ID   DRTS_PLABA              Reviewed;         587 AA.
AC   Q27713; Q27714;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   16-JUN-2009, entry version 50.
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 berghei (strain Anka).
OC   Eukaryota; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC   Plasmodium; Plasmodium (Vinckeia).
OX   NCBI_TaxID=5823;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=95198769; PubMed=7891743; DOI=10.1016/0166-6851(94)00163-4;
RA   van Dijk M.R., McConkey G.A., Vinkenoog R., Waters A.P., Janse C.J.;
RT   "Mechanisms of pyrimethamine resistance in two different strains of
RT   Plasmodium berghei.";
RL   Mol. Biochem. Parasitol. 68:167-171(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-201.
RX   MEDLINE=95059225; PubMed=7969277; DOI=10.1016/0166-6851(94)90087-6;
RA   Cheng Q., Saul A.;
RT   "The dihydrofolate reductase domain of rodent malarias: point
RT   mutations and pyrimethamine resistance.";
RL   Mol. Biochem. Parasitol. 65:361-363(1994).
CC   -!- CATALYTIC ACTIVITY: 5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-
CC       dihydrofolate + NADPH.
CC   -!- CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + dUMP =
CC       dihydrofolate + dTMP.
CC   -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis;
CC       tetrahydrofolate from dihydrofolate: step 1/1.
CC   -!- MISCELLANEOUS: The reaction catalyzed by this enzyme represents an
CC       essential step for de novo glycine and purine synthesis, DNA
CC       precursor synthesis, and for the conversion of dUMP to dTMP.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the
CC       dihydrofolate reductase family.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the thymidylate
CC       synthase family.
CC   -!- SIMILARITY: Contains 1 DHFR (dihydrofolate reductase) domain.
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DR   EMBL; U12275; AAB60237.1; -; Genomic_DNA.
DR   EMBL; L28119; AAA29581.1; -; Genomic_DNA.
DR   HSSP; P13922; 1J3K.
DR   SMR; Q27713; 264-587.
DR   DrugBank; DB00440; Trimethoprim.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; IEA:EC.
DR   GO; GO:0004799; F:thymidylate synthase activity; IEA:EC.
DR   GO; GO:0006231; P:dTMP biosynthetic process; IEA:InterPro.
DR   GO; GO:0006545; P:glycine biosynthetic process; IEA:InterPro.
DR   GO; GO:0006730; P:one-carbon compound metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
DR   InterPro; IPR012262; DHFR-TS.
DR   InterPro; IPR001796; DHFR_reg.
DR   InterPro; IPR017925; Dihydrofolate_reductase_CS.
DR   InterPro; IPR000398; Thymidylat_synth_C.
DR   Gene3D; G3DSA:3.30.572.10; Thymidylat_synth_C; 1.
DR   PANTHER; PTHR11549:SF2; Thymidylat_synth_C; 1.
DR   Pfam; PF00186; DHFR_1; 1.
DR   Pfam; PF00303; Thymidylat_synt; 1.
DR   PIRSF; PIRSF000389; DHFR-TS; 1.
DR   PRINTS; PR00108; THYMDSNTHASE.
DR   ProDom; PD001180; Thymidylat_synth; 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;
KW   Nucleotide biosynthesis; One-carbon metabolism; Oxidoreductase;
KW   Transferase.
FT   CHAIN         1    587       Bifunctional dihydrofolate reductase-
FT                                thymidylate synthase.
FT                                /FTId=PRO_0000186347.
FT   DOMAIN        9    237       DHFR.
FT   REGION      301    587       Thymidylate synthase.
FT   ACT_SITE    469    469       By similarity.
FT   VARIANT     110    110       S -> N (in pyrimethamine resistance).
FT   VARIANT     177    177       S -> F (in pyrimethamine resistance).
SQ   SEQUENCE   587 AA;  68932 MW;  6E638C2B02FEC13A CRC64;
     MEDLSETFDI YAICACCKVL NDDEKVRCFN NKTFKGIGNA GVLPWKCNLI DMKYFSSVTS
     YINENNYIRL KWKRDKYMEK HNLKNNVELN TNIISSTNNL QNIVVMGKKS WESIPKKFKP
     LQNRINIILS RTLKKEDIVN ENNNENNNVI IIKSVDDLFP ILKCTKYYKC FIIGGSSVYK
     EFLDRNLIKK IYFTRINNSY NCDVLFPEIN ENLFKITSIS DVYYSNNTTL DFIIYSKTKE
     INPNEEVPNN TFLGVCDEQN KAFDDEDDYT YFSFNKNKEN IKKNSEHAHN FKIYNSIKYK
     NHPEYQYLNI IYDIIMHGNK QDDRTGVGVL SKFGYMMKFN LNEYFPLLTT KKLFIRGIIE
     ELLWFIRGET NGNTLLEKNV RIWEANGTRE FLDNRKLFHR EVNDLGPIYG FQWRHFGAEY
     TDMHDNYKDK GVDQLKNIIN LIKNDPTCRR IILCAWNVKN LDQMALPPCH ILCQFYVFDG
     KLSCIMYQRS CDLGLGVPFN IASYSIFTYM IAQVCNLQAA EFIHVLGNAH VYNNHIESLK
     IQLNRTPYPF PTLKLNPDIK NIEDFTISDF TVQNYVHHDK INMDMAA
//