ID TYSY_POLSJ Reviewed; 284 AA. AC Q12CI6; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 22-AUG-2006, sequence version 1. DT 04-NOV-2026, entry version 107. DE RecName: Full=Thymidylate synthase {ECO:0000255|HAMAP-Rule:MF_00008}; DE Short=TS {ECO:0000255|HAMAP-Rule:MF_00008}; DE Short=TSase {ECO:0000255|HAMAP-Rule:MF_00008}; DE EC=2.1.1.45 {ECO:0000255|HAMAP-Rule:MF_00008}; GN Name=thyA {ECO:0000255|HAMAP-Rule:MF_00008}; GN OrderedLocusNames=Bpro_1823; OS Polaromonas sp. (strain JS666 / ATCC BAA-500). OC Bacteria; Pseudomonadati; Pseudomonadota; Betaproteobacteria; OC Burkholderiales; Comamonadaceae; Polaromonas. OX NCBI_TaxID=296591; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=JS666 / ATCC BAA-500; RX PubMed=18723656; DOI=10.1128/aem.00197-08; RA Mattes T.E., Alexander A.K., Richardson P.M., Munk A.C., Han C.S., RA Stothard P., Coleman N.V.; RT "The genome of Polaromonas sp. strain JS666: insights into the evolution of RT a hydrocarbon- and xenobiotic-degrading bacterium, and features of RT relevance to biotechnology."; RL Appl. Environ. Microbiol. 74:6405-6416(2008). CC -!- FUNCTION: Catalyzes the reductive methylation of 2'-deoxyuridine-5'- CC monophosphate (dUMP) to 2'-deoxythymidine-5'-monophosphate (dTMP) while CC utilizing 5,10-methylenetetrahydrofolate (mTHF) as the methyl donor and CC reductant in the reaction, yielding dihydrofolate (DHF) as a by- CC product. This enzymatic reaction provides an intracellular de novo CC source of dTMP, an essential precursor for DNA biosynthesis. CC {ECO:0000255|HAMAP-Rule:MF_00008}. CC -!- CATALYTIC ACTIVITY: CC Reaction=dUMP + (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate = 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; Evidence={ECO:0000255|HAMAP-Rule:MF_00008}; CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis. {ECO:0000255|HAMAP- CC Rule:MF_00008}. CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_00008}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00008}. CC -!- SIMILARITY: Belongs to the thymidylate synthase family. Bacterial-type CC ThyA subfamily. {ECO:0000255|HAMAP-Rule:MF_00008}. 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; CP000316; ABE43756.1; -; Genomic_DNA. DR RefSeq; WP_011482755.1; NC_007948.1. DR AlphaFoldDB; Q12CI6; -. DR SMR; Q12CI6; -. DR STRING; 296591.Bpro_1823; -. DR KEGG; pol:Bpro_1823; -. DR eggNOG; COG0207; Bacteria. DR HOGENOM; CLU_021669_0_0_4; -. DR OMA; AAHQWVT; -. DR OrthoDB; 9774633at2; -. DR UniPathway; UPA00575; -. DR GO; GO:0005829; C:cytosol; IEA:TreeGrafter. DR GO; GO:0004799; F:thymidylate synthase activity; IEA:UniProtKB-UniRule. DR GO; GO:0006231; P:dTMP biosynthetic process; IEA:UniProtKB-UniRule. DR GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniRule. DR CDD; cd00351; TS_Pyrimidine_HMase; 1. DR FunFam; 3.30.572.10:FF:000013; Thymidylate synthase; 1. DR Gene3D; 3.30.572.10; Thymidylate synthase/dCMP hydroxymethylase domain; 1. DR HAMAP; MF_00008; Thymidy_synth_bact; 1. 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; NF002497; PRK01827.1-3; 1. DR NCBIfam; NF002499; thyA; 1. DR NCBIfam; TIGR03284; thym_sym; 2. DR PANTHER; PTHR11548; THYMIDYLATE SYNTHASE 1; 1. DR PANTHER; PTHR11548:SF1; THYMIDYLATE SYNTHASE 1; 1. DR Pfam; PF00303; Thymidylat_synt; 1. DR PRINTS; PR00108; THYMDSNTHASE. DR SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 1. DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1. PE 3: Inferred from homology; KW Cytoplasm; Methyltransferase; Nucleotide biosynthesis; Transferase. FT CHAIN 1..284 FT /note="Thymidylate synthase" FT /id="PRO_0000321473" FT ACT_SITE 159 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 34 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 64 FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:15636" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 139..140 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 186..189 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 189 FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:15636" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 197 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 227..229 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 283 FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:15636" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" SQ SEQUENCE 284 AA; 32301 MW; 4D17892819F26951 CRC64; MNTPPETRPD RPIRSQYEDF MRHVDAHGVF KADRTGTGTK SVFGYQMRFD LNEGFPLVTT KKVHLKSIVQ ELLWFLTGSS DNNWLKERGV TIWDEWARED GDLGPVYGVQ WRSWPTPDGG HIDQISEVIK TLKTNPDSRR IIVSAWNVAD LSKMALMPCH AFFQFYVAPA TEAGGKGKLS CQLYQRSADI FLGVPFNIGS YALLTHMVAQ QCDLDVGDFI WTGGDCHIYS NHAEQVALQL SRAPFPYPTL HIKRKPESIF DYQFDDFEFL DYQHHAAIKA PVAV //