ID TYSY_FLAPJ Reviewed; 274 AA. AC A6GWH3; DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot. DT 24-JUL-2007, sequence version 1. DT 27-MAR-2024, entry version 82. 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=FP0333; OS Flavobacterium psychrophilum (strain ATCC 49511 / DSM 21280 / CIP 103535 / OS JIP02/86). OC Bacteria; Bacteroidota; Flavobacteriia; Flavobacteriales; OC Flavobacteriaceae; Flavobacterium. OX NCBI_TaxID=402612; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 49511 / DSM 21280 / CIP 103535 / JIP02/86; RX PubMed=17592475; DOI=10.1038/nbt1313; RA Duchaud E., Boussaha M., Loux V., Bernardet J.-F., Michel C., Kerouault B., RA Mondot S., Nicolas P., Bossy R., Caron C., Bessieres P., Gibrat J.-F., RA Claverol S., Dumetz F., Le Henaff M., Benmansour A.; RT "Complete genome sequence of the fish pathogen Flavobacterium RT psychrophilum."; RL Nat. Biotechnol. 25:763-769(2007). 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; AM398681; CAL42446.1; -; Genomic_DNA. DR RefSeq; WP_011962504.1; NC_009613.3. DR RefSeq; YP_001295264.1; NC_009613.3. DR AlphaFoldDB; A6GWH3; -. DR SMR; A6GWH3; -. DR STRING; 402612.FP0333; -. DR EnsemblBacteria; CAL42446; CAL42446; FP0333. DR GeneID; 66551467; -. DR KEGG; fps:FP0333; -. DR PATRIC; fig|402612.5.peg.344; -. DR eggNOG; COG0207; Bacteria. DR HOGENOM; CLU_021669_0_0_10; -. DR OrthoDB; 9774633at2; -. DR UniPathway; UPA00575; -. DR Proteomes; UP000006394; 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 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. PE 3: Inferred from homology; KW Cytoplasm; Methyltransferase; Nucleotide biosynthesis; Reference proteome; KW Transferase. FT CHAIN 1..274 FT /note="Thymidylate synthase" FT /id="PRO_1000000596" FT ACT_SITE 156 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 123..124 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 176..179 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 179 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 187 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 217..219 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 273 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 274 AA; 31299 MW; D61ECAE1E7C09E5D CRC64; MKQYLDLVKY VLNNGTQKGD RTGTGTKSVF GYQMRFNLAE GFPMVTTKKL HLKSIIHELL WFLKGETNIA YLQQNGVKIW DDWADENGEL GPVYGHQWRN WNNEEIDQIT ELIETLKINP NSRRMLVSAW NPSVLPDTTK SFAENVANAK VALPPCHAFF QFYVSEGKLS CQLYQRSADI FLGVPFNIAS YALFTMMIAQ VCDLQAGEFI HTFGDAHIYN NHFEQVALQL SREPKPLPKM ILNPAVKNIF DFKFEDFKLE GYESHAHIKG AVAV //