ID TYSY_STRP3 Reviewed; 279 AA. AC P0DG66; P67052; Q9A092; DT 27-JUL-2011, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 1. DT 27-MAR-2024, entry version 51. 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=SpyM3_0601; OS Streptococcus pyogenes serotype M3 (strain ATCC BAA-595 / MGAS315). OC Bacteria; Bacillota; Bacilli; Lactobacillales; Streptococcaceae; OC Streptococcus. OX NCBI_TaxID=198466; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC BAA-595 / MGAS315; RX PubMed=12122206; DOI=10.1073/pnas.152298499; RA Beres S.B., Sylva G.L., Barbian K.D., Lei B., Hoff J.S., Mammarella N.D., RA Liu M.-Y., Smoot J.C., Porcella S.F., Parkins L.D., Campbell D.S., RA Smith T.M., McCormick J.K., Leung D.Y.M., Schlievert P.M., Musser J.M.; RT "Genome sequence of a serotype M3 strain of group A Streptococcus: phage- RT encoded toxins, the high-virulence phenotype, and clone emergence."; RL Proc. Natl. Acad. Sci. U.S.A. 99:10078-10083(2002). 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 -!- SEQUENCE CAUTION: CC Sequence=AAM79208.1; Type=Erroneous initiation; Evidence={ECO:0000305}; 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; AE014074; AAM79208.1; ALT_INIT; Genomic_DNA. DR RefSeq; WP_010922172.1; NC_004070.1. DR AlphaFoldDB; P0DG66; -. DR SMR; P0DG66; -. DR KEGG; spg:SpyM3_0601; -. DR HOGENOM; CLU_021669_0_0_9; -. DR UniPathway; UPA00575; -. DR Proteomes; UP000000564; 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 PANTHER; PTHR11548; THYMIDYLATE SYNTHASE 1; 1. DR PANTHER; PTHR11548:SF1; THYMIDYLATE SYNTHASE-RELATED; 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..279 FT /note="Thymidylate synthase" FT /id="PRO_0000141033" FT ACT_SITE 154 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 133..134 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 178..181 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 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 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 219..221 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 278 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 279 AA; 32663 MW; 6D8B39FA88091AC8 CRC64; MTKADQIFKA NIQKIINEGS LSEQARPKYK DGRTAHSKYI TGAFAEYDLA KGEFPITTLR PIPIKSAIKE LFWIYQDQSN SLDVLEAKYN VHYWNEWEVD QTRTIGQRYG AVVKKHDIIS KILKQLAENP WNRRNVISLW DYEAFEETKG LLPCAFQIMF DVRRVGEDLY LDASLTQRSN DILVAHHINA MQYVALQMMI AKHFGWKIGK FFYFVNNLHI YDNQFDQAQE LLKRQPVASQ PKLVLNVPDR TNFFDIKPDD FELQNYDPVK PQLHFDLAI //