ID DRTS_MIMIV Reviewed; 563 AA. AC Q5UQG3; DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot. DT 07-DEC-2004, sequence version 1. DT 27-MAR-2024, entry version 80. 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; GN OrderedLocusNames=MIMI_R497; OS Acanthamoeba polyphaga mimivirus (APMV). OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Megaviricetes; OC Imitervirales; Mimiviridae; Megamimivirinae; Mimivirus; OC Mimivirus bradfordmassiliense. OX NCBI_TaxID=212035; OH NCBI_TaxID=5757; Acanthamoeba polyphaga (Amoeba). RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Rowbotham-Bradford; RX PubMed=15486256; DOI=10.1126/science.1101485; RA Raoult D., Audic S., Robert C., Abergel C., Renesto P., Ogata H., RA La Scola B., Susan M., Claverie J.-M.; RT "The 1.2-megabase genome sequence of Mimivirus."; RL Science 306:1344-1350(2004). CC -!- FUNCTION: Bifunctional enzyme. Involved in de novo dTMP biosynthesis. CC Key enzyme in folate metabolism. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY653733; AAV50762.1; -; Genomic_DNA. DR RefSeq; YP_003987009.1; NC_014649.1. DR SMR; Q5UQG3; -. DR GeneID; 9925127; -. DR KEGG; vg:9925127; -. DR OrthoDB; 13491at10239; -. DR UniPathway; UPA00077; UER00158. DR Proteomes; UP000001134; Genome. 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; 3.40.430.10; 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; 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:SF2; THYMIDYLATE SYNTHASE; 1. DR PANTHER; PTHR11548; THYMIDYLATE SYNTHASE 1; 1. DR Pfam; PF00186; DHFR_1; 1. DR Pfam; PF00303; Thymidylat_synt; 1. DR PRINTS; PR00108; THYMDSNTHASE. DR SUPFAM; SSF53597; Dihydrofolate reductase-like; 1. DR SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 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..563 FT /note="Bifunctional dihydrofolate reductase-thymidylate FT synthase" FT /id="PRO_0000186360" FT DOMAIN 3..195 FT /note="DHFR" FT REGION 275..563 FT /note="Thymidylate synthase" FT /evidence="ECO:0000250" FT ACT_SITE 435 FT /evidence="ECO:0000250" FT BINDING 117..124 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 292 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /evidence="ECO:0000250" FT BINDING 436 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /evidence="ECO:0000250" FT BINDING 464..468 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /evidence="ECO:0000250" FT BINDING 474 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /evidence="ECO:0000250" FT BINDING 504..506 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /evidence="ECO:0000250" SQ SEQUENCE 563 AA; 65063 MW; 590F4EAE5A11625B CRC64; MKKFNIIAAI NNDSIIGVKE YGTFSMPWPY LKDDMNHFRK ITTDTGSIES GVNAIIVGFN TWQTLPSSYR NIRSRFNIVI SRDDETDGQF HKYVKTFDEA IEFASSLTNL NEIFVIGGGV IYDLALKHKL LDKLYLTHVG SNYPIDDNVE KVVHFPLTWS KIEKMCDSNF LELDSEISKH DIGKNILLRF QEYSVKKELY WAIEYLKKNT SLDNKGIIGD KGATGSKGYS LEQHDYYSTE YFWNFYEFIT RKVFDLFNSS NEISIPSEEC PENQYIELVK TIMEKGIVKQ TRNSITKSIF GYQLKYDLSK GYPIQTIKRS YPKAIFEELM WMIRGQTDVS ILQKKGVHVW DKNSSKDFLS KYNLPYEEGD IGPGYGFQMR YWGAEYTDCK TSYQGQGIDQ LNKCIESIQN NPHDRRIMIN LWNCSDLDKM ALAPCHFCYM FGVDLYEVPT TSGKKGRLNC HLVQRSWDVL LGWNTTTAAL LTYLIANHCD LDPGILVHSI SDAHIYQSHI DSGAISQLLQ RKCRKFPNLV IRNKKEKIDD YEFDDLIIEN YYPCPSISAE MIA //