ID TYSY_LACAC Reviewed; 318 AA. AC Q5FKL6; DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2005, sequence version 1. DT 27-MAR-2024, entry version 98. 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=LBA0901; OS Lactobacillus acidophilus (strain ATCC 700396 / NCK56 / N2 / NCFM). OC Bacteria; Bacillota; Bacilli; Lactobacillales; Lactobacillaceae; OC Lactobacillus. OX NCBI_TaxID=272621; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 700396 / NCK56 / N2 / NCFM; RX PubMed=15671160; DOI=10.1073/pnas.0409188102; RA Altermann E., Russell W.M., Azcarate-Peril M.A., Barrangou R., Buck B.L., RA McAuliffe O., Souther N., Dobson A., Duong T., Callanan M., Lick S., RA Hamrick A., Cano R., Klaenhammer T.R.; RT "Complete genome sequence of the probiotic lactic acid bacterium RT Lactobacillus acidophilus NCFM."; RL Proc. Natl. Acad. Sci. U.S.A. 102:3906-3912(2005). 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; CP000033; AAV42758.1; -; Genomic_DNA. DR RefSeq; WP_003546979.1; NC_006814.3. DR RefSeq; YP_193789.1; NC_006814.3. DR AlphaFoldDB; Q5FKL6; -. DR SMR; Q5FKL6; -. DR STRING; 272621.LBA0901; -. DR GeneID; 56942525; -. DR KEGG; lac:LBA0901; -. DR PATRIC; fig|272621.13.peg.859; -. DR eggNOG; COG0207; Bacteria. DR HOGENOM; CLU_021669_0_0_9; -. DR OrthoDB; 9774633at2; -. DR BioCyc; LACI272621:G1G49-908-MONOMER; -. DR UniPathway; UPA00575; -. DR Proteomes; UP000006381; 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 3: Inferred from homology; KW Cytoplasm; Methyltransferase; Nucleotide biosynthesis; Reference proteome; KW Transferase. FT CHAIN 1..318 FT /note="Thymidylate synthase" FT /id="PRO_0000140966" FT ACT_SITE 200 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 25 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 180..181 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 220..223 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 223 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 231 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 261..263 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; 37084 MW; C435502D5249CA2B CRC64; MAILEQPYLD LINKIMIEGH DKNDRTGTGT RSYFGAQMRF DLSKGFPILT TKKVPFGLIK SELLWFLRGD TNIRFLLEHK NHIWDEWAFK NWVNSDEYTG PDMTDFGLRS QSDPEFNKIY QAELKKFDRR ILDDENFAKK YGNLGDVYGA QWRHWQKRDG SFIDQIENVI EQIKNNPDSR RMIVTAWNPE DVPTSALPPC HVMFQFYVVD GKISVQLYQR SGDMFLGVPF NIASYALLLN MIARETGLQV GEFIHTLGDA HIYSNHFSQV KEMLSRKPYE SPQLWLNPEK KHIEDFDMQD IKLVDYKHHG TIKAPVAV //