ID TYSY_METPP Reviewed; 283 AA. AC A2SHH0; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 06-MAR-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=Mpe_A2051; OS Methylibium petroleiphilum (strain ATCC BAA-1232 / LMG 22953 / PM1). OC Bacteria; Pseudomonadota; Betaproteobacteria; Burkholderiales; OC Sphaerotilaceae; Methylibium. OX NCBI_TaxID=420662; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC BAA-1232 / LMG 22953 / PM1; RX PubMed=17158667; DOI=10.1128/jb.01259-06; RA Kane S.R., Chakicherla A.Y., Chain P.S.G., Schmidt R., Shin M.W., RA Legler T.C., Scow K.M., Larimer F.W., Lucas S.M., Richardson P.M., RA Hristova K.R.; RT "Whole-genome analysis of the methyl tert-butyl ether-degrading beta- RT proteobacterium Methylibium petroleiphilum PM1."; RL J. Bacteriol. 189:1931-1945(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; CP000555; ABM95009.1; -; Genomic_DNA. DR RefSeq; WP_011829646.1; NC_008825.1. DR AlphaFoldDB; A2SHH0; -. DR SMR; A2SHH0; -. DR STRING; 420662.Mpe_A2051; -. DR KEGG; mpt:Mpe_A2051; -. DR eggNOG; COG0207; Bacteria. DR HOGENOM; CLU_021669_0_0_4; -. DR UniPathway; UPA00575; -. DR Proteomes; UP000000366; 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; 2. 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..283 FT /note="Thymidylate synthase" FT /id="PRO_0000321471" FT ACT_SITE 158 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 33 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 63 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 138..139 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 185..188 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 188 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 196 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 226..228 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 282 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 283 AA; 31957 MW; 336F46A78B742935 CRC64; MSALPSPSPR PARSQYEDFL RHVRDHGVVK ADRTGTGTTS VFGHQMRFDL REGFPLVTTK KVHLKSIVLE LLWFLRGDGN ATWLQERGVT IWDEWAAPDG DLGPVYGVQW RSWPTPDGGH VDQIAEVVKQ LKTNPDSRRI IVSAWNVADL PKMALMPCHA FFQFYVAPGD SPSARGRLSC QLYQRSADIF LGVPFNIASY ALLTHMLAQQ CDLEVGDFVW TGGDCHIYSN HREQVELQLS RAPRPYPTLQ IKRRPPSIFD YAYEDFEIIG YDPHPAIKAP VAV //