBI:29103"}},{"type":"Binding site","location":{"start":{"value":318,"modifier":"EXACT"},"end":{"value":318,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:64076"}],"evidences":[{"evidenceCode":"ECO:0000250"}],"ligand":{"name":"(6S)-NADPHX","id":"ChEBI:CHEBI:64076","label":"2","note":"for dehydratase activity"}},{"type":"Binding site","location":{"start":{"value":408,"modifier":"EXACT"},"end":{"value":412,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:456216"}],"evidences":[{"evidenceCode":"ECO:0000250"}],"ligand":{"name":"ADP","id":"ChEBI:CHEBI:456216"}},{"type":"Binding site","location":{"start":{"value":428,"modifier":"EXACT"},"end":{"value":437,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:456216"}],"evidences":[{"evidenceCode":"ECO:0000250"}],"ligand":{"name":"ADP","id":"ChEBI:CHEBI:456216"}},{"type":"Binding site","location":{"start":{"value":438,"modifier":"EXACT"},"end":{"value":438,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:64076"}],"evidences":[{"evidenceCode":"ECO:0000250"}],"ligand":{"name":"(6S)-NADPHX","id":"ChEBI:CHEBI:64076","label":"2","note":"for dehydratase activity"}}],"keywords":[{"id":"KW-0067","category":"Ligand","name":"ATP-binding"},{"id":"KW-0413","category":"Molecular function","name":"Isomerase"},{"id":"KW-0456","category":"Molecular function","name":"Lyase"},{"id":"KW-0479","category":"Ligand","name":"Metal-binding"},{"id":"KW-0511","category":"Molecular function","name":"Multifunctional enzyme"},{"id":"KW-0520","category":"Ligand","name":"NAD"},{"id":"KW-0521","category":"Ligand","name":"NADP"},{"id":"KW-0547","category":"Ligand","name":"Nucleotide-binding"},{"id":"KW-0630","category":"Ligand","name":"Potassium"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"}],"references":[{"referenceNumber":1,"citation":{"id":"9537320","citationType":"journal article","authors":["Deckert G.","Warren P.V.","Gaasterland T.","Young W.G.","Lenox A.L.","Graham D.E.","Overbeek R.","Snead M.A.","Keller M.","Aujay M.","Huber R.","Feldman R.A.","Short J.M.","Olsen G.J.","Swanson R.V."],"citationCrossReferences":[{"database":"PubMed","id":"9537320"},{"database":"DOI","id":"10.1038/32831"}],"title":"The complete genome of the hyperthermophilic bacterium Aquifex aeolicus.","publicationDate":"1998","journal":"Nature","firstPage":"353","lastPage":"358","volume":"392"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"VF5","type":"STRAIN"}]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"AE000657","properties":[{"key":"ProteinId","value":"AAC07340.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"PIR","id":"F70418","properties":[{"key":"EntryName","value":"F70418"}]},{"database":"RefSeq","id":"WP_010880879.1","properties":[{"key":"NucleotideSequenceId","value":"NC_000918.1"}]},{"database":"AlphaFoldDB","id":"O67377","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"O67377","properties":[{"key":"Description","value":"-"}]},{"database":"FunCoup","id":"O67377","properties":[{"key":"Number of interactors","value":"242"}]},{"database":"STRING","id":"224324.aq_1365","properties":[{"key":"Description","value":"-"}]},{"database":"EnsemblBacteria","id":"AAC07340","properties":[{"key":"ProteinId","value":"AAC07340"},{"key":"GeneId","value":"aq_1365"}]},{"database":"KEGG","id":"aae:aq_1365","properties":[{"key":"Description","value":"-"}]},{"database":"PATRIC","id":"fig|224324.8.peg.1068","properties":[{"key":"GeneDesignation","value":"-"}]},{"database":"eggNOG","id":"COG0062","properties":[{"key":"ToxonomicScope","value":"Bacteria"}]},{"database":"eggNOG","id":"COG0063","properties":[{"key":"ToxonomicScope","value":"Bacteria"}]},{"database":"HOGENOM","id":"CLU_024853_4_1_0","properties":[{"key":"Description","value":"-"}]},{"database":"InParanoid","id":"O67377","properties":[{"key":"Description","value":"-"}]},{"database":"OrthoDB","id":"9806925at2","properties":[{"key":"Description","value":"-"}]},{"database":"Proteomes","id":"UP000000798","properties":[{"key":"Component","value":"Chromosome"}]},{"database":"GO","id":"GO:0052855","properties":[{"key":"GoTerm","value":"F:ADP-dependent NAD(P)H-hydrate dehydratase activity"},{"key":"GoEvidenceType","value":"IBA:GO_Central"}]},{"database":"GO","id":"GO:0052856","properties":[{"key":"GoTerm","value":"F:NAD(P)HX epimerase activity"},{"key":"GoEvidenceType","value":"IBA:GO_Central"}]},{"database":"GO","id":"GO:0110051","properties":[{"key":"GoTerm","value":"P:metabolite repair"},{"key":"GoEvidenceType","value":"IBA:GO_Central"}]},{"database":"GO","id":"GO:0046496","properties":[{"key":"GoTerm","value":"P:nicotinamide nucleotide metabolic process"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-UniRule"}]},{"database":"CDD","id":"cd01171","properties":[{"key":"EntryName","value":"YXKO-related"},{"key":"MatchStatus","value":"1"}]},{"database":"FunFam","id":"3.40.50.10260:FF:000003","properties":[{"key":"EntryName","value":"Multifunctional fusion protein"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"3.40.1190.20","properties":[{"key":"EntryName","value":"-"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"3.40.50.10260","properties":[{"key":"EntryName","value":"YjeF N-terminal domain"},{"key":"MatchStatus","value":"1"}]},{"database":"HAMAP","id":"MF_01965","properties":[{"key":"EntryName","value":"NADHX_dehydratase"},{"key":"MatchStatus","value":"1"}]},{"database":"HAMAP","id":"MF_01966","properties":[{"key":"EntryName","value":"NADHX_epimerase"},{"key":"MatchStatus","value":"1"}]},{"database":"InterPro","id":"IPR017953","properties":[{"key":"EntryName","value":"Carbohydrate_kinase_pred_CS"}]},{"database":"InterPro","id":"IPR000631","properties":[{"key":"EntryName","value":"CARKD"}]},{"database":"InterPro","id":"IPR030677","properties":[{"key":"EntryName","value":"Nnr"}]},{"database":"InterPro","id":"IPR029056","properties":[{"key":"EntryName","value":"Ribokinase-like"}]},{"database":"InterPro","id":"IPR004443","properties":[{"key":"EntryName","value":"YjeF_N_dom"}]},{"database":"InterPro","id":"IPR036652","properties":[{"key":"EntryName","value":"YjeF_N_dom_sf"}]},{"database":"NCBIfam","id":"TIGR00196","properties":[{"key":"EntryName","value":"yjeF_cterm"},{"key":"MatchStatus","value":"1"}]},{"database":"NCBIfam","id":"TIGR00197","properties":[{"key":"EntryName","value":"yjeF_nterm"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR12592:SF0","properties":[{"key":"EntryName","value":"ATP-DEPENDENT (S)-NAD(P)H-HYDRATE DEHYDRATASE"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR12592","properties":[{"key":"EntryName","value":"ATP-DEPENDENT (S)-NAD(P)H-HYDRATE DEHYDRATASE FAMILY MEMBER"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF01256","properties":[{"key":"EntryName","value":"Carb_kinase"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF03853","properties":[{"key":"EntryName","value":"YjeF_N"},{"key":"MatchStatus","value":"1"}]},{"database":"PIRSF","id":"PIRSF017184","properties":[{"key":"EntryName","value":"Nnr"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF53613","properties":[{"key":"EntryName","value":"Ribokinase-like"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF64153","properties":[{"key":"EntryName","value":"YjeF N-terminal domain-like"},{"key":"MatchStatus","value":"1"}]},{"database":"PROSITE","id":"PS01050","properties":[{"key":"EntryName","value":"YJEF_C_2"},{"key":"MatchStatus","value":"1"}]},{"database":"PROSITE","id":"PS51383","properties":[{"key":"EntryName","value":"YJEF_C_3"},{"key":"MatchStatus","value":"1"}]},{"database":"PROSITE","id":"PS51385","properties":[{"key":"EntryName","value":"YJEF_N"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MKILKAHEMSSIDNKTIEEIGIPSLVLMENASKGVFENIRKYFPDAKNILVVAGKGNNGGDGLALARHLYLNGFSVDIFLAFGEVKGDAKTQLEILKKIGIEPLKKKPDFKEYDLIVDAIFGTGFQPPVKGEVANLIKEINNSSVPIVSIDIPSGLSADTGESFEPSVKADLTVTFQFPKICHYLYPAAKKCGKVEVVDISIPEFLAKDVKRDLLRKSDLKPYKREPDTYKTKEGSVLLVGGSVGKTGAVIMSAKAASRAGAGLVTVGIPRELNPIFESLLIEEMSLPLSGTSRLSVFCVEEILELKDRFHALGIGMGMDRYEEGQDIVISLLEKWEKPILIDADGINNLADYGDYTPLKDREIPAVLTPHIGEFSRLTGYDTKTITYNQIDIAQEFSEKNRCYLVLKGARTVISTPDGRAYLFADGTPALAKGGTGDVLAGILTALIAKMDTEEALKLGVYLHGLAGKVAEKKLHTESVKATDVTESLPEAFREIYVN","length":499,"molWeight":54372,"crc64":"EDDB6B5230AC50F3","md5":"5E109DBCCD1FA40ED8951EF742EAEE1A"},"extraAttributes":{"countByCommentType":{"FUNCTION":1,"CATALYTIC ACTIVITY":4,"COFACTOR":1,"SIMILARITY":2},"countByFeatureType":{"Chain":1,"Domain":2,"Region":5,"Binding site":8},"uniParcId":"UPI00000565DA"}}