ID TYSY_STAAU Reviewed; 318 AA. AC P0A0M5; P13954; Q59907; DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 15-FEB-2005, sequence version 1. DT 13-SEP-2023, entry version 95. 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}; Synonyms=thyE, thyF; OS Staphylococcus aureus. OG Plasmid pSK1, and Plasmid pABU1. OC Bacteria; Bacillota; Bacilli; Bacillales; Staphylococcaceae; OC Staphylococcus. OX NCBI_TaxID=1280; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC PLASMID=pSK1; TRANSPOSON=Tn4003; RX PubMed=2548057; DOI=10.1111/j.1365-2958.1989.tb01805.x; RA Rouch D.A., Messeroti L.J., Loo L.S.L., Jackson C.A., Skurray R.A.; RT "Trimethoprim resistance transposon Tn4003 from Staphylococcus aureus RT encodes genes for a dihydrofolate reductase and thymidylate synthetase RT flanked by three copies of IS257."; RL Mol. Microbiol. 3:161-175(1989). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=157/4696; PLASMID=pABU1; RX PubMed=2365064; DOI=10.1016/0014-5793(90)81529-w; RA Burdeska A., Ott M., Bannwarth W., Then R.L.; RT "Identical genes for trimethoprim-resistant dihydrofolate reductase from RT Staphylococcus aureus in Australia and central Europe."; RL FEBS Lett. 266:159-162(1990). 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; X13290; CAA31648.1; -; Genomic_DNA. DR EMBL; Y07536; CAA68823.1; -; Genomic_DNA. DR PIR; S04163; YXSAT3. DR RefSeq; NP_877984.1; NC_005054.1. DR RefSeq; WP_000282655.1; NZ_VTZV01000057.1. DR RefSeq; YP_002790944.1; NC_012547.1. DR RefSeq; YP_003813114.1; NC_014369.1. DR RefSeq; YP_006937651.1; NC_013320.1. DR RefSeq; YP_006938353.1; NC_013338.1. DR AlphaFoldDB; P0A0M5; -. DR SMR; P0A0M5; -. DR GeneID; 50018757; -. DR OMA; WNEWEVG; -. DR UniPathway; UPA00575; -. 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; Plasmid; KW Transferase. FT CHAIN 1..318 FT /note="Thymidylate synthase" FT /id="PRO_0000141022" FT ACT_SITE 201 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 26 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 181..182 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 221..224 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 224 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 232 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 262..264 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 317 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 318 AA; 37178 MW; 4CE480445CF9653A CRC64; MYNPFDEAYH GLCEEILEIG NRRDDRTHTG TISKFGHQLR FDLTKGFPLL TTKKVSFKLV ATELLWFIKG DTNIQYLLKY NNNIWNEWAF ENYVQSDDYH GPDMTDFGHR SQQDPEFNEQ YKEEMKKFKE RILNDDAFAK KYGNLGNVYG KQWRDWEDKN GNHYDQLKSV IQQIKTNPNS RRHIVSAWNP TEIDSMALPP CHTMFQFYVQ EGKLNCQLYQ RSADIFLGVP FNIASYALLT HLVAKECGLE VGEFIHTFGD AHIYSNHMDA IHTQLSRDSY LPPQLKINTD KSIFDINYED LELINYESHP AIKAPIAV //