ID TYSY_ENTFA Reviewed; 315 AA. AC Q834R3; DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 1. DT 27-MAR-2024, entry version 123. 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=EF_1576; OS Enterococcus faecalis (strain ATCC 700802 / V583). OC Bacteria; Bacillota; Bacilli; Lactobacillales; Enterococcaceae; OC Enterococcus. OX NCBI_TaxID=226185; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 700802 / V583; RX PubMed=12663927; DOI=10.1126/science.1080613; RA Paulsen I.T., Banerjei L., Myers G.S.A., Nelson K.E., Seshadri R., RA Read T.D., Fouts D.E., Eisen J.A., Gill S.R., Heidelberg J.F., Tettelin H., RA Dodson R.J., Umayam L.A., Brinkac L.M., Beanan M.J., Daugherty S.C., RA DeBoy R.T., Durkin S.A., Kolonay J.F., Madupu R., Nelson W.C., RA Vamathevan J.J., Tran B., Upton J., Hansen T., Shetty J., Khouri H.M., RA Utterback T.R., Radune D., Ketchum K.A., Dougherty B.A., Fraser C.M.; RT "Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus RT faecalis."; RL Science 299:2071-2074(2003). 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; AE016830; AAO81363.1; -; Genomic_DNA. DR RefSeq; NP_815293.1; NC_004668.1. DR RefSeq; WP_002357569.1; NZ_KE136528.1. DR PDB; 3UWL; X-ray; 2.07 A; A/B/C/D=1-315. DR PDB; 4O7U; X-ray; 2.40 A; A/B/C/D=1-315. DR PDB; 5J7W; X-ray; 2.50 A; A/B/C/D=1-315. DR PDB; 6QXS; X-ray; 2.88 A; A/B/C/D=1-315. DR PDB; 6QYA; X-ray; 1.76 A; A/B/C/D=1-315. DR PDBsum; 3UWL; -. DR PDBsum; 4O7U; -. DR PDBsum; 5J7W; -. DR PDBsum; 6QXS; -. DR PDBsum; 6QYA; -. DR AlphaFoldDB; Q834R3; -. DR SMR; Q834R3; -. DR STRING; 226185.EF_1576; -. DR BindingDB; Q834R3; -. DR ChEMBL; CHEMBL1795144; -. DR DrugCentral; Q834R3; -. DR EnsemblBacteria; AAO81363; AAO81363; EF_1576. DR GeneID; 60893881; -. DR KEGG; efa:EF1576; -. DR PATRIC; fig|226185.45.peg.1929; -. DR eggNOG; COG0207; Bacteria. DR HOGENOM; CLU_021669_0_2_9; -. DR BRENDA; 2.1.1.45; 2095. DR UniPathway; UPA00575; -. DR Proteomes; UP000001415; 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 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Methyltransferase; Nucleotide biosynthesis; KW Reference proteome; Transferase. FT CHAIN 1..315 FT /note="Thymidylate synthase" FT /id="PRO_0000140957" FT ACT_SITE 197 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 22 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 177..178 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 217..220 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 220 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 228 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 258..260 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 314 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 HELIX 2..15 FT /evidence="ECO:0007829|PDB:6QYA" FT STRAND 17..19 FT /evidence="ECO:0007829|PDB:6QYA" FT STRAND 27..38 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 39..41 FT /evidence="ECO:0007829|PDB:6QYA" FT STRAND 47..49 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 53..64 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 71..75 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 82..89 FT /evidence="ECO:0007829|PDB:6QYA" FT STRAND 92..94 FT /evidence="ECO:0007829|PDB:3UWL" FT HELIX 103..109 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 111..115 FT /evidence="ECO:0007829|PDB:4O7U" FT TURN 127..129 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 135..138 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 145..150 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 162..172 FT /evidence="ECO:0007829|PDB:6QYA" FT STRAND 180..182 FT /evidence="ECO:0007829|PDB:6QYA" FT TURN 186..188 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 189..191 FT /evidence="ECO:0007829|PDB:6QYA" FT STRAND 192..194 FT /evidence="ECO:0007829|PDB:6QYA" FT STRAND 197..206 FT /evidence="ECO:0007829|PDB:6QYA" FT STRAND 209..220 FT /evidence="ECO:0007829|PDB:6QYA" FT TURN 221..224 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 225..242 FT /evidence="ECO:0007829|PDB:6QYA" FT STRAND 246..260 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 261..263 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 264..271 FT /evidence="ECO:0007829|PDB:6QYA" FT STRAND 280..283 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 290..292 FT /evidence="ECO:0007829|PDB:6QYA" FT HELIX 295..297 FT /evidence="ECO:0007829|PDB:6QYA" FT STRAND 298..302 FT /evidence="ECO:0007829|PDB:6QYA" SQ SEQUENCE 315 AA; 36344 MW; 0593A11D77D2D0A2 CRC64; MEEAYLALGK KILEEGHFKE DRTGTGTYSL FGYQMRFDLA KGFPLLTTKR VPFGLIKSEL LWFLKGDTNI RYLLERNNHI WDEWAFERYV KSADYQGPDM TDFGHRVLQD PAFAEQYKEE HQKFCDAILN DAEFAEKYGE LGNIYGAQWR HWETKDGSFI DQLANVIEMI KTNPDSRRLI VSAWNPEDVP SMALPPCHTM FQFYVNEGKL SCQLYQRSAD VFLGVPFNIA SYALLTHLIA HETGLEVGEF VHTLGDAHLY QNHVEQMQEQ LSREVRSFPT LVLNPDKASV FDFDMEDIKV EGYDPHPTIK APIAV //