ID   DYR6_PROMI              Reviewed;         157 AA.
AC   P95524;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   02-SEP-2026, entry version 89.
DE   RecName: Full=Dihydrofolate reductase type 6;
DE            EC=1.5.1.3;
DE   AltName: Full=Dihydrofolate reductase type VI;
GN   Name=dhfrVI; Synonyms=dfrVI;
OS   Proteus mirabilis.
OG   Plasmid pUK672.
OC   Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria;
OC   Enterobacterales; Morganellaceae; Proteus.
OX   NCBI_TaxID=584;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=J120;
RX   PubMed=1941991; DOI=10.1099/00222615-35-4-214;
RA   Wylie B.A., Koornhof H.J.;
RT   "Nucleotide sequence of dihydrofolate reductase type VI.";
RL   J. Med. Microbiol. 35:214-218(1991).
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         NADPH + H(+); 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   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; Z86002; CAB06660.1; -; Genomic_DNA.
DR   RefSeq; WP_063844458.1; NG_047734.1.
DR   AlphaFoldDB; P95524; -.
DR   SMR; P95524; -.
DR   CARD; ARO:3004644; Pmir_dfrA6; ARO:0001002; antibiotic target replacement.
DR   KEGG; ag:CAB06660; -.
DR   UniPathway; UPA00077; UER00158.
DR   GO; GO:0005829; C:cytosol; IEA:TreeGrafter.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR   GO; GO:0046452; P:dihydrofolate metabolic process; IEA:TreeGrafter.
DR   GO; GO:0046655; P:folic acid metabolic process; IEA:TreeGrafter.
DR   GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
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   NCBIfam; NF000330; trim_DfrA1_like; 1.
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   3: Inferred from homology;
KW   Antibiotic resistance; Methotrexate resistance; NADP;
KW   One-carbon metabolism; Oxidoreductase; Plasmid; Trimethoprim resistance.
FT   CHAIN           1..157
FT                   /note="Dihydrofolate reductase type 6"
FT                   /id="PRO_0000186423"
FT   DOMAIN          2..156
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
SQ   SEQUENCE   157 AA;  17444 MW;  FE10DDF3724E7D27 CRC64;
     MKISLMAAVS ENGVIGSGLD IPWHVQGEQL LFKAMTYNQW LLVGRKTFDS MGKLPNRKYA
     VVTRSKIISN DPDVVYFASV ESALAYLNNA TAHIFVSGGG EIYKALIDQA DVIHLSVIHK
     HISGDVFFPP VPQGFKQTFE QSFSSNIDYT YQIWAKG
//