ID   DRTS_LEIMA              Reviewed;         520 AA.
AC   P07382;
DT   01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1988, sequence version 1.
DT   25-NOV-2008, entry version 59.
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   Leishmania major.
OC   Eukaryota; Euglenozoa; Kinetoplastida; Trypanosomatidae; Leishmania.
OX   NCBI_TaxID=5664;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=86205996; PubMed=3458220;
RA   Beverley S.M., Ellenberger T.E., Cordingley J.S.;
RT   "Primary structure of the gene encoding the bifunctional dihydrofolate
RT   reductase-thymidylate synthase of Leishmania major.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:2584-2588(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=86287263; PubMed=3461439;
RA   Grumont R., Washtien W.L., Caput D., Santi D.V.;
RT   "Bifunctional thymidylate synthase-dihydrofolate reductase from
RT   Leishmania tropica: sequence homology with the corresponding
RT   monofunctional proteins.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:5387-5391(1986).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=LT25Z;
RA   Kapler G.M., Zhang K., Beverley S.;
RL   Submitted (FEB-1990) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   PARTIAL PROTEIN SEQUENCE OF 334-361.
RX   MEDLINE=86042631; PubMed=3903747;
RA   Garvey E.P., Santi D.V.;
RT   "Limited proteolysis of the bifunctional thymidylate synthase-
RT   dihydrofolate reductase from Leishmania tropica.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:7188-7192(1985).
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; M12734; AAA29232.1; -; Genomic_DNA.
DR   EMBL; M14330; AAA29272.1; -; Genomic_DNA.
DR   EMBL; X51733; CAA36019.1; -; Genomic_DNA.
DR   PIR; A23403; RDLNTS.
DR   HSSP; P04818; 1HW4.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; IEA:InterPro.
DR   GO; GO:0004799; F:thymidylate synthase activity; IEA:InterPro.
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:InterPro.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
DR   InterPro; IPR012262; DHFR-TS.
DR   InterPro; IPR001796; DHFR_reg.
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; PR00070; DHFR.
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   1: Evidence at protein level;
KW   Direct protein sequencing; Methyltransferase; Multifunctional enzyme;
KW   NADP; Nucleotide biosynthesis; One-carbon metabolism; Oxidoreductase;
KW   Transferase.
FT   CHAIN         1    520       Bifunctional dihydrofolate reductase-
FT                                thymidylate synthase.
FT                                /FTId=PRO_0000186345.
FT   DOMAIN       26    229       DHFR.
FT   REGION      234    520       Thymidylate synthase.
FT   ACT_SITE    400    400       By similarity.
FT   CONFLICT     28     28       S -> C (in Ref. 2; AAA29272).
FT   CONFLICT     49     49       V -> S (in Ref. 2; AAA29272).
FT   CONFLICT     72     76       KKRNA -> EEAQR (in Ref. 2; AAA29272).
FT   CONFLICT    125    127       QDV -> RML (in Ref. 2; AAA29272).
FT   CONFLICT    307    307       A -> T (in Ref. 2; AAA29272).
FT   CONFLICT    397    397       L -> V (in Ref. 2; AAA29272).
SQ   SEQUENCE   520 AA;  58689 MW;  7D221F2CF2BE43D4 CRC64;
     MSRAAARFKI PMPETKADFA FPSLRAFSIV VALDMQHGIG DGESIPWRVP EDMTFFKNQT
     TLLRNKKPPT EKKRNAVVMG RKTWESVPVK FRPLKGRLNI VLSSKATVEE LLAPLPEGQR
     AAAAQDVVVV NGGLAEALRL LARPLYCSSI ETAYCVGGAQ VYADAMLSPC IEKLQEVYLT
     RIYATAPACT RFFPFPPENA ATAWDLASSQ GRRKSEAEGL EFEICKYVPR NHEERQYLEL
     IDRIMKTGIV KEDRTGVGTI SLFGAQMRFS LRDNRLPLLT TKRVFWRGVC EELLWFLRGE
     TSAQLLADKD IHIWDGNGSR EFLDSRGLTE NKEMDLGPVY GFQWRHFGAD YKGFEANYDG
     EGVDQIKLIV ETIKTNPNDR RLLVTAWNPC ALQKMALPPC HLLAQFYVNT DTSELSCMLY
     QRSCDMGLGV PFNIASYALL TILIAKATGL RPGELVHTLG DAHVYRNHVD ALKAQLERVP
     HAFPTLIFKE ERQYLEDYEL TDMEVIDYVP HPAIKMEMAV
//