ID TYSY_ECO57 Reviewed; 264 AA. AC P0A886; P00470; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 27-MAR-2024, entry version 120. 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=Z4144, ECs3684; OS Escherichia coli O157:H7. OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Enterobacteriaceae; Escherichia. OX NCBI_TaxID=83334; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=O157:H7 / EDL933 / ATCC 700927 / EHEC; RX PubMed=11206551; DOI=10.1038/35054089; RA Perna N.T., Plunkett G. III, Burland V., Mau B., Glasner J.D., Rose D.J., RA Mayhew G.F., Evans P.S., Gregor J., Kirkpatrick H.A., Posfai G., RA Hackett J., Klink S., Boutin A., Shao Y., Miller L., Grotbeck E.J., RA Davis N.W., Lim A., Dimalanta E.T., Potamousis K., Apodaca J., RA Anantharaman T.S., Lin J., Yen G., Schwartz D.C., Welch R.A., RA Blattner F.R.; RT "Genome sequence of enterohaemorrhagic Escherichia coli O157:H7."; RL Nature 409:529-533(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=O157:H7 / Sakai / RIMD 0509952 / EHEC; RX PubMed=11258796; DOI=10.1093/dnares/8.1.11; RA Hayashi T., Makino K., Ohnishi M., Kurokawa K., Ishii K., Yokoyama K., RA Han C.-G., Ohtsubo E., Nakayama K., Murata T., Tanaka M., Tobe T., Iida T., RA Takami H., Honda T., Sasakawa C., Ogasawara N., Yasunaga T., Kuhara S., RA Shiba T., Hattori M., Shinagawa H.; RT "Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and RT genomic comparison with a laboratory strain K-12."; RL DNA Res. 8:11-22(2001). 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 -!- PTM: The N-terminal is probably N-(dihydroxymethyl)-methionine, the CC hydrated form of N-formylmethionine. {ECO:0000250}. 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; AE005174; AAG57938.1; -; Genomic_DNA. DR EMBL; BA000007; BAB37107.1; -; Genomic_DNA. DR PIR; D91089; D91089. DR PIR; F85934; F85934. DR RefSeq; NP_311711.1; NC_002695.1. DR RefSeq; WP_000816232.1; NZ_VOAI01000003.1. DR PDB; 4LRR; X-ray; 2.41 A; A=1-264. DR PDBsum; 4LRR; -. DR AlphaFoldDB; P0A886; -. DR SMR; P0A886; -. DR STRING; 155864.Z4144; -. DR GeneID; 83579666; -. DR GeneID; 916501; -. DR KEGG; ece:Z4144; -. DR KEGG; ecs:ECs_3684; -. DR PATRIC; fig|386585.9.peg.3851; -. DR eggNOG; COG0207; Bacteria. DR HOGENOM; CLU_021669_0_0_6; -. DR OMA; IVYELLW; -. DR SABIO-RK; P0A886; -. DR UniPathway; UPA00575; -. DR Proteomes; UP000000558; Chromosome. DR Proteomes; UP000002519; 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; 2. 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; Formylation; Methyltransferase; KW Nucleotide biosynthesis; Reference proteome; Transferase. FT CHAIN 1..264 FT /note="Thymidylate synthase" FT /id="PRO_0000140955" FT ACT_SITE 146 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 21 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 51 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 126..127 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 166..169 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 169 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 177 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 207..209 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 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..14 FT /evidence="ECO:0007829|PDB:4LRR" FT STRAND 16..19 FT /evidence="ECO:0007829|PDB:4LRR" FT STRAND 25..37 FT /evidence="ECO:0007829|PDB:4LRR" FT HELIX 38..40 FT /evidence="ECO:0007829|PDB:4LRR" FT STRAND 46..48 FT /evidence="ECO:0007829|PDB:4LRR" FT HELIX 53..64 FT /evidence="ECO:0007829|PDB:4LRR" FT HELIX 70..74 FT /evidence="ECO:0007829|PDB:4LRR" FT TURN 79..83 FT /evidence="ECO:0007829|PDB:4LRR" FT HELIX 94..100 FT /evidence="ECO:0007829|PDB:4LRR" FT HELIX 111..121 FT /evidence="ECO:0007829|PDB:4LRR" FT STRAND 129..131 FT /evidence="ECO:0007829|PDB:4LRR" FT HELIX 135..140 FT /evidence="ECO:0007829|PDB:4LRR" FT STRAND 141..143 FT /evidence="ECO:0007829|PDB:4LRR" FT STRAND 146..155 FT /evidence="ECO:0007829|PDB:4LRR" FT STRAND 158..169 FT /evidence="ECO:0007829|PDB:4LRR" FT TURN 170..173 FT /evidence="ECO:0007829|PDB:4LRR" FT HELIX 174..191 FT /evidence="ECO:0007829|PDB:4LRR" FT STRAND 195..209 FT /evidence="ECO:0007829|PDB:4LRR" FT HELIX 210..212 FT /evidence="ECO:0007829|PDB:4LRR" FT HELIX 213..220 FT /evidence="ECO:0007829|PDB:4LRR" FT STRAND 229..232 FT /evidence="ECO:0007829|PDB:4LRR" FT HELIX 244..246 FT /evidence="ECO:0007829|PDB:4LRR" FT STRAND 247..251 FT /evidence="ECO:0007829|PDB:4LRR" SQ SEQUENCE 264 AA; 30480 MW; 0E6D88ED98D24D22 CRC64; MKQYLELMQK VLDEGTQKND RTGTGTLSIF GHQMRFNLQD GFPLVTTKRC HLRSIIHELL WFLQGDTNIA YLHENNVTIW DEWADENGDL GPVYGKQWRA WPTPDGRHID QITTVLNQLK NDPDSRRIIV SAWNVGELDK MALAPCHAFF QFYVADGKLS CQLYQRSCDV FLGLPFNIAS YALLVHMMAQ QCDLEVGDFV WTGGDTHLYS NHMDQTHLQL SREPRPLPKL IIKRKPESIF DYRFEDFEIE GYDPHPGIKA PVAI //