ID DRTS_ORYSJ Reviewed; 494 AA.
AC Q2QRX6;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 2.
DT 24-JAN-2024, entry version 101.
DE RecName: Full=Putative 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;
GN OrderedLocusNames=Os12g0446900, LOC_Os12g26060;
OS Oryza sativa subsp. japonica (Rice).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; Liliopsida; Poales; Poaceae; BOP clade;
OC Oryzoideae; Oryzeae; Oryzinae; Oryza; Oryza sativa.
OX NCBI_TaxID=39947;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Nipponbare;
RX PubMed=16188032; DOI=10.1186/1741-7007-3-20;
RG The rice chromosomes 11 and 12 sequencing consortia;
RT "The sequence of rice chromosomes 11 and 12, rich in disease resistance
RT genes and recent gene duplications.";
RL BMC Biol. 3:20-20(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Nipponbare;
RX PubMed=16100779; DOI=10.1038/nature03895;
RG International rice genome sequencing project (IRGSP);
RT "The map-based sequence of the rice genome.";
RL Nature 436:793-800(2005).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=cv. Nipponbare;
RX PubMed=18089549; DOI=10.1093/nar/gkm978;
RG The rice annotation project (RAP);
RT "The rice annotation project database (RAP-DB): 2008 update.";
RL Nucleic Acids Res. 36:D1028-D1033(2008).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=cv. Nipponbare;
RX PubMed=24280374; DOI=10.1186/1939-8433-6-4;
RA Kawahara Y., de la Bastide M., Hamilton J.P., Kanamori H., McCombie W.R.,
RA Ouyang S., Schwartz D.C., Tanaka T., Wu J., Zhou S., Childs K.L.,
RA Davidson R.M., Lin H., Quesada-Ocampo L., Vaillancourt B., Sakai H.,
RA Lee S.S., Kim J., Numa H., Itoh T., Buell C.R., Matsumoto T.;
RT "Improvement of the Oryza sativa Nipponbare reference genome using next
RT generation sequence and optical map data.";
RL Rice 6:4-4(2013).
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 (By similarity). {ECO:0000250}.
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 -!- 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; DP000011; ABA98037.2; -; Genomic_DNA.
DR EMBL; AP008218; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP014968; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; Q2QRX6; -.
DR SMR; Q2QRX6; -.
DR STRING; 39947.Q2QRX6; -.
DR PaxDb; 39947-Q2QRX6; -.
DR eggNOG; KOG0673; Eukaryota.
DR eggNOG; KOG1324; Eukaryota.
DR InParanoid; Q2QRX6; -.
DR PlantReactome; R-OSA-1119265; Tetrahydrofolate biosynthesis I.
DR PlantReactome; R-OSA-1119523; Tetrahydrofolate biosynthesis II.
DR UniPathway; UPA00077; UER00158.
DR Proteomes; UP000000763; Chromosome 12.
DR Proteomes; UP000059680; Chromosome 12.
DR Genevisible; Q2QRX6; OS.
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; IBA:GO_Central.
DR GO; GO:0004799; F:thymidylate synthase activity; IBA:GO_Central.
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 GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00209; DHFR; 1.
DR CDD; cd00351; TS_Pyrimidine_HMase; 1.
DR Gene3D; 3.40.430.10; Dihydrofolate Reductase, subunit A; 1.
DR Gene3D; 3.30.572.10; Thymidylate synthase/dCMP hydroxymethylase domain; 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 NCBIfam; TIGR03284; thym_sym; 1.
DR PANTHER; PTHR11548:SF15; BIFUNCTIONAL DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE-RELATED; 1.
DR PANTHER; PTHR11548; THYMIDYLATE SYNTHASE 1; 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; Dihydrofolate reductase-like; 1.
DR SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 1.
DR PROSITE; PS00075; DHFR_1; 1.
DR PROSITE; PS51330; DHFR_2; 1.
DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE 3: Inferred from homology;
KW Methyltransferase; Multifunctional enzyme; NADP; Nucleotide biosynthesis;
KW One-carbon metabolism; Oxidoreductase; Reference proteome; Transferase.
FT CHAIN 1..494
FT /note="Putative bifunctional dihydrofolate reductase-
FT thymidylate synthase"
FT /id="PRO_0000247485"
FT DOMAIN 1..167
FT /note="DHFR"
FT REGION 170..494
FT /note="Thymidylate synthase"
FT ACT_SITE 376
FT /evidence="ECO:0000250"
FT BINDING 2..8
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 16
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 40..42
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 61..64
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 103
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 104..111
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 124
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 231
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 377
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 395..399
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 407
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 437..439
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
SQ SEQUENCE 494 AA; 55977 MW; 1F7F2D5162109A1B CRC64;
MGIGKDGTLP WKLPGDLKFF KDITVTTSDP SKKNAVVMGR KTWESIPLKF RPLPGRLNVI
LTRSGSFDFA TAENVVICGS LDSALQLLAT TPYCLTVEKT FIIGGGEILR QSLNAPACEA
IHLTDIESSI ECDTFIPPID LSMFHPWYSS FPVVENGIKH SFISFVRVTK SIAEANDSSG
KELTGNDSKK VKFEIENFSF LPKMIFERHE EYQYLNLVQD IIRNGAKKND RTGTGTVSKF
GCQMRFNLRR NFPLLTTKRV FWRGVLEELL WFISGSTNAK VLQEKGIHIW DGNASRQYLD
SIGLTQREEG DLGPVYGFQW RHFGAEYTDM HADYVGKGFD QLMDVIDKIK NNPDDRRIIL
SAWNPTDLKK MALPPCHMFA QFYVENGELS CQMYQRSADM GLGVPFNIAS YSLLTCMIAQ
VCDLSPGDFV HVIGDAHVYR THVEALEEQM RKQPKPFPIL KINPVKKDID SFVTSDFKLV
RYDPHHKIEM KMAV
//
