ID   DRTS_CRIFA              Reviewed;         515 AA.
AC   Q23695;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   16-JUN-2009, entry version 47.
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   Crithidia fasciculata.
OC   Eukaryota; Euglenozoa; Kinetoplastida; Trypanosomatidae; Crithidia.
OX   NCBI_TaxID=5656;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=89219166; PubMed=2540436; DOI=10.1016/0166-6851(89)90007-8;
RA   Hughes D.E., Shonekan O.A., Simpson L.;
RT   "Structure, genomic organization and transcription of the bifunctional
RT   dihydrofolate reductase-thymidylate synthase gene from Crithidia
RT   fasciculata.";
RL   Mol. Biochem. Parasitol. 34:155-166(1989).
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; M22852; AAA30318.1; -; Genomic_DNA.
DR   HSSP; P04818; 1HW4.
DR   BRENDA; 1.5.1.3; 571.
DR   BRENDA; 2.1.1.45; 571.
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; FALSE_NEG.
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    515       Bifunctional dihydrofolate reductase-
FT                                thymidylate synthase.
FT                                /FTId=PRO_0000186343.
FT   DOMAIN       26    228       DHFR.
FT   REGION      233    515       Thymidylate synthase.
FT   ACT_SITE    385    385       By similarity.
SQ   SEQUENCE   515 AA;  58294 MW;  8327DAB231535921 CRC64;
     MSRAAAKFKI PMPVTKADFA FPSLRAFSIV VAADQQHGIG DGETIPWTVP ETLAFFKDQT
     TLLRNKKPPT EKKRNAVVMG RKTWEVPLKF RPLKGRLNVV LSCRRPVDDL LAQLPEEKRA
     AAAADVVING GLKEALHLLA RPPYCSSIET AYCIGGARVY TEAMQSPCVE KLKEVYLTRV
     HTAPTCNRFY EFVRRRRARA AVDLESTSGV KVSDAAAHLS YEIMKYVPHN AEERQYLELI
     DRIMKTGLVK EDRTGVGTIS LFGAQMFSLR DNQLPLLTTK RVFWRGVCEE LIWFLRGETN
     AHVLADKDIH IWDGNGSREF LDSRGLTENK EMDLGPVYGF QWRHFGADYK GFDANYDEGV
     DQIKTIVETL KTNDRRLLVT AWNPCALHKM AVRPCHLLGQ FYVNTQTKEL SCMLYQRCCD
     MGLGVPFNIA SYALLTILIA KATGLRPGEL VHTLGTAHVY SNHVEALKEQ LQRVPVAFPV
     LVFKKEREFL EDYESTDMEV VDYVPYPPIK MEMAV
//