ID TYSY1_BACSH Reviewed; 279 AA. AC E0TVT6; O30395; O30396; P42326; DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot. DT 02-NOV-2010, sequence version 1. DT 27-MAR-2024, entry version 59. DE RecName: Full=Thymidylate synthase 1 {ECO:0000255|HAMAP-Rule:MF_00008}; DE Short=TS 1 {ECO:0000255|HAMAP-Rule:MF_00008}; DE Short=TSase 1 {ECO:0000255|HAMAP-Rule:MF_00008}; DE EC=2.1.1.45 {ECO:0000255|HAMAP-Rule:MF_00008}; DE AltName: Full=Thymidylate synthase A {ECO:0000303|PubMed:9648749}; DE Short=TS A {ECO:0000303|PubMed:9648749}; DE Short=TSase A {ECO:0000303|PubMed:9648749}; GN Name=thyA1 {ECO:0000255|HAMAP-Rule:MF_00008}; Synonyms=thyA; GN OrderedLocusNames=BSUW23_09080; OS Bacillus spizizenii (strain ATCC 23059 / NRRL B-14472 / W23) (Bacillus OS subtilis subsp. spizizenii). OC Bacteria; Bacillota; Bacilli; Bacillales; Bacillaceae; Bacillus. OX NCBI_TaxID=655816; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 23059 / NRRL B-14472 / W23; RX PubMed=21527469; DOI=10.1099/mic.0.048520-0; RA Zeigler D.R.; RT "The genome sequence of Bacillus subtilis subsp. spizizenii W23: insights RT into speciation within the B. subtilis complex and into the history of B. RT subtilis genetics."; RL Microbiology 157:2033-2041(2011). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 50-279. RC STRAIN=ATCC 23059 / NRRL B-14472 / W23; RX PubMed=9648749; DOI=10.1007/pl00008625; RA Tam N.H., Borriss R.; RT "Genes encoding thymidylate synthases A and B in the genus Bacillus are RT members of two distinct families."; RL Mol. Gen. Genet. 258:427-430(1998). 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; CP002183; ADM37862.1; -; Genomic_DNA. DR EMBL; AF004103; AAC26325.1; -; Genomic_DNA. DR PIR; I40494; I40494. DR RefSeq; WP_003221167.1; NC_014479.1. DR AlphaFoldDB; E0TVT6; -. DR SMR; E0TVT6; -. DR GeneID; 64303656; -. DR KEGG; bss:BSUW23_09080; -. DR HOGENOM; CLU_021669_0_0_9; -. DR UniPathway; UPA00575; -. DR Proteomes; UP000002233; 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..279 FT /note="Thymidylate synthase 1" FT /id="PRO_0000403664" FT ACT_SITE 161 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 141..142 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 181..184 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 184 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 192 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 222..224 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 149 FT /note="N -> S (in Ref. 2; AAC26325)" FT /evidence="ECO:0000305" SQ SEQUENCE 279 AA; 32890 MW; 9E808B8519B9E33C CRC64; MTQFDKQYNS IIKDIMNNGI SDEEFNVRTK WDSDGTPAHT LSVISKQMRF DNSEVPILTT KKVAWKTAIK ELLWIWQLKS NDVTELNKMG VHIWDQWKQE DGTIGHAYGF QLGKKNRNLN GEKVDQVDYL LHQLKNNPSS RRHITMLWNP DELDSMALTP CVYETQWYVK QGKLHLEVRA RSNDMALGNP FNVFQYNVLQ RMIAQVTGYE LGEYIFNIGD CHVYTRHIDN LKIQMEREQF EAPELWINPE VKDFYDFTID DFKLFNYKHG DKLLFEVAV //