ID   DRTS_PLAVN              Reviewed;         182 AA.
AC   P46103;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   02-SEP-2026, entry version 95.
DE   RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase;
DE            Short=DHFR-TS;
DE   Includes:
DE     RecName: Full=Dihydrofolate reductase;
DE              EC=1.5.1.3;
DE   Includes:
DE     RecName: Full=Thymidylate synthase;
DE              EC=2.1.1.45;
DE   Flags: Fragment;
OS   Plasmodium vinckei.
OC   Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC   Plasmodiidae; Plasmodium; Vinckeia.
OX   NCBI_TaxID=5860;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=7969277; DOI=10.1016/0166-6851(94)90087-6;
RA   Cheng Q., Saul A.;
RT   "The dihydrofolate reductase domain of rodent malarias: point mutations and
RT   pyrimethamine resistance.";
RL   Mol. Biochem. Parasitol. 65:361-363(1994).
CC   -!- FUNCTION: Bifunctional enzyme. Involved in de novo dTMP biosynthesis.
CC       Key enzyme in folate metabolism. Catalyzes an essential reaction for de
CC       novo glycine and purine synthesis, DNA precursor synthesis, and for the
CC       conversion of dUMP to dTMP (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
CC         NADPH + H(+); 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   -!- CATALYTIC ACTIVITY:
CC       Reaction=dUMP + (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate = 7,8-
CC         dihydrofolate + dTMP; Xref=Rhea:RHEA:12104, ChEBI:CHEBI:15636,
CC         ChEBI:CHEBI:57451, ChEBI:CHEBI:63528, ChEBI:CHEBI:246422;
CC         EC=2.1.1.45;
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   -!- SIMILARITY: In the N-terminal section; belongs to the dihydrofolate
CC       reductase family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the thymidylate
CC       synthase family. {ECO:0000305}.
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DR   EMBL; L28121; AAA29582.1; -; Genomic_DNA.
DR   AlphaFoldDB; P46103; -.
DR   SMR; P46103; -.
DR   VEuPathDB; PlasmoDB:PVBDA_0701980; -.
DR   VEuPathDB; PlasmoDB:PVLDE_0703080; -.
DR   VEuPathDB; PlasmoDB:PVPCR_0702010; -.
DR   VEuPathDB; PlasmoDB:PVSEL_0702080; -.
DR   VEuPathDB; PlasmoDB:PVVCY_0701900; -.
DR   VEuPathDB; PlasmoDB:YYE_04219; -.
DR   VEuPathDB; PlasmoDB:YYG_04095; -.
DR   UniPathway; UPA00077; UER00158.
DR   GO; GO:0005739; C:mitochondrion; IEA:TreeGrafter.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR   GO; GO:0004799; F:thymidylate synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046452; P:dihydrofolate metabolic process; IEA:TreeGrafter.
DR   GO; GO:0046655; P:folic acid metabolic process; IEA:TreeGrafter.
DR   GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR   CDD; cd00209; DHFR; 1.
DR   FunFam; 3.40.430.10:FF:000007; Bifunctional dihydrofolate reductase-thymidylate synthase; 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   3: Inferred from homology;
KW   Methyltransferase; Multifunctional enzyme; NADP; Nucleotide biosynthesis;
KW   One-carbon metabolism; Oxidoreductase; Transferase.
FT   CHAIN           <1..>182
FT                   /note="Bifunctional dihydrofolate reductase-thymidylate
FT                   synthase"
FT                   /id="PRO_0000186350"
FT   DOMAIN          <1..>182
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   BINDING         25..31
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         40
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         93..95
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         114..117
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         154
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         155..162
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         160
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         175
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   NON_TER         1
FT   NON_TER         182
SQ   SEQUENCE   182 AA;  20925 MW;  33CCD27441763198 CRC64;
     AICACCKVLN SNEKASCFSN KTFKGLGNAG GLPWKCNSVD MKHFVSVTSY VNENNYIRLK
     WKRDKYIKEN NVKVNTDGIP SIDKLQNIVV MGKTSWESIP SKFKPLENRI NIILSRTLKK
     ENLAKEYSNV IIIKSVDELF PILKCIKYYK CFIIGGASVY KEFLDRNLIK KIYFTRINNA
     YT
//