DRTS_PLACH
ID DRTS_PLACH Reviewed; 583 AA.
AC P20712; Q27715;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 112.
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;
OS Plasmodium chabaudi.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Vinckeia).
OX NCBI_TaxID=5825;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2601715; DOI=10.1128/mcb.9.11.5182-5188.1989;
RA Cowman A.F., Lew A.M.;
RT "Antifolate drug selection results in duplication and rearrangement of
RT chromosome 7 in Plasmodium chabaudi.";
RL Mol. Cell. Biol. 9:5182-5188(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-193.
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 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 -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP = 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; M30834; AAA29587.1; -; Genomic_DNA.
DR EMBL; L28120; AAB59201.1; -; Genomic_DNA.
DR PIR; A33484; RDZQTB.
DR AlphaFoldDB; P20712; -.
DR SMR; P20712; -.
DR PRIDE; P20712; -.
DR VEuPathDB; PlasmoDB:PCHAS_0728300; -.
DR eggNOG; KOG0673; Eukaryota.
DR eggNOG; KOG1324; Eukaryota.
DR UniPathway; UPA00077; UER00158.
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:0032259; P:methylation; IEA:UniProtKB-KW.
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 CDD; cd00351; TS_Pyrimidine_HMase; 1.
DR Gene3D; 3.30.572.10; -; 1.
DR Gene3D; 3.40.430.10; -; 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 PANTHER; PTHR11548; PTHR11548; 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; SSF53597; 1.
DR SUPFAM; SSF55831; SSF55831; 1.
DR TIGRFAMs; TIGR03284; thym_sym; 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; Multifunctional enzyme; NADP; Nucleotide biosynthesis;
KW One-carbon metabolism; Oxidoreductase; Transferase.
FT CHAIN 1..583
FT /note="Bifunctional dihydrofolate reductase-thymidylate
FT synthase"
FT /id="PRO_0000186348"
FT DOMAIN 9..229
FT /note="DHFR"
FT REGION 298..583
FT /note="Thymidylate synthase"
FT ACT_SITE 465
FT /evidence="ECO:0000250"
FT BINDING 36..42
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 51
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 104..106
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 125..128
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 165
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 166..173
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 171
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 186
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 320
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 466
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 484..488
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 496
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 526..528
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT VARIANT 106
FT /note="S -> I (in pyrimethamine resistance)"
FT CONFLICT 27
FT /note="G -> S (in Ref. 2; AAB59201)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="C -> S (in Ref. 2; AAB59201)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="I -> V (in Ref. 2; AAB59201)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 583 AA; 68051 MW; 4AA55E1C987E6FD7 CRC64;
MEDISEIFDI YAICACCKVL NSNEKAGCFS NKTFKGLGNE GGLPWKCNSV DMKHFSSVTS
YVNETNYMRL KWKRDRYMEK NNVKLNTDGI PSVDKLQNIV VMGKASWESI PSKFKPLQNR
INIILSRTLK KEDLAKEYNN VIIINSVDDL FPILKCIKYY KCFIIGGASV YKEFLDRNLI
KKIYFTRINN AYTCDVLFPD INEDLFKITS ISDVYSSNNT TLDFVIYSKT KEIHEEINPN
DELFNNTFLG VCDEKNTNFD DEDDYTYFSF NKHKDNIKKN SEHAHHFKIY NSIKYKHHPE
YQYLNIIYDI IMHGNKQDDR TGVGVLSKFG YMMKFNLSEY FPLLTTKKLF VRGIIEELLW
FIRGETNGNT LLEKNVRIWE ANGTREFLDN RKLFHREVND LGPIYGFQWR HFGAEYTDMH
ADYKDKGVDQ LKNIINLIKN DPTCRRIILC AWNVKDLDQM ALPPCHILCQ FYVFDGKLSC
IMYQRSCDLG LGVPFNIASY SIFTYMIAQV CNLQPAEFIH VLGNAHVYNN HVESLKVQLN
RTPYPFPTLK LNPEIKNIED FTISDFTVQN YVHHDKISMD MAA
