ID TYSY_LIMRD Reviewed; 320 AA. AC A5VJK9; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 10-JUL-2007, sequence version 1. DT 27-MAR-2024, entry version 93. 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=Lreu_0769; OS Limosilactobacillus reuteri (strain DSM 20016) (Lactobacillus reuteri). OC Bacteria; Bacillota; Bacilli; Lactobacillales; Lactobacillaceae; OC Limosilactobacillus. OX NCBI_TaxID=557436; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=DSM 20016; RX PubMed=21379339; DOI=10.1371/journal.pgen.1001314; RA Frese S.A., Benson A.K., Tannock G.W., Loach D.M., Kim J., Zhang M., RA Oh P.L., Heng N.C., Patil P.B., Juge N., Mackenzie D.A., Pearson B.M., RA Lapidus A., Dalin E., Tice H., Goltsman E., Land M., Hauser L., Ivanova N., RA Kyrpides N.C., Walter J.; RT "The evolution of host specialization in the vertebrate gut symbiont RT Lactobacillus reuteri."; RL PLoS Genet. 7:E1001314-E1001314(2011). 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=(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; 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; CP000705; ABQ83033.1; -; Genomic_DNA. DR RefSeq; WP_003668102.1; NZ_AZDD01000015.1. DR AlphaFoldDB; A5VJK9; -. DR SMR; A5VJK9; -. DR STRING; 557436.Lreu_0769; -. DR KEGG; lre:Lreu_0769; -. DR PATRIC; fig|557436.17.peg.459; -. DR eggNOG; COG0207; Bacteria. DR HOGENOM; CLU_021669_0_0_9; -. DR UniPathway; UPA00575; -. DR Proteomes; UP000001991; Chromosome. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. 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-UniPathway. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR CDD; cd00351; TS_Pyrimidine_HMase; 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; TIGR03284; thym_sym; 1. DR PANTHER; PTHR11548:SF9; THYMIDYLATE SYNTHASE; 1. DR PANTHER; PTHR11548; 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; Reference proteome; KW Transferase. FT CHAIN 1..320 FT /note="Thymidylate synthase" FT /id="PRO_0000321469" FT ACT_SITE 202 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 27 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 182..183 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 222..225 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 225 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 233 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 263..265 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 319 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 320 AA; 36982 MW; C50E1CE992A306EA CRC64; MATNVNEEQY LDLIRYVLAN GHQKGDRTGT GTKSVFGYQM RFDLSKGFPI LTTKKVPFGL IKSELLWFLR GDTNIRFLLQ HKNHIWDEWA FKKWVESDEY QGPDMTDFGH RWLKDPEFKQ VYLQEKKAFC QRILEDDDFA QKYGDLGLVY GSQWRKWKTS QGDTIDQIAN VIQQIKTTPD SRRMIVSAWN PEDVPSMALP PCHTMFQFYV NDGKLSCQLY QRSADIFLGV PFNIASYALL THMIAHQCGL EPGEFVHTLG DAHIYLNHLD QVKEQLTRTP HEAPKLILPA EPKPIDQYEM TDIKLEGYTH EPAIKAPVAV //