ID TYSY_RHIWR Reviewed; 308 AA. AC A5VCW6; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 10-JUL-2007, sequence version 1. DT 27-MAR-2024, entry version 92. 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=Swit_3787; OS Rhizorhabdus wittichii (strain DSM 6014 / CCUG 31198 / JCM 15750 / NBRC OS 105917 / EY 4224 / RW1) (Sphingomonas wittichii). OC Bacteria; Pseudomonadota; Alphaproteobacteria; Sphingomonadales; OC Sphingomonadaceae; Rhizorhabdus. OX NCBI_TaxID=392499; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=DSM 6014 / CCUG 31198 / JCM 15750 / NBRC 105917 / EY 4224 / RC RW1; RG US DOE Joint Genome Institute; RA Copeland A., Lucas S., Lapidus A., Barry K., Glavina del Rio T., Dalin E., RA Tice H., Pitluck S., Saunders E., Brettin T., Bruce D., Detter J.C., RA Han C., Tapia R., Gilna P., Schmutz J., Larimer F., Land M., Hauser L., RA Kyrpides N., Kim E., Halden R.U., Miller T.R., Salzberg S.L., Eisen J.A., RA Richardson P.; RT "Complete sequence of chromosome of Sphingomonas wittichii RW1."; RL Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases. 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; CP000699; ABQ70132.1; -; Genomic_DNA. DR AlphaFoldDB; A5VCW6; -. DR SMR; A5VCW6; -. DR STRING; 392499.Swit_3787; -. DR PaxDb; 392499-Swit_3787; -. DR KEGG; swi:Swit_3787; -. DR eggNOG; COG0207; Bacteria. DR HOGENOM; CLU_021669_0_0_5; -. DR OrthoDB; 9774633at2; -. DR UniPathway; UPA00575; -. DR Proteomes; UP000001989; 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; 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..308 FT /note="Thymidylate synthase" FT /id="PRO_0000321483" FT ACT_SITE 190 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 170..171 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 210..213 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 213 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 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 251..253 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 307 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 308 AA; 34966 MW; 66AD3DFB498742B8 CRC64; MTEHPEQQYL DAMARAWYGG DERVDRTGVG TKSLFGVTMR FDLSDGTVPL ITTKKIFWKS AIKELIWFLS GDTNIRPLVM QNVHIWTDWP LDKYRKATGE AIDRDAFERR IVDDPAFAAE WGDLGPVYGK QWVDWPRYTP AGDGLFRREE KGVNQIAELV GMLRANPSSR RLIFTGWNVP ELPGMALPPC HMTYQYHVAG GRLSGILYQR SCDLGLGFPF NIFEAAVLIR MLAQQADLEP GELVWMGADT HVYSNHGHLV EEQLSRSPRP FPRLSLARKP ADMFSYALDD FVIEGYDPHP HIKAEVAV //