ID   DYR8_SHISO              Reviewed;         169 AA.
AC   P0ABQ8; Q57452;
DT   08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT   08-NOV-2005, sequence version 1.
DT   25-MAY-2022, entry version 65.
DE   RecName: Full=Dihydrofolate reductase type 8;
DE            EC=1.5.1.3;
DE   AltName: Full=DHFR type IIIC;
DE   AltName: Full=Dihydrofolate reductase type VIII;
GN   Name=dhfrVIII; Synonyms=dhfrIIIc;
OS   Shigella sonnei.
OG   Plasmid pBH700.
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Shigella.
OX   NCBI_TaxID=624;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=7695291; DOI=10.1128/aac.39.1.112;
RA   Barg N.L., Register S., Thomson C., Amyes S.;
RT   "Sequence identity with type VIII and association with IS176 of type IIIc
RT   dihydrofolate reductase from Shigella sonnei.";
RL   Antimicrob. Agents Chemother. 39:112-116(1995).
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. {ECO:0000250}.
CC   -!- MISCELLANEOUS: Confers high-level trimethoprim resistance.
CC   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; U09273; AAA79232.1; -; Genomic_DNA.
DR   RefSeq; WP_000571065.1; NZ_QWTL01000248.1.
DR   AlphaFoldDB; P0ABQ8; -.
DR   SMR; P0ABQ8; -.
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   SUPFAM; SSF53597; SSF53597; 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..169
FT                   /note="Dihydrofolate reductase type 8"
FT                   /id="PRO_0000186426"
FT   DOMAIN          3..169
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
SQ   SEQUENCE   169 AA;  19021 MW;  76E1ABA0C0DE30CC CRC64;
     MIELHAILAA TANGCIGKDN ALPWPPLKGD LARFKKLTMG KVVIMGRKTY ESLPVKLEGR
     TCIVMTRQAL ELPGVRDANG AIFVNNVSDA MRFAQEESVG DVAYVIGGAE IFKRLALMIT
     QIELTFVKRL YEGDTYVDLA EMVKDYEQNG MEEHDLHTYF TYRKKELTE