ID   DYR_BACSU               Reviewed;         168 AA.
AC   P11045;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 2.
DT   27-MAR-2024, entry version 149.
DE   RecName: Full=Dihydrofolate reductase;
DE            EC=1.5.1.3;
GN   Name=dfrA; OrderedLocusNames=BSU21810;
OS   Bacillus subtilis (strain 168).
OC   Bacteria; Bacillota; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX   NCBI_TaxID=224308;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 1-8 AND 166-168.
RC   STRAIN=ATCC 33712 / MI112;
RX   PubMed=2840350; DOI=10.1016/0378-1119(88)90476-3;
RA   Iwakura M., Kawata M., Tsuda K., Tanaka T.;
RT   "Nucleotide sequence of the thymidylate synthase B and dihydrofolate
RT   reductase genes contained in one Bacillus subtilis operon.";
RL   Gene 64:9-20(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=168 / Marburg / ATCC 6051 / DSM 10 / JCM 1465 / NBRC 13719 /
RC   NCIMB 3610 / NRRL NRS-744 / VKM B-501;
RX   PubMed=8969496; DOI=10.1099/13500872-142-11-3005;
RA   Capuano V., Galleron N., Pujic P., Sorokin A., Ehrlich S.D.;
RT   "Organization of the Bacillus subtilis 168 chromosome between kdg and the
RT   attachment site of the SP beta prophage: use of long accurate PCR and yeast
RT   artificial chromosomes for sequencing.";
RL   Microbiology 142:3005-3015(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=168;
RX   PubMed=9384377; DOI=10.1038/36786;
RA   Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA   Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA   Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA   Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA   Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA   Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA   Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA   Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA   Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA   Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA   Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA   Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA   Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA   Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA   Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA   Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA   Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA   Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA   Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA   Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA   Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA   Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA   Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA   Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA   Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA   Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA   Yoshikawa H., Danchin A.;
RT   "The complete genome sequence of the Gram-positive bacterium Bacillus
RT   subtilis.";
RL   Nature 390:249-256(1997).
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   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; M20012; AAA22853.1; -; Genomic_DNA.
DR   EMBL; L77246; AAA96635.1; -; Genomic_DNA.
DR   EMBL; AL009126; CAB14099.1; -; Genomic_DNA.
DR   PIR; JT0291; RDBSD.
DR   RefSeq; NP_390064.1; NC_000964.3.
DR   RefSeq; WP_003230799.1; NZ_JNCM01000036.1.
DR   AlphaFoldDB; P11045; -.
DR   SMR; P11045; -.
DR   STRING; 224308.BSU21810; -.
DR   PaxDb; 224308-BSU21810; -.
DR   EnsemblBacteria; CAB14099; CAB14099; BSU_21810.
DR   GeneID; 939091; -.
DR   KEGG; bsu:BSU21810; -.
DR   PATRIC; fig|224308.179.peg.2383; -.
DR   eggNOG; COG0262; Bacteria.
DR   InParanoid; P11045; -.
DR   OrthoDB; 9804315at2; -.
DR   PhylomeDB; P11045; -.
DR   BioCyc; BSUB:BSU21810-MONOMER; -.
DR   UniPathway; UPA00077; UER00158.
DR   Proteomes; UP000001570; Chromosome.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; IBA:GO_Central.
DR   GO; GO:0050661; F:NADP binding; IBA:GO_Central.
DR   GO; GO:0046452; P:dihydrofolate metabolic process; IBA:GO_Central.
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; IBA:GO_Central.
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   PIRSF; PIRSF000194; DHFR; 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   Direct protein sequencing; NADP; One-carbon metabolism; Oxidoreductase;
KW   Reference proteome.
FT   CHAIN           1..168
FT                   /note="Dihydrofolate reductase"
FT                   /id="PRO_0000186382"
FT   DOMAIN          1..159
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   BINDING         5..7
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         6..7
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         14..19
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         27
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         43..46
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         57
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         62..65
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         95..100
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         114
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   VARIANT         165
FT                   /note="A -> V (in strain: MI112)"
SQ   SEQUENCE   168 AA;  19176 MW;  6E4D11D03F630A44 CRC64;
     MISFIFAMDA NRLIGKDNDL PWHLPNDLAY FKKITSGHSI IMGRKTFESI GRPLPNRKNI
     VVTSAPDSEF QGCTVVSSLK DVLDICSGPE ECFVIGGAQL YTDLFPYADR LYMTKIHHEF
     EGDRHFPEFD ESNWKLVSSE QGTKDEKNPY DYEFLMYEKK NSSKAGGF
//