ID   DYR1_ECOLX              Reviewed;         157 AA.
AC   P00382; P13923;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   25-MAY-2022, entry version 131.
DE   RecName: Full=Dihydrofolate reductase type 1;
DE            EC=1.5.1.3;
DE   AltName: Full=Dihydrofolate reductase type I;
DE   AltName: Full=Trimethoprim resistance protein;
GN   Name=dhfrI;
OS   Escherichia coli.
OG   Plasmid IncI1 R483, Plasmid pLMO150, and Plasmid pLMO229.
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=562;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TRANSPOSON=Tn7;
RX   PubMed=6308574; DOI=10.1093/nar/11.15.5147;
RA   Fling M.E., Richards C.;
RT   "The nucleotide sequence of the trimethoprim-resistant dihydrofolate
RT   reductase gene harbored by Tn7.";
RL   Nucleic Acids Res. 11:5147-5158(1983).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   PLASMID=IncI1 R483;
RX   PubMed=3357775; DOI=10.1093/nar/16.5.2235;
RA   Simonsen C.S., Walter M., Levinson A.D.;
RT   "Expression of the plasmid-encoded type I dihydrofolate reductase gene in
RT   cultured mammalian cells: a novel selectable marker.";
RL   Nucleic Acids Res. 16:2235-2246(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   PLASMID=pLMO150, and pLMO229;
RX   PubMed=2188588; DOI=10.1128/aac.34.4.642;
RA   Sundstroem L., Skoeld O.;
RT   "The dhfrI trimethoprim resistance gene of Tn7 can be found at specific
RT   sites in other genetic surroundings.";
RL   Antimicrob. Agents Chemother. 34:642-650(1990).
RN   [4]
RP   PROTEIN SEQUENCE OF 1-34.
RC   PLASMID=IncI1 R483;
RX   PubMed=6350298; DOI=10.1016/s0021-9258(17)44369-9;
RA   Novak P., Stone D., Burchall J.J.;
RT   "R plasmid dihydrofolate reductase with a dimeric subunit structure.";
RL   J. Biol. Chem. 258:10956-10959(1983).
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   -!- SUBUNIT: Homodimer.
CC   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; X00926; CAA25445.1; -; Genomic_DNA.
DR   EMBL; X17477; CAA35509.1; -; Genomic_DNA.
DR   EMBL; X17478; CAA35512.1; -; Genomic_DNA.
DR   PIR; S03651; RDECD7.
DR   RefSeq; NP_065309.1; NC_002525.1.
DR   RefSeq; WP_000777554.1; NZ_WWEV01000054.1.
DR   RefSeq; YP_004422906.1; NC_015472.1.
DR   RefSeq; YP_190212.1; NC_006671.1.
DR   AlphaFoldDB; P00382; -.
DR   SMR; P00382; -.
DR   BindingDB; P00382; -.
DR   ChEMBL; CHEMBL2627; -.
DR   DrugCentral; P00382; -.
DR   GeneID; 58164746; -.
DR   KEGG; ag:CAA25445; -.
DR   UniPathway; UPA00077; UER00158.
DR   PRO; PR:P00382; -.
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:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR   GO; GO:0031427; P:response to methotrexate; 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   SUPFAM; SSF53597; SSF53597; 1.
DR   PROSITE; PS00075; DHFR_1; 1.
DR   PROSITE; PS51330; DHFR_2; 1.
PE   1: Evidence at protein level;
KW   Antibiotic resistance; Direct protein sequencing; Methotrexate resistance;
KW   NADP; One-carbon metabolism; Oxidoreductase; Plasmid; Transposable element;
KW   Trimethoprim resistance.
FT   CHAIN           1..157
FT                   /note="Dihydrofolate reductase type 1"
FT                   /id="PRO_0000186420"
FT   DOMAIN          2..156
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   VARIANT         75
FT                   /note="L -> V (in plasmid pLMO229)"
SQ   SEQUENCE   157 AA;  17575 MW;  487F818A40E4991B CRC64;
     MKLSLMVAIS KNGVIGNGPD IPWSAKGEQL LFKAITYNQW LLVGRKTFES MGALPNRKYA
     VVTRSSFTSD NENVLIFPSI KDALTNLKKI TDHVIVSGGG EIYKSLIDQV DTLHISTIDI
     EPEGDVYFPE IPSNFRPVFT QDFASNINYS YQIWQKG