DRTS1_ARATH
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 03-AUG-2022, entry version 164.
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; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX NCBI_TaxID=3702;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=cv. Landsberg erecta;
RX PubMed=8374616; DOI=10.1111/j.1365-313x.1993.00657.x;
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 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., Moffat K.S.,
RA Cronin L.A., Shen M., Pai G., Van Aken S., Umayam L., Tallon L.J.,
RA Gill J.E., Adams M.D., Carrera A.J., Creasy T.H., Goodman H.M.,
RA Somerville C.R., Copenhaver G.P., Preuss D., Nierman W.C., White O.,
RA Eisen J.A., Salzberg S.L., Fraser C.M., Venter J.C.;
RT "Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana.";
RL Nature 402:761-768(1999).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=cv. Columbia;
RX PubMed=27862469; DOI=10.1111/tpj.13415;
RA Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA Town C.D.;
RT "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT genome.";
RL Plant J. 89:789-804(2017).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. Columbia;
RX PubMed=14593172; DOI=10.1126/science.1088305;
RA Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA Ecker J.R.;
RT "Empirical analysis of transcriptional activity in the Arabidopsis
RT genome.";
RL Science 302:842-846(2003).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
CC -!- FUNCTION: Bifunctional enzyme. Involved in de novo dTMP biosynthesis.
CC Key enzyme in folate metabolism. Can play two different roles depending
CC on the source of dihydrofolate: de novo synthesis of tetrahydrofolate
CC or recycling of the dihydrofolate released as one of the end products
CC of the TS catalyzed reaction. Catalyzes an essential reaction for de
CC novo glycine and purine synthesis, DNA precursor synthesis, and for the
CC conversion of dUMP to dTMP.
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: Heterodimer or homodimer. {ECO:0000250}.
CC -!- INTERACTION:
CC Q05762; Q9LV27: LST8-1; NbExp=6; IntAct=EBI-4455031, EBI-4453099;
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; L08593; AAA32788.1; -; mRNA.
DR EMBL; AC007047; AAD22302.1; -; Genomic_DNA.
DR EMBL; CP002685; AEC06489.1; -; Genomic_DNA.
DR EMBL; CP002685; ANM62435.1; -; Genomic_DNA.
DR EMBL; AY063968; AAL36324.1; -; mRNA.
DR EMBL; AY114032; AAM45080.1; -; mRNA.
DR PIR; E84539; E84539.
DR RefSeq; NP_001324593.1; NM_001335473.1.
DR RefSeq; NP_179230.1; NM_127191.4.
DR AlphaFoldDB; Q05762; -.
DR SMR; Q05762; -.
DR BioGRID; 1492; 3.
DR IntAct; Q05762; 2.
DR STRING; 3702.AT2G16370.1; -.
DR iPTMnet; Q05762; -.
DR MetOSite; Q05762; -.
DR PaxDb; Q05762; -.
DR PRIDE; Q05762; -.
DR ProteomicsDB; 224371; -.
DR EnsemblPlants; AT2G16370.1; AT2G16370.1; AT2G16370.
DR EnsemblPlants; AT2G16370.3; AT2G16370.3; AT2G16370.
DR GeneID; 816134; -.
DR Gramene; AT2G16370.1; AT2G16370.1; AT2G16370.
DR Gramene; AT2G16370.3; AT2G16370.3; AT2G16370.
DR KEGG; ath:AT2G16370; -.
DR Araport; AT2G16370; -.
DR TAIR; locus:2042649; AT2G16370.
DR eggNOG; KOG0673; Eukaryota.
DR eggNOG; KOG1324; Eukaryota.
DR HOGENOM; CLU_021669_2_2_1; -.
DR InParanoid; Q05762; -.
DR OrthoDB; 1197342at2759; -.
DR PhylomeDB; Q05762; -.
DR BioCyc; ARA:AT2G16370-MON; -.
DR UniPathway; UPA00077; UER00158.
DR PRO; PR:Q05762; -.
DR Proteomes; UP000006548; Chromosome 2.
DR ExpressionAtlas; Q05762; baseline and differential.
DR Genevisible; Q05762; AT.
DR GO; GO:0005737; C:cytoplasm; IDA:TAIR.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0004146; F:dihydrofolate reductase activity; IDA:TAIR.
DR GO; GO:0004799; F:thymidylate synthase activity; ISS:TAIR.
DR GO; GO:0009257; P:10-formyltetrahydrofolate biosynthetic process; ISS:TAIR.
DR GO; GO:0006231; P:dTMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
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 1: Evidence at protein level;
KW Acetylation; Methyltransferase; Multifunctional enzyme; NADP;
KW Nucleotide biosynthesis; One-carbon metabolism; Oxidoreductase;
KW Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..519
FT /note="Bifunctional dihydrofolate reductase-thymidylate
FT synthase 1"
FT /id="PRO_0000186355"
FT DOMAIN 21..198
FT /note="DHFR"
FT REGION 201..234
FT /note="Hinge"
FT REGION 235..519
FT /note="Thymidylate synthase"
FT ACT_SITE 401
FT /evidence="ECO:0000250"
FT BINDING 25
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 27
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 33..39
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 47
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 71..73
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 92..95
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 134
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 135..142
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 155
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 256
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 402
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 420..424
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 432
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 462..464
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CONFLICT 120
FT /note="A -> R (in Ref. 1; AAA32788)"
FT /evidence="ECO:0000305"
FT CONFLICT 478
FT /note="L -> P (in Ref. 1; AAA32788)"
FT /evidence="ECO:0000305"
FT CONFLICT 485
FT /note="M -> L (in Ref. 1; AAA32788)"
FT /evidence="ECO:0000305"
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
