ID   DYR3_SALTM              Reviewed;         162 AA.
AC   P12833;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1989, sequence version 1.
DT   25-MAY-2022, entry version 98.
DE   RecName: Full=Dihydrofolate reductase type 3;
DE            EC=1.5.1.3;
DE   AltName: Full=Dihydrofolate reductase type III;
GN   Name=dhfrIII;
OS   Salmonella typhimurium.
OG   Plasmid pAZ1.
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Salmonella.
OX   NCBI_TaxID=90371;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2840679; DOI=10.1016/0147-619x(88)90060-1;
RA   Fling M.E., Kopf J., Richards C.;
RT   "Characterization of plasmid pAZ1 and the type III dihydrofolate reductase
RT   gene.";
RL   Plasmid 19:30-38(1988).
RN   [2]
RP   PROTEIN SEQUENCE OF 1-21.
RX   PubMed=6371010; DOI=10.1016/s0021-9258(18)91094-x;
RA   Joyner S.S., Fling M.E., Stone D., Baccanari D.P.;
RT   "Characterization of an R-plasmid dihydrofolate reductase with a monomeric
RT   structure.";
RL   J. Biol. Chem. 259:5851-5856(1984).
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: Monomer.
CC   -!- MISCELLANEOUS: The plasmid pAZ1 determines trimethoprim and
CC       sulphonamide resistance.
CC   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; J03306; AAA25550.1; -; Genomic_DNA.
DR   PIR; B22241; B22241.
DR   PIR; JT0266; RDEBDT.
DR   AlphaFoldDB; P12833; -.
DR   SMR; P12833; -.
DR   KEGG; ag:AAA25550; -.
DR   UniPathway; UPA00077; UER00158.
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   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   Antibiotic resistance; Direct protein sequencing; Methotrexate resistance;
KW   NADP; One-carbon metabolism; Oxidoreductase; Plasmid;
KW   Trimethoprim resistance.
FT   CHAIN           1..162
FT                   /note="Dihydrofolate reductase type 3"
FT                   /id="PRO_0000186421"
FT   DOMAIN          2..160
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   CONFLICT        8
FT                   /note="A -> S (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   162 AA;  18033 MW;  199343AE8675FDED CRC64;
     MLISLIAALA HNNLIGKDNL IPWHLPADLR HFKAVTLGKP VVMGRRTFES IGRPLPGRRN
     VVVSRNPQWQ AEGVEVAPSL DAALALLTDC EEAMIIGGGQ LYAEALPRAD RLYLTYIDAQ
     LNGDTHFPDY LSLGWQELER STHPADDKNS YACEFVTLSR QR