DRTS2_ARATH
ID DRTS2_ARATH Reviewed; 565 AA.
AC Q05763; Q0WT35;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase 2;
DE Short=DHFR-TS 2;
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-2; OrderedLocusNames=At4g34570; ORFNames=T4L20.150;
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=10617198; DOI=10.1038/47134;
RA Mayer K.F.X., Schueller C., Wambutt R., Murphy G., Volckaert G., Pohl T.,
RA Duesterhoeft A., Stiekema W., Entian K.-D., Terryn N., Harris B.,
RA Ansorge W., Brandt P., Grivell L.A., Rieger M., Weichselgartner M.,
RA de Simone V., Obermaier B., Mache R., Mueller M., Kreis M., Delseny M.,
RA Puigdomenech P., Watson M., Schmidtheini T., Reichert B., Portetelle D.,
RA Perez-Alonso M., Boutry M., Bancroft I., Vos P., Hoheisel J.,
RA Zimmermann W., Wedler H., Ridley P., Langham S.-A., McCullagh B.,
RA Bilham L., Robben J., van der Schueren J., Grymonprez B., Chuang Y.-J.,
RA Vandenbussche F., Braeken M., Weltjens I., Voet M., Bastiaens I., Aert R.,
RA Defoor E., Weitzenegger T., Bothe G., Ramsperger U., Hilbert H., Braun M.,
RA Holzer E., Brandt A., Peters S., van Staveren M., Dirkse W., Mooijman P.,
RA Klein Lankhorst R., Rose M., Hauf J., Koetter P., Berneiser S., Hempel S.,
RA Feldpausch M., Lamberth S., Van den Daele H., De Keyser A., Buysshaert C.,
RA Gielen J., Villarroel R., De Clercq R., van Montagu M., Rogers J.,
RA Cronin A., Quail M.A., Bray-Allen S., Clark L., Doggett J., Hall S.,
RA Kay M., Lennard N., McLay K., Mayes R., Pettett A., Rajandream M.A.,
RA Lyne M., Benes V., Rechmann S., Borkova D., Bloecker H., Scharfe M.,
RA Grimm M., Loehnert T.-H., Dose S., de Haan M., Maarse A.C., Schaefer M.,
RA Mueller-Auer S., Gabel C., Fuchs M., Fartmann B., Granderath K., Dauner D.,
RA Herzl A., Neumann S., Argiriou A., Vitale D., Liguori R., Piravandi E.,
RA Massenet O., Quigley F., Clabauld G., Muendlein A., Felber R., Schnabl S.,
RA Hiller R., Schmidt W., Lecharny A., Aubourg S., Chefdor F., Cooke R.,
RA Berger C., Monfort A., Casacuberta E., Gibbons T., Weber N., Vandenbol M.,
RA Bargues M., Terol J., Torres A., Perez-Perez A., Purnelle B., Bent E.,
RA Johnson S., Tacon D., Jesse T., Heijnen L., Schwarz S., Scholler P.,
RA Heber S., Francs P., Bielke C., Frishman D., Haase D., Lemcke K.,
RA Mewes H.-W., Stocker S., Zaccaria P., Bevan M., Wilson R.K.,
RA de la Bastide M., Habermann K., Parnell L., Dedhia N., Gnoj L., Schutz K.,
RA Huang E., Spiegel L., Sekhon M., Murray J., Sheet P., Cordes M.,
RA Abu-Threideh J., Stoneking T., Kalicki J., Graves T., Harmon G.,
RA Edwards J., Latreille P., Courtney L., Cloud J., Abbott A., Scott K.,
RA Johnson D., Minx P., Bentley D., Fulton B., Miller N., Greco T., Kemp K.,
RA Kramer J., Fulton L., Mardis E., Dante M., Pepin K., Hillier L.W.,
RA Nelson J., Spieth J., Ryan E., Andrews S., Geisel C., Layman D., Du H.,
RA Ali J., Berghoff A., Jones K., Drone K., Cotton M., Joshu C., Antonoiu B.,
RA Zidanic M., Strong C., Sun H., Lamar B., Yordan C., Ma P., Zhong J.,
RA Preston R., Vil D., Shekher M., Matero A., Shah R., Swaby I.K.,
RA O'Shaughnessy A., Rodriguez M., Hoffman J., Till S., Granat S., Shohdy N.,
RA Hasegawa A., Hameed A., Lodhi M., Johnson A., Chen E., Marra M.A.,
RA Martienssen R., McCombie W.R.;
RT "Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.";
RL Nature 402:769-777(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;
RA Totoki Y., Seki M., Ishida J., Nakajima M., Enju A., Kamiya A.,
RA Narusaka M., Shin-i T., Nakagawa M., Sakamoto N., Oishi K., Kohara Y.,
RA Kobayashi M., Toyoda A., Sakaki Y., Sakurai T., Iida K., Akiyama K.,
RA Satou M., Toyoda T., Konagaya A., Carninci P., Kawai J., Hayashizaki Y.,
RA Shinozaki K.;
RT "Large-scale analysis of RIKEN Arabidopsis full-length (RAFL) cDNAs.";
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 48-565.
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).
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 -!- 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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA32789.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAA18836.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAB80174.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; L08594; AAA32789.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL023094; CAA18836.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL161585; CAB80174.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CP002687; AEE86394.1; -; Genomic_DNA.
DR EMBL; AK227728; BAE99713.1; -; mRNA.
DR EMBL; BT003159; AAO24591.1; -; mRNA.
DR PIR; T05277; T05277.
DR RefSeq; NP_001328948.1; NM_001342290.1.
DR RefSeq; NP_001328950.1; NM_001342292.1.
DR RefSeq; NP_195183.2; NM_119623.5.
DR AlphaFoldDB; Q05763; -.
DR SMR; Q05763; -.
DR BioGRID; 14891; 1.
DR IntAct; Q05763; 1.
DR STRING; 3702.AT4G34570.1; -.
DR PaxDb; Q05763; -.
DR PRIDE; Q05763; -.
DR ProteomicsDB; 224372; -.
DR EnsemblPlants; AT4G34570.1; AT4G34570.1; AT4G34570.
DR GeneID; 829609; -.
DR Gramene; AT4G34570.1; AT4G34570.1; AT4G34570.
DR KEGG; ath:AT4G34570; -.
DR Araport; AT4G34570; -.
DR TAIR; locus:2139544; AT4G34570.
DR eggNOG; KOG0673; Eukaryota.
DR eggNOG; KOG1324; Eukaryota.
DR HOGENOM; CLU_021669_2_2_1; -.
DR InParanoid; Q05763; -.
DR OrthoDB; 1197342at2759; -.
DR PhylomeDB; Q05763; -.
DR BioCyc; ARA:AT4G34570-MON; -.
DR UniPathway; UPA00077; UER00158.
DR PRO; PR:Q05763; -.
DR Proteomes; UP000006548; Chromosome 4.
DR ExpressionAtlas; Q05763; baseline and differential.
DR Genevisible; Q05763; AT.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:TAIR.
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 2: Evidence at transcript level;
KW Methyltransferase; Multifunctional enzyme; NADP; Nucleotide biosynthesis;
KW One-carbon metabolism; Oxidoreductase; Reference proteome; Transferase.
FT CHAIN 1..565
FT /note="Bifunctional dihydrofolate reductase-thymidylate
FT synthase 2"
FT /id="PRO_0000186356"
FT DOMAIN 65..242
FT /note="DHFR"
FT REGION 245..280
FT /note="Hinge"
FT REGION 281..565
FT /note="Thymidylate synthase"
FT ACT_SITE 447
FT /evidence="ECO:0000250"
FT BINDING 69
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 71
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 77..83
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 91
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 115..117
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 136..139
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 178
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 179..186
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 199
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 302
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 448
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 466..470
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 478
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 508..510
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
SQ SEQUENCE 565 AA; 63209 MW; C442A1402A591DD9 CRC64;
MRCLQNSAKT LPLAFKSALL PLSQRWFCKF SPKPSSLTNI FKVSISTMAN TLNGNVIMTS
KPQSTYQVVV AATKEMGIGK DGKLPWNLPT DLKFFKDLTL STSDSAKKNA VVMGRKTWES
IPKKYRPLSG RLNVVLSRSS GFDIANTENV VTCSSIDSAL DLLAAPPFSL SIEKVFVIGG
GDILREALNK PSCEAIHITE IDTSIDCDTF IPTVDTSAYQ PWCSSFPICE NGLRFSFTTH
VRVKSSSAGE ASDESDGSKV LQVDWKKFSS VLPKMIFDRH EEYLYLNLVK EIISNGNLKD
DRTGTGTLSK FGCQMKFNLR RNFPLLTTKR VFWRGVVEEL LWFISGSTNA KVLQEKGIRI
WDGNASRAYL DGIGLTEREE GDLGPVYGFQ WRHFGAKYTD MHADYTGQGF DQLLDVINKI
KNNPDDRRII MSAWNPSDLK LMALPPCHMF AQFYVANGEL SCQMYQRSAD MGLGVPFNIA
SYSLLTCILA HVCDLVPGDF IHVIGDAHVY KNHVRPLQEQ LENPPKPFPV LKINPEKKDI
DSFVADDFEL IGYDPHKKID MKMAV
