ID   DYR_STAEQ               Reviewed;         161 AA.
AC   Q5HPB1;
DT   08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT   15-FEB-2005, sequence version 1.
DT   03-AUG-2022, entry version 100.
DE   RecName: Full=Dihydrofolate reductase;
DE            Short=DHFR;
DE            EC=1.5.1.3;
GN   Name=folA; Synonyms=dfrC, folA1; OrderedLocusNames=SERP1002;
OS   Staphylococcus epidermidis (strain ATCC 35984 / RP62A).
OC   Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=176279;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 35984 / RP62A;
RX   PubMed=15774886; DOI=10.1128/jb.187.7.2426-2438.2005;
RA   Gill S.R., Fouts D.E., Archer G.L., Mongodin E.F., DeBoy R.T., Ravel J.,
RA   Paulsen I.T., Kolonay J.F., Brinkac L.M., Beanan M.J., Dodson R.J.,
RA   Daugherty S.C., Madupu R., Angiuoli S.V., Durkin A.S., Haft D.H.,
RA   Vamathevan J.J., Khouri H., Utterback T.R., Lee C., Dimitrov G., Jiang L.,
RA   Qin H., Weidman J., Tran K., Kang K.H., Hance I.R., Nelson K.E.,
RA   Fraser C.M.;
RT   "Insights on evolution of virulence and resistance from the complete genome
RT   analysis of an early methicillin-resistant Staphylococcus aureus strain and
RT   a biofilm-producing methicillin-resistant Staphylococcus epidermidis
RT   strain.";
RL   J. Bacteriol. 187:2426-2438(2005).
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; CP000029; AAW54371.1; -; Genomic_DNA.
DR   RefSeq; WP_001830952.1; NC_002976.3.
DR   AlphaFoldDB; Q5HPB1; -.
DR   SMR; Q5HPB1; -.
DR   STRING; 176279.SERP1002; -.
DR   EnsemblBacteria; AAW54371; AAW54371; SERP1002.
DR   GeneID; 50018758; -.
DR   KEGG; ser:SERP1002; -.
DR   eggNOG; COG0262; Bacteria.
DR   HOGENOM; CLU_043966_5_1_9; -.
DR   OMA; RDNQLPW; -.
DR   OrthoDB; 1920912at2; -.
DR   UniPathway; UPA00077; UER00158.
DR   Proteomes; UP000000531; Chromosome.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0050661; F:NADP binding; IEA:InterPro.
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; IEA:UniProtKB-UniPathway.
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   3: Inferred from homology;
KW   NADP; One-carbon metabolism; Oxidoreductase; Reference proteome.
FT   CHAIN           1..161
FT                   /note="Dihydrofolate reductase"
FT                   /id="PRO_0000186415"
FT   DOMAIN          2..157
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   BINDING         6..8
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         7..8
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         15..20
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         28
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         44..47
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         58
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         63..66
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         93..98
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         112
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   161 AA;  18417 MW;  CB3167940A387EE0 CRC64;
     MTLSIIVAHD KQRVIGYQNQ LPWHLPNDLK HVKQLTTGNT LVMGRKTFNS IGKPLPNRRN
     VVLTNQASFH HEGVDVINSL DEIKELSGHV FIFGGQTLFE AMIDQVDDMY ITVIDGKFQG
     DTFFPPYTFE NWEVESSVEG QLDEKNTIPH TFLHLVRRKG K