ID   NNRE_YEAST              Reviewed;         246 AA.
AC   P40165; D6W0Y8;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   04-NOV-2026, entry version 170.
DE   RecName: Full=NAD(P)H-hydrate epimerase {ECO:0000255|HAMAP-Rule:MF_03159};
DE            EC=5.1.99.6 {ECO:0000269|PubMed:21994945};
DE   AltName: Full=NAD(P)HX epimerase {ECO:0000255|HAMAP-Rule:MF_03159};
DE   AltName: Full=Nicotinamide nucleotide repair protein 1 {ECO:0000303|Ref.9};
GN   Name=NNR1 {ECO:0000303|Ref.9}; OrderedLocusNames=YNL200C;
GN   ORFNames=N1370;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 96604 / S288c / FY1679;
RX   PubMed=7725799; DOI=10.1002/yea.320101213;
RA   Jonniaux J.-L., Coster F., Purnelle B., Goffeau A.;
RT   "A 21.7 kb DNA segment on the left arm of yeast chromosome XIV carries
RT   WHI3, GCR2, SPX18, SPX19, an homologue to the heat shock gene SSB1 and 8
RT   new open reading frames of unknown function.";
RL   Yeast 10:1639-1645(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169873; DOI=10.1038/387s093;
RA   Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA   Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA   Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA   Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA   Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA   Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA   Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA   Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA   Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA   Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA   Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA   Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA   Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA   Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA   Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA   Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA   Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT   evolutionary implications.";
RL   Nature 387:93-98(1997).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=17322287; DOI=10.1101/gr.6037607;
RA   Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA   Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA   Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA   Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA   LaBaer J.;
RT   "Approaching a complete repository of sequence-verified protein-encoding
RT   clones for Saccharomyces cerevisiae.";
RL   Genome Res. 17:536-543(2007).
RN   [5]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=14562095; DOI=10.1038/nature02026;
RA   Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA   Weissman J.S., O'Shea E.K.;
RT   "Global analysis of protein localization in budding yeast.";
RL   Nature 425:686-691(2003).
RN   [6]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [7]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=14576278; DOI=10.1073/pnas.2135385100;
RA   Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E.,
RA   Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P.,
RA   Pfanner N., Meisinger C.;
RT   "The proteome of Saccharomyces cerevisiae mitochondria.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003).
RN   [8]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=21994945; DOI=10.1074/jbc.c111.310847;
RA   Marbaix A.Y., Noel G., Detroux A.M., Vertommen D., Van Schaftingen E.,
RA   Linster C.L.;
RT   "Extremely conserved ATP- or ADP-dependent enzymatic system for
RT   nicotinamide nucleotide repair.";
RL   J. Biol. Chem. 286:41246-41252(2011).
RN   [9]
RP   IDENTIFICATION.
RX   DOI=10.1016/j.plgene.2015.11.002;
RA   Firestone K., Awonusi D., Panfair D., Roland D., Ramamurthy A.,
RA   Kusmierczyk A.R.;
RT   "YPL260W, a high-copy suppressor of a copper-sensitive phenotype in yeast,
RT   is linked to DNA repair and proteasome function.";
RL   Plant Gene 5:38-48(2016).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY.
RG   New York structural genomix research consortium (NYSGXRC);
RT   "Crystal structure of yeast hypothetical protein YNU0_yeast.";
RL   Submitted (FEB-2009) to the PDB data bank.
CC   -!- FUNCTION: Catalyzes the epimerization of the S- and R-forms of
CC       NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or
CC       heat-dependent hydration. This is a prerequisite for the S-specific
CC       NAD(P)H-hydrate dehydratase to allow the repair of both epimers of
CC       NAD(P)HX. {ECO:0000255|HAMAP-Rule:MF_03159,
CC       ECO:0000269|PubMed:21994945}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-NADHX = (6S)-NADHX; Xref=Rhea:RHEA:32215,
CC         ChEBI:CHEBI:64074, ChEBI:CHEBI:64075; EC=5.1.99.6;
CC         Evidence={ECO:0000269|PubMed:21994945};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-NADPHX = (6S)-NADPHX; Xref=Rhea:RHEA:32227,
CC         ChEBI:CHEBI:64076, ChEBI:CHEBI:64077; EC=5.1.99.6;
CC         Evidence={ECO:0000269|PubMed:21994945};
CC   -!- COFACTOR:
CC       Name=K(+); Xref=ChEBI:CHEBI:29103; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03159};
CC       Note=Binds 1 potassium ion per subunit. {ECO:0000255|HAMAP-
CC       Rule:MF_03159};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Mitochondrion.
CC   -!- MISCELLANEOUS: Present with 1380 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the NnrE/AIBP family. {ECO:0000255|HAMAP-
CC       Rule:MF_03159}.
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DR   EMBL; X78898; CAA55508.1; -; Genomic_DNA.
DR   EMBL; Z71476; CAA96099.1; -; Genomic_DNA.
DR   EMBL; AY692583; AAT92602.1; -; Genomic_DNA.
DR   EMBL; BK006947; DAA10354.1; -; Genomic_DNA.
DR   PIR; S50731; S50731.
DR   RefSeq; NP_014199.1; NM_001183038.1.
DR   PDB; 1JZT; X-ray; 1.94 A; A/B=1-246.
DR   AlphaFoldDB; P40165; -.
DR   SMR; P40165; -.
DR   BioGRID; 35634; 39.
DR   FunCoup; P40165; 376.
DR   STRING; 4932.YNL200C; -.
DR   PaxDb; 4932-YNL200C; -.
DR   PeptideAtlas; P40165; -.
DR   EnsemblFungi; YNL200C_mRNA; YNL200C; YNL200C.
DR   GeneID; 855521; -.
DR   KEGG; sce:YNL200C; -.
DR   AGR; SGD:S000005144; -.
DR   SGD; S000005144; NNR1.
DR   VEuPathDB; FungiDB:YNL200C; -.
DR   eggNOG; KOG2585; Eukaryota.
DR   HOGENOM; CLU_024853_3_0_1; -.
DR   InParanoid; P40165; -.
DR   OMA; AAMQCPA; -.
DR   OrthoDB; 10064708at2759; -.
DR   BioCyc; YEAST:G3O-33209-MONOMER; -.
DR   Reactome; R-SCE-196807; Nicotinate metabolism.
DR   BioGRID-ORCS; 855521; 1 hit in 10 CRISPR screens.
DR   EvolutionaryTrace; P40165; -.
DR   PRO; PR:P40165; -.
DR   Proteomes; UP000002311; Chromosome XIV.
DR   RNAct; P40165; protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR   GO; GO:0052856; F:NAD(P)HX epimerase activity; IDA:SGD.
DR   GO; GO:0046496; P:nicotinamide nucleotide metabolic process; IDA:SGD.
DR   FunFam; 3.40.50.10260:FF:000005; NAD(P)H-hydrate epimerase; 1.
DR   Gene3D; 3.40.50.10260; YjeF N-terminal domain; 1.
DR   HAMAP; MF_01966; NADHX_epimerase; 1.
DR   InterPro; IPR004443; YjeF_N_dom.
DR   InterPro; IPR036652; YjeF_N_dom_sf.
DR   InterPro; IPR032976; YJEFN_prot_NAXE-like.
DR   NCBIfam; TIGR00197; yjeF_nterm; 1.
DR   PANTHER; PTHR13232; NAD(P)H-HYDRATE EPIMERASE; 1.
DR   PANTHER; PTHR13232:SF10; NAD(P)H-HYDRATE EPIMERASE; 1.
DR   Pfam; PF03853; YjeF_N; 1.
DR   SUPFAM; SSF64153; YjeF N-terminal domain-like; 1.
DR   PROSITE; PS51385; YJEF_N; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Isomerase; Metal-binding; Mitochondrion; NAD;
KW   NADP; Nucleotide-binding; Potassium; Reference proteome.
FT   CHAIN           1..246
FT                   /note="NAD(P)H-hydrate epimerase"
FT                   /id="PRO_0000119061"
FT   DOMAIN          12..234
FT                   /note="YjeF N-terminal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT   BINDING         69..73
FT                   /ligand="(6S)-NADPHX"
FT                   /ligand_id="ChEBI:CHEBI:64076"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT   BINDING         70
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT   BINDING         138
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT   BINDING         142..148
FT                   /ligand="(6S)-NADPHX"
FT                   /ligand_id="ChEBI:CHEBI:64076"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT   BINDING         173
FT                   /ligand="(6S)-NADPHX"
FT                   /ligand_id="ChEBI:CHEBI:64076"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT   BINDING         176
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT   HELIX           9..19
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   TURN            22..24
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   HELIX           28..46
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   HELIX           54..57
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   STRAND          60..65
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   HELIX           69..83
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   STRAND          88..91
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   HELIX           100..111
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   HELIX           124..128
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   TURN            130..132
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   STRAND          133..140
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   HELIX           153..163
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   TURN            164..166
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   STRAND          169..174
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   TURN            180..182
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   STRAND          186..188
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   STRAND          193..200
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   HELIX           203..207
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   TURN            210..212
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   STRAND          214..218
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   HELIX           224..229
FT                   /evidence="ECO:0007829|PDB:1JZT"
FT   STRAND          242..245
FT                   /evidence="ECO:0007829|PDB:1JZT"
SQ   SEQUENCE   246 AA;  27521 MW;  78595E7C92C5E11A CRC64;
     MSTLKVVSSK LAAEIDKELM GPQIGFTLQQ LMELAGFSVA QAVCRQFPLR GKTETEKGKH
     VFVIAGPGNN GGDGLVCARH LKLFGYNPVV FYPKRSERTE FYKQLVHQLN FFKVPVLSQD
     EGNWLEYLKP EKTLCIVDAI FGFSFKPPMR EPFKGIVEEL CKVQNIIPIV SVDVPTGWDV
     DKGPISQPSI NPAVLVSLTV PKPCSSHIRE NQTTHYVGGR FIPRDFANKF GFEPFGYEST
     DQILKL
//