ID   DYR_YEAST               Reviewed;         211 AA.
AC   P07807; D6W2T9;
DT   01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2005, sequence version 2.
DT   27-MAR-2024, entry version 187.
DE   RecName: Full=Dihydrofolate reductase;
DE            EC=1.5.1.3;
GN   Name=DFR1; OrderedLocusNames=YOR236W; ORFNames=O5231;
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].
RX   PubMed=2827121; DOI=10.1093/nar/15.24.10355;
RA   Lagosky P.A., Taylor G.R., Haynes R.H.;
RT   "Molecular characterization of the Saccharomyces cerevisiae dihydrofolate
RT   reductase gene (DFR1).";
RL   Nucleic Acids Res. 15:10355-10371(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2838385; DOI=10.1016/0378-1119(88)90522-7;
RA   Fling M.E., Kopf J., Richards C.A.;
RT   "Nucleotide sequence of the dihydrofolate reductase gene of Saccharomyces
RT   cerevisiae.";
RL   Gene 63:165-174(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2838386; DOI=10.1016/0378-1119(88)90523-9;
RA   Barclay B.J., Huang T., Nagel M.G., Misener V.L., Game J.C., Wahl G.M.;
RT   "Mapping and sequencing of the dihydrofolate reductase gene (DFR1) of
RT   Saccharomyces cerevisiae.";
RL   Gene 63:175-185(1988).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 96604 / S288c / FY1679;
RX   PubMed=8972580;
RX   DOI=10.1002/(sici)1097-0061(199612)12:15%3c1575::aid-yea45%3e3.0.co;2-e;
RA   Boyer J., Michaux G., Fairhead C., Gaillon L., Dujon B.;
RT   "Sequence and analysis of a 26.9 kb fragment from chromosome XV of the
RT   yeast Saccharomyces cerevisiae.";
RL   Yeast 12:1575-1586(1996).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169874;
RA   Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA   Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA   Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA   Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA   Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA   Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA   Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA   Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA   Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA   Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA   Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA   Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA   Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA   Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA   Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA   Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL   Nature 387:98-102(1997).
RN   [6]
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   [7]
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).
CC   -!- FUNCTION: Key enzyme in folate metabolism. Catalyzes an essential
CC       reaction for de novo glycine and purine synthesis, and for DNA
CC       precursor synthesis (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
CC         H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349; EC=1.5.1.3; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU00660};
CC   -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC       tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC   -!- MISCELLANEOUS: Present with 1080 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; Y00887; CAA68779.1; -; Genomic_DNA.
DR   EMBL; M18578; AAB59331.1; -; Genomic_DNA.
DR   EMBL; M26668; AAA34564.1; -; Genomic_DNA.
DR   EMBL; Z75144; CAA99456.1; -; Genomic_DNA.
DR   EMBL; BK006948; DAA11005.1; -; Genomic_DNA.
DR   PIR; JT0269; RDBYD.
DR   RefSeq; NP_014879.1; NM_001183655.1.
DR   AlphaFoldDB; P07807; -.
DR   SMR; P07807; -.
DR   BioGRID; 34628; 470.
DR   DIP; DIP-4120N; -.
DR   IntAct; P07807; 4.
DR   MINT; P07807; -.
DR   STRING; 4932.YOR236W; -.
DR   BindingDB; P07807; -.
DR   ChEMBL; CHEMBL2576; -.
DR   DrugCentral; P07807; -.
DR   MaxQB; P07807; -.
DR   PaxDb; 4932-YOR236W; -.
DR   PeptideAtlas; P07807; -.
DR   EnsemblFungi; YOR236W_mRNA; YOR236W; YOR236W.
DR   GeneID; 854411; -.
DR   KEGG; sce:YOR236W; -.
DR   AGR; SGD:S000005762; -.
DR   SGD; S000005762; DFR1.
DR   VEuPathDB; FungiDB:YOR236W; -.
DR   eggNOG; KOG1324; Eukaryota.
DR   GeneTree; ENSGT00940000168797; -.
DR   HOGENOM; CLU_043966_2_1_1; -.
DR   InParanoid; P07807; -.
DR   OMA; KEMKYFR; -.
DR   OrthoDB; 1118873at2759; -.
DR   BioCyc; YEAST:YOR236W-MONOMER; -.
DR   Reactome; R-SCE-196757; Metabolism of folate and pterines.
DR   UniPathway; UPA00077; UER00158.
DR   BioGRID-ORCS; 854411; 8 hits in 10 CRISPR screens.
DR   PRO; PR:P07807; -.
DR   Proteomes; UP000002311; Chromosome XV.
DR   RNAct; P07807; Protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; IDA:SGD.
DR   GO; GO:0003729; F:mRNA binding; IDA:SGD.
DR   GO; GO:0050661; F:NADP binding; IBA:GO_Central.
DR   GO; GO:0046452; P:dihydrofolate metabolic process; IMP:SGD.
DR   GO; GO:0046655; P:folic acid metabolic process; IBA:GO_Central.
DR   GO; GO:0006545; P:glycine biosynthetic process; IEA:InterPro.
DR   GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IMP:SGD.
DR   CDD; cd00209; DHFR; 1.
DR   Gene3D; 3.40.430.10; Dihydrofolate Reductase, subunit A; 1.
DR   InterPro; IPR012259; DHFR.
DR   InterPro; IPR024072; DHFR-like_dom_sf.
DR   InterPro; IPR017925; DHFR_CS.
DR   InterPro; IPR001796; DHFR_dom.
DR   PANTHER; PTHR48069; DIHYDROFOLATE REDUCTASE; 1.
DR   PANTHER; PTHR48069:SF3; DIHYDROFOLATE REDUCTASE; 1.
DR   Pfam; PF00186; DHFR_1; 1.
DR   PRINTS; PR00070; DHFR.
DR   SUPFAM; SSF53597; Dihydrofolate reductase-like; 1.
DR   PROSITE; PS00075; DHFR_1; 1.
DR   PROSITE; PS51330; DHFR_2; 1.
PE   1: Evidence at protein level;
KW   NADP; One-carbon metabolism; Oxidoreductase; Reference proteome.
FT   CHAIN           1..211
FT                   /note="Dihydrofolate reductase"
FT                   /id="PRO_0000186378"
FT   DOMAIN          7..210
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   BINDING         13
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         20..26
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         34..39
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         58..60
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         74
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         80..82
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         123..130
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        27
FT                   /note="L -> V (in Ref. 1; CAA68779)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   211 AA;  24261 MW;  E030CDE7DA481D5D CRC64;
     MAGGKIPIVG IVACLQPEMG IGFRGGLPWR LPSEMKYFRQ VTSLTKDPNK KNALIMGRKT
     WESIPPKFRP LPNRMNVIIS RSFKDDFVHD KERSIVQSNS LANAIMNLES NFKEHLERIY
     VIGGGEVYSQ IFSITDHWLI TKINPLDKNA TPAMDTFLDA KKLEEVFSEQ DPAQLKEFLP
     PKVELPETDC DQRYSLEEKG YCFEFTLYNR K
//