DRTS_DAUCA
ID DRTS_DAUCA Reviewed; 528 AA.
AC P45350;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 99.
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 Daucus carota (Wild carrot).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; campanulids; Apiales; Apiaceae; Apioideae; Scandiceae; Daucinae;
OC Daucus; Daucus sect. Daucus.
OX NCBI_TaxID=4039;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=cv. Lunga di Amsterdam;
RX PubMed=8329682; DOI=10.1007/bf00015973;
RA Luo M., Piffanelli P., Rastelli L., Cella R.;
RT "Molecular cloning and analysis of a cDNA coding for the bifunctional
RT dihydrofolate reductase-thymidylate synthase of Daucus carota.";
RL Plant Mol. Biol. 22:427-435(1993).
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; Z17306; CAA78954.1; -; mRNA.
DR PIR; S35272; S35272.
DR AlphaFoldDB; P45350; -.
DR SMR; P45350; -.
DR UniPathway; UPA00077; UER00158.
DR GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0004799; F:thymidylate synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0006231; P:dTMP biosynthetic process; IEA:InterPro.
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; 3.30.572.10; -; 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; Transferase.
FT CHAIN 1..528
FT /note="Bifunctional dihydrofolate reductase-thymidylate
FT synthase"
FT /id="PRO_0000186357"
FT DOMAIN 23..200
FT /note="DHFR"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 202..528
FT /note="Thymidylate synthase"
FT ACT_SITE 409
FT /evidence="ECO:0000250"
FT BINDING 27
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 29
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 35..41
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 49
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 73..75
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 94..97
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 136
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 137..144
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 142
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 157
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 264
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 410
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 428..432
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 440
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 470..472
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
SQ SEQUENCE 528 AA; 59259 MW; 8BE07C221A546A56 CRC64;
MASELLANPT NGSGITRPDP QRTYQVVVAA TQNMGIGKDG KLPWRLPSDM KFFKDVTMTT
SDPLKRNAVI MGRKTWESIP IQHRPLPGRL NVVLTRSGSF DIATVENVVI CGSMISALEL
LAGSPYCVSV EKVFVIGGGQ IYREALNAPG CDAVHITEIE EHIECDTFIP LLDESVFQPW
YSSFPLVENK IRYCFTTYVR VRNSVAELTS QTNGCSSDSK SDSGNFEIQN FSFLPKTVFE
KHEEYLYLGL VENIISNGVT KNDRTRTGTV SIFGCQMRFN LRKSFPLLTT KKVFWRGVVE
ELLWFISGST NAKILKEKGV NIWEGNGSRE YLDSIGLTDR EEGDLGPIYG FQWRHFGARY
TDMHADYSGQ GFDQLLDVIS KIKNNPDDRR IIQSAWNPSD LRLMALPPCH MFAQFYVANG
ELSCQMYQRS ADMGLGVPFN IAAYALLTCM IAHVCDLVPG DFVHSIGDAH VYSNHLSDLF
ETSFRMLPKT FPVLKINSGE KDIDSFEAAD FKLIGYDPHQ KIEMKMAV
