ID   B9PR34_TOXGV            Unreviewed;       610 AA.
AC   B9PR34; B6KHC9; B9QD29; S7V0S8; S8ENZ2;
DT   24-MAR-2009, integrated into UniProtKB/TrEMBL.
DT   24-MAR-2009, sequence version 1.
DT   02-SEP-2026, entry version 102.
DE   RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase {ECO:0000256|ARBA:ARBA00019798, ECO:0000256|PIRNR:PIRNR000389};
GN   ORFNames=TGVEG_249180 {ECO:0000313|EMBL:ESS34444.1};
OS   Toxoplasma gondii (strain ATCC 50861 / VEG).
OC   Eukaryota; Sar; Alveolata; Apicomplexa; Conoidasida; Coccidia;
OC   Eucoccidiorida; Eimeriorina; Sarcocystidae; Toxoplasma.
OX   NCBI_TaxID=432359 {ECO:0000313|EMBL:ESS34444.1, ECO:0000313|Proteomes:UP000002226};
RN   [1] {ECO:0000313|EMBL:ESS34444.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=VEG {ECO:0000313|EMBL:ESS34444.1};
RA   Paulsen I.;
RL   Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
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. {ECO:0000256|ARBA:ARBA00025154}.
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;
CC         Evidence={ECO:0000256|ARBA:ARBA00048873, ECO:0000256|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; Evidence={ECO:0000256|ARBA:ARBA00047344};
CC   -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC       tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC       {ECO:0000256|ARBA:ARBA00004903, ECO:0000256|PIRNR:PIRNR000389}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the thymidylate
CC       synthase family. {ECO:0000256|ARBA:ARBA00006900,
CC       ECO:0000256|PIRNR:PIRNR000389}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the dihydrofolate
CC       reductase family. {ECO:0000256|ARBA:ARBA00010176,
CC       ECO:0000256|PIRNR:PIRNR000389}.
CC   -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ
CC       whole genome shotgun (WGS) entry which is preliminary data.
CC       {ECO:0000313|EMBL:ESS34444.1}.
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DR   EMBL; AAYL02000077; ESS34444.1; -; Genomic_DNA.
DR   AlphaFoldDB; B9PR34; -.
DR   SMR; B9PR34; -.
DR   STRING; 432359.B9PR34; -.
DR   PaxDb; 432359-B9PR34; -.
DR   VEuPathDB; ToxoDB:TGVEG_249180; -.
DR   eggNOG; KOG0673; Eukaryota.
DR   eggNOG; KOG1324; Eukaryota.
DR   OMA; ILCAWNV; -.
DR   OrthoDB; 959at5809; -.
DR   UniPathway; UPA00077; UER00158.
DR   Proteomes; UP000002226; Unassembled WGS sequence.
DR   GO; GO:0005829; C:cytosol; IEA:TreeGrafter.
DR   GO; GO:0005739; C:mitochondrion; IEA:TreeGrafter.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004799; F:thymidylate synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006231; P:dTMP biosynthetic process; IEA:InterPro.
DR   GO; GO:0006730; P:one-carbon metabolic process; IEA:InterPro.
DR   GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR   CDD; cd00209; DHFR; 1.
DR   CDD; cd00351; TS_Pyrimidine_HMase; 1.
DR   FunFam; 3.30.572.10:FF:000002; Possible thymidylate synthase; 1.
DR   Gene3D; 3.40.430.10; Dihydrofolate Reductase, subunit A; 1.
DR   Gene3D; 3.30.572.10; Thymidylate synthase/dCMP hydroxymethylase domain; 1.
DR   HAMAP; MF_00008; Thymidy_synth_bact; 1.
DR   InterPro; IPR024072; DHFR-like_dom_sf.
DR   InterPro; IPR012262; DHFR-TS.
DR   InterPro; IPR017925; DHFR_CS.
DR   InterPro; IPR001796; DHFR_dom.
DR   InterPro; IPR045097; Thymidate_synth/dCMP_Mease.
DR   InterPro; IPR023451; Thymidate_synth/dCMP_Mease_dom.
DR   InterPro; IPR036926; Thymidate_synth/dCMP_Mease_sf.
DR   InterPro; IPR000398; Thymidylate_synthase.
DR   InterPro; IPR020940; Thymidylate_synthase_AS.
DR   NCBIfam; NF002497; PRK01827.1-3; 1.
DR   NCBIfam; TIGR03284; thym_sym; 1.
DR   PANTHER; PTHR11548:SF2; THYMIDYLATE SYNTHASE; 1.
DR   PANTHER; PTHR11548; THYMIDYLATE SYNTHASE 1; 1.
DR   Pfam; PF00186; DHFR_1; 1.
DR   Pfam; PF00303; Thymidylat_synt; 1.
DR   PIRSF; PIRSF000389; DHFR-TS; 1.
DR   PRINTS; PR00108; THYMDSNTHASE.
DR   SUPFAM; SSF53597; Dihydrofolate reductase-like; 1.
DR   SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 1.
DR   PROSITE; PS00075; DHFR_1; 1.
DR   PROSITE; PS51330; DHFR_2; 1.
DR   PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE   3: Inferred from homology;
KW   Methyltransferase {ECO:0000256|ARBA:ARBA00022603,
KW   ECO:0000256|PIRNR:PIRNR000389};
KW   Multifunctional enzyme {ECO:0000256|ARBA:ARBA00023268};
KW   NADP {ECO:0000256|ARBA:ARBA00022857, ECO:0000256|PROSITE-ProRule:PRU00660};
KW   Nucleotide biosynthesis {ECO:0000256|ARBA:ARBA00022727,
KW   ECO:0000256|PIRNR:PIRNR000389};
KW   One-carbon metabolism {ECO:0000256|ARBA:ARBA00022563,
KW   ECO:0000256|PIRNR:PIRNR000389};
KW   Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW   ECO:0000256|PIRNR:PIRNR000389};
KW   Reference proteome {ECO:0000313|Proteomes:UP000002226};
KW   Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000389}.
FT   DOMAIN          4..250
FT                   /note="DHFR"
FT                   /evidence="ECO:0000259|PROSITE:PS51330"
FT   REGION          256..282
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        261..275
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        489
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000389-1,
FT                   ECO:0000256|PROSITE-ProRule:PRU10016"
SQ   SEQUENCE   610 AA;  68752 MW;  CFAF564416D04A29 CRC64;
     MQKPVCLVVA MTPKRGIGIN NGLPWPHLTT DFKHFSRVTK TTPEEASRLN GWLPRKFAKT
     GDSGLPSPSV GKRFNAVVMG RKTWESMPRK FRPLVDRLNI VVSSSLKEED IAAEKPQAEG
     QQRVRVCASL PAALSLLEEE YKDSVDQIFV VGGAGLYEAA LSLGVASHLY ITRVAREFPC
     DVFFPAFPGD DILSNKSTAA QAAAPAESVF VPFCPELGRE KDNEATYRPI FISKTFSDNG
     VPYDFVVLEK RRKTDDAATA EPSNAMSSLT STRETTPVHG LQAPSSAAAI APVLAWMDEE
     DRKKREQKEL IRAVPHVHFR GHEEFQYLDL IADIINNGRT MDDRTGVGVI SKFGCTMRYS
     LDQAFPLLTT KRVFWKGVLE ELLWFIRGDT NANHLSEKGV KIWDKNVTRE FLDSRNLPHR
     EVGDIGPGYG FQWRHFGAAY KDMHTDYTGQ GVDQLKNVIQ MLRTNPTDRR MLMTAWNPAA
     LDEMALPPCH LLCQFYVNDQ KELSCIMYQR SCDVGLGVPF NIASYSLLTL MVAHVCNLKP
     KEFIHFMGNT HVYTNHVEAL KEQLRREPRP FPIVNILNKE RIKEIDDFTA EDFEVVGYVP
     HGRIQMEMAV
//