ID TYSY_LACLA Reviewed; 279 AA. AC P19368; Q9CFD8; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 27-APR-2001, sequence version 2. DT 27-MAR-2024, entry version 137. 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}; OrderedLocusNames=LL1541; GN ORFNames=L182559; OS Lactococcus lactis subsp. lactis (strain IL1403) (Streptococcus lactis). OC Bacteria; Bacillota; Bacilli; Lactobacillales; Streptococcaceae; OC Lactococcus. OX NCBI_TaxID=272623; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=712; RX PubMed=2117882; DOI=10.1128/aem.56.7.2156-2163.1990; RA Ross P., O'Gara F., Condon S.; RT "Cloning and characterization of the thymidylate synthase gene from RT Lactococcus lactis subsp. lactis."; RL Appl. Environ. Microbiol. 56:2156-2163(1990). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=IL1403; RX PubMed=11337471; DOI=10.1101/gr.gr-1697r; RA Bolotin A., Wincker P., Mauger S., Jaillon O., Malarme K., Weissenbach J., RA Ehrlich S.D., Sorokin A.; RT "The complete genome sequence of the lactic acid bacterium Lactococcus RT lactis ssp. lactis IL1403."; RL Genome Res. 11:731-753(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 -!- 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; M33770; AAA25221.1; -; Genomic_DNA. DR EMBL; AE005176; AAK05639.1; -; Genomic_DNA. DR PIR; A43797; A43797. DR PIR; E86817; E86817. DR RefSeq; NP_267697.1; NC_002662.1. DR RefSeq; WP_003130015.1; NC_002662.1. DR AlphaFoldDB; P19368; -. DR SMR; P19368; -. DR PaxDb; 272623-L182559; -. DR EnsemblBacteria; AAK05639; AAK05639; L182559. DR GeneID; 69713592; -. DR KEGG; lla:L182559; -. DR PATRIC; fig|272623.7.peg.1652; -. DR eggNOG; COG0207; Bacteria. DR HOGENOM; CLU_021669_0_0_9; -. DR OrthoDB; 9774633at2; -. DR UniPathway; UPA00575; -. DR Proteomes; UP000002196; 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; Reference proteome; KW Transferase. FT CHAIN 1..279 FT /note="Thymidylate synthase" FT /id="PRO_0000140969" FT ACT_SITE 153 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 132..133 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" FT CONFLICT 6..7 FT /note="KI -> QV (in Ref. 1; AAA25221)" FT /evidence="ECO:0000305" FT CONFLICT 34 FT /note="T -> M (in Ref. 1; AAA25221)" FT /evidence="ECO:0000305" FT CONFLICT 83..84 FT /note="AI -> SV (in Ref. 1; AAA25221)" FT /evidence="ECO:0000305" FT CONFLICT 123 FT /note="D -> E (in Ref. 1; AAA25221)" FT /evidence="ECO:0000305" FT CONFLICT 165 FT /note="Q -> K (in Ref. 1; AAA25221)" FT /evidence="ECO:0000305" FT CONFLICT 232 FT /note="V -> M (in Ref. 1; AAA25221)" FT /evidence="ECO:0000305" FT CONFLICT 238 FT /note="D -> E (in Ref. 1; AAA25221)" FT /evidence="ECO:0000305" SQ SEQUENCE 279 AA; 32499 MW; CE0B97935D8DA1F8 CRC64; MTYADKIFKQ NIQNILDNGV FSENARPKYK DGQTANSKYV TGSFVTYDLQ KGEFPITTLR PIPIKSAIKE LMWIYQDQTS ELAILEEKYG VKYWGEWGIG DGTIGQRYGA TVKKYNIIGK LLDGLAKNPW NRRNIINLWQ YEDFEETEGL LPCAFQTMFD VRREQDGQIY LDATLIQRSN DMLVAHHINA MQYVALQMMI AKHFSWKVGK FFYFVNNLHI YDNQFEQANE LVKRTASDKE PRLVLNVPDG TNFFDIKPED FELVDYEPVK PQLKFDLAI //