ID   DYR_SHV21               Reviewed;         187 AA.
AC   P09503;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1989, sequence version 1.
DT   03-AUG-2022, entry version 103.
DE   RecName: Full=Viral dihydrofolate reductase;
DE            Short=vDHFR;
DE            EC=1.5.1.3;
GN   Name=DHFR; Synonyms=2;
OS   Saimiriine herpesvirus 2 (strain 11) (SaHV-2) (Herpesvirus saimiri).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Herpesviridae; Gammaherpesvirinae; Rhadinovirus.
OX   NCBI_TaxID=10383;
OH   NCBI_TaxID=9521; Saimiri sciureus (Common squirrel monkey).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2830673; DOI=10.1126/science.2830673;
RA   Trimble J.J., Murthy S.C.S., Bakker A., Grassmann R., Desrosiers R.C.;
RT   "A gene for dihydrofolate reductase in a herpesvirus.";
RL   Science 239:1145-1147(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2545905; DOI=10.1128/jvi.63.8.3307-3314.1989;
RA   Murthy S.C.S., Trimble J.J., Desrosiers R.C.;
RT   "Deletion mutants of herpesvirus saimiri define an open reading frame
RT   necessary for transformation.";
RL   J. Virol. 63:3307-3314(1989).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=1321287; DOI=10.1128/jvi.66.8.5047-5058.1992;
RA   Albrecht J.-C., Nicholas J., Biller D., Cameron K.R., Biesinger B.,
RA   Newman C., Wittmann S., Craxton M.A., Coleman H., Fleckenstein B.,
RA   Honess R.W.;
RT   "Primary structure of the herpesvirus saimiri genome.";
RL   J. Virol. 66:5047-5058(1992).
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   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; X64346; CAA45624.1; -; Genomic_DNA.
DR   EMBL; M28071; AAA58726.1; -; Genomic_DNA.
DR   EMBL; M19237; AAA46154.1; -; Genomic_DNA.
DR   RefSeq; NP_040203.1; NC_001350.1.
DR   SMR; P09503; -.
DR   GeneID; 1488256; -.
DR   KEGG; vg:1488256; -.
DR   UniPathway; UPA00077; UER00158.
DR   Proteomes; UP000000587; Genome.
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; -; 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   NADP; One-carbon metabolism; Oxidoreductase; Reference proteome.
FT   CHAIN           1..187
FT                   /note="Viral dihydrofolate reductase"
FT                   /id="PRO_0000186380"
FT   DOMAIN          4..185
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   BINDING         10
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         16..22
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"
SQ   SEQUENCE   187 AA;  21719 MW;  46666EAA3BEA5140 CRC64;
     MVQALNCIVA VAQNMGIGKQ GNLPWPRLMN DFKHFQRMTT TSSVPDKQNL VIMGKKTWFS
     IPEKNRPLKG RINVVLSKEL KELPHRAHFL AKSLDDALKL TEQPELANKV DMVWIIGGSS
     VYKEAMSYPC DLKLFVTRIM QDFECDTFFP EFDLEKYKLL IEYPSVLSNV QEEKSIKYKF
     EVYEKNH