DYR_BACSU
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 03-AUG-2022, entry version 142.
DE RecName: Full=Dihydrofolate reductase;
DE EC=1.5.1.3;
GN Name=dfrA; OrderedLocusNames=BSU21810;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; 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 / NCIMB
RC 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}.
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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; P11045; -.
DR PRIDE; P11045; -.
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 OMA; EECFVIG; -.
DR PhylomeDB; P11045; -.
DR BioCyc; BSUB:BSU21810-MON; -.
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; -; 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; PTHR48069; 1.
DR Pfam; PF00186; DHFR_1; 1.
DR PIRSF; PIRSF000194; DHFR; 1.
DR SUPFAM; SSF53597; SSF53597; 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
