ID   DYR_HELVI               Reviewed;         185 AA.
AC   Q9U8B8;
DT   15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   22-FEB-2023, entry version 85.
DE   RecName: Full=Dihydrofolate reductase;
DE            EC=1.5.1.3;
GN   Name=DHFR;
OS   Heliothis virescens (Tobacco budworm moth).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Lepidoptera; Glossata; Ditrysia; Noctuoidea;
OC   Noctuidae; Heliothinae; Heliothis.
OX   NCBI_TaxID=7102 {ECO:0000312|EMBL:AAF04459.1};
RN   [1] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 3-22; 32-38; 143-149;
RP   153-159 AND 170-175, AND ACTIVITY REGULATION.
RC   TISSUE=Larva;
RX   PubMed=10632709; DOI=10.1046/j.1432-1327.2000.01009.x;
RA   Walker V.K., Tyshenko M.G., Kuiper M.J., Dargar R.V., Yuhas D.A.,
RA   Cruickshank P.A., Chaguturu R.;
RT   "Tobacco budworm dihydrofolate reductase is a promising target for
RT   insecticide discovery.";
RL   Eur. J. Biochem. 267:394-403(2000).
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;
CC         Evidence={ECO:0000250|UniProtKB:P28019, ECO:0000255|PROSITE-
CC         ProRule:PRU00660};
CC   -!- ACTIVITY REGULATION: Activated by dithiothreitol and p-
CC       chloromercuribenzoate. Inhibited by trimethoprim, methotrexate, sodium
CC       tetrathionate and hydroxymercuribenzoate.
CC       {ECO:0000269|PubMed:10632709}.
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}.
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DR   EMBL; AF104106; AAF04459.1; -; mRNA.
DR   AlphaFoldDB; Q9U8B8; -.
DR   SMR; Q9U8B8; -.
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: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   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   1: Evidence at protein level;
KW   Direct protein sequencing; NADP; One-carbon metabolism; Oxidoreductase.
FT   CHAIN           1..185
FT                   /note="Dihydrofolate reductase"
FT                   /id="PRO_0000186371"
FT   DOMAIN          5..184
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   BINDING         11
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         17..23
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         31..36
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         55..57
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         71
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         77..79
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         117..124
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        5
FT                   /note="K -> L (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        7
FT                   /note="N -> D (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        11..13
FT                   /note="AAC -> IFD (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        15
FT                   /note="N -> D (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        21
FT                   /note="N -> D (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        158
FT                   /note="H -> Q (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   185 AA;  21089 MW;  9B8C0E50ED175812 CRC64;
     MSQVKLNLIA AACDNMGIGV NGALPWRLKK EMAYFTTMTS KVSEPTKVNA VIMGRRTWDC
     IPDKYRPLQD RVNIVLTHNV DSVKENVPEG VMVFPGLDEA IKYIEGREDI ESTWVIGGSS
     IYRAAMTHPN CGKIYLTEIQ KSFDCDTFFP NIDKQQFHLV DEEQIPGEKQ VEGNISYYFR
     VYKKL
//