ID   DRTS1_ARATH             Reviewed;         519 AA.
AC   Q05762; Q9SIW4;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   27-MAY-2002, sequence version 2.
DT   16-JUN-2009, entry version 77.
DE   RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase 1;
DE            Short=DHFR-TS 1;
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;
GN   Name=THY-1; OrderedLocusNames=At2g16370; ORFNames=F16F14.13;
OS   Arabidopsis thaliana (Mouse-ear cress).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliophyta; eudicotyledons; core eudicotyledons;
OC   rosids; eurosids II; Brassicales; Brassicaceae; Arabidopsis.
OX   NCBI_TaxID=3702;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=cv. Landsberg erecta;
RX   MEDLINE=93386189; PubMed=8374616;
RA   Lazar G., Zhang H., Goodman H.M.;
RT   "The origin of the bifunctional dihydrofolate reductase-thymidylate
RT   synthase isogenes of Arabidopsis thaliana.";
RL   Plant J. 3:657-668(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=cv. Columbia;
RX   MEDLINE=20083487; PubMed=10617197; DOI=10.1038/45471;
RA   Lin X., Kaul S., Rounsley S.D., Shea T.P., Benito M.-I., Town C.D.,
RA   Fujii C.Y., Mason T.M., Bowman C.L., Barnstead M.E., Feldblyum T.V.,
RA   Buell C.R., Ketchum K.A., Lee J.J., Ronning C.M., Koo H.L.,
RA   Moffat K.S., Cronin L.A., Shen M., Pai G., Van Aken S., Umayam L.,
RA   Tallon L.J., Gill J.E., Adams M.D., Carrera A.J., Creasy T.H.,
RA   Goodman H.M., Somerville C.R., Copenhaver G.P., Preuss D.,
RA   Nierman W.C., White O., Eisen J.A., Salzberg S.L., Fraser C.M.,
RA   Venter J.C.;
RT   "Sequence and analysis of chromosome 2 of the plant Arabidopsis
RT   thaliana.";
RL   Nature 402:761-768(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=cv. Columbia;
RX   MEDLINE=22954850; PubMed=14593172; DOI=10.1126/science.1088305;
RA   Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J.,
RA   Southwick A.M., Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F.,
RA   Karlin-Newmann G., Liu S.X., Lam B., Sakano H., Wu T., Yu G.,
RA   Miranda M., Quach H.L., Tripp M., Chang C.H., Lee J.M., Toriumi M.J.,
RA   Chan M.M., Tang C.C., Onodera C.S., Deng J.M., Akiyama K., Ansari Y.,
RA   Arakawa T., Banh J., Banno F., Bowser L., Brooks S.Y., Carninci P.,
RA   Chao Q., Choy N., Enju A., Goldsmith A.D., Gurjal M., Hansen N.F.,
RA   Hayashizaki Y., Johnson-Hopson C., Hsuan V.W., Iida K., Karnes M.,
RA   Khan S., Koesema E., Ishida J., Jiang P.X., Jones T., Kawai J.,
RA   Kamiya A., Meyers C., Nakajima M., Narusaka M., Seki M., Sakurai T.,
RA   Satou M., Tamse R., Vaysberg M., Wallender E.K., Wong C., Yamamura Y.,
RA   Yuan S., Shinozaki K., Davis R.W., Theologis A., Ecker J.R.;
RT   "Empirical analysis of transcriptional activity in the Arabidopsis
RT   genome.";
RL   Science 302:842-846(2003).
CC   -!- FUNCTION: TS is exclusively involved in de novo dTMP biosynthesis.
CC       DHFR can have two different roles depending on the source of
CC       dihydrofolate: de novo synthesis of tetrahydrofolate or recycling
CC       of the dihydrofolate released as one of the end products of the TS
CC       catalyzed reaction.
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   -!- SUBUNIT: Heterodimer or homodimer (By similarity).
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; L08593; AAA32788.1; -; mRNA.
DR   EMBL; AC007047; AAD22302.1; -; Genomic_DNA.
DR   EMBL; AY063968; AAL36324.1; -; mRNA.
DR   EMBL; AY114032; AAM45080.1; -; mRNA.
DR   IPI; IPI00530946; -.
DR   PIR; E84539; E84539.
DR   RefSeq; NP_179230.1; -.
DR   UniGene; At.27124; -.
DR   HSSP; P04818; 1HW4.
DR   PRIDE; Q05762; -.
DR   GeneID; 816134; -.
DR   GenomeReviews; CT485783_GR; AT2G16370.
DR   KEGG; ath:AT2G16370; -.
DR   NMPDR; fig|3702.1.peg.8626; -.
DR   TAIR; At2g16370; -.
DR   OMA; Q05762; HADYTGK.
DR   BRENDA; 1.5.1.3; 302.
DR   BRENDA; 2.1.1.45; 302.
DR   ArrayExpress; Q05762; -.
DR   GermOnline; AT2G16370; Arabidopsis thaliana.
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   2: Evidence at transcript level;
KW   Complete proteome; Methyltransferase; Multifunctional enzyme; NADP;
KW   Nucleotide biosynthesis; One-carbon metabolism; Oxidoreductase;
KW   Transferase.
FT   CHAIN         1    519       Bifunctional dihydrofolate reductase-
FT                                thymidylate synthase 1.
FT                                /FTId=PRO_0000186355.
FT   DOMAIN       21    198       DHFR.
FT   REGION      201    234       Hinge.
FT   REGION      235    519       Thymidylate synthase.
FT   ACT_SITE    401    401       By similarity.
FT   CONFLICT    120    120       A -> R (in Ref. 1; AAA32788).
FT   CONFLICT    478    478       L -> P (in Ref. 1; AAA32788).
FT   CONFLICT    485    485       M -> L (in Ref. 1; AAA32788).
SQ   SEQUENCE   519 AA;  58143 MW;  B5EB36A3A936580F CRC64;
     MATTTLNDSV TTTLASEPQR TYQVVVAATK EMGIGKDGKL PWNLPTDLKF FKDITLTTSD
     SSKKNAVVMG RKTWESIPIK YRPLSGRLNV VLTRSGGFDI ANTENVVTCS SVDSALDLLA
     APPYCLSIER VFVIGGGDIL REALNRPSCD AIHLTEIDTS VDCDTFIPAI DTSVYQPWSS
     SFPVTENGLR FCFTTFVRVK SSADESSDES NGSQSLQFDG KKFLFLPKMV FDQHEEFLYL
     NMVEDIISNG NVKNDRTGTG TLSKFGCQMK FNLRRSFPLL TTKRVFWRGV VEELLWFISG
     STNAKVLQEK GIHIWDGNAS REYLDGIGLT EREEGDLGPV YGFQWRHFGA KYTDMHADYT
     GQGFDQLVDV IDKIKNNPDD RRIIMSAWNP SDLKLMALPP CHMFAQFYVA EGELSCQMYQ
     RSADMGLGVP FNIASYSLLT CMLAHVCDLV PGDFIHVLGD AHVYKTHVRP LQEQLLNLPK
     PFPVMKINPE KKQIDSFVAS DFDLTGYDPH KKIEMKMAV
//