ID   TYSY_VIBPA              Reviewed;         283 AA.
AC   Q87SA0;
DT   23-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT   23-MAY-2003, sequence version 1.
DT   27-MAR-2024, entry version 104.
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=VP0524;
OS   Vibrio parahaemolyticus serotype O3:K6 (strain RIMD 2210633).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC   Vibrio.
OX   NCBI_TaxID=223926;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=RIMD 2210633;
RX   PubMed=12620739; DOI=10.1016/s0140-6736(03)12659-1;
RA   Makino K., Oshima K., Kurokawa K., Yokoyama K., Uda T., Tagomori K.,
RA   Iijima Y., Najima M., Nakano M., Yamashita A., Kubota Y., Kimura S.,
RA   Yasunaga T., Honda T., Shinagawa H., Hattori M., Iida T.;
RT   "Genome sequence of Vibrio parahaemolyticus: a pathogenic mechanism
RT   distinct from that of V. cholerae.";
RL   Lancet 361:743-749(2003).
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}.
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DR   EMBL; BA000031; BAC58787.1; -; Genomic_DNA.
DR   RefSeq; NP_796903.1; NC_004603.1.
DR   RefSeq; WP_005481388.1; NC_004603.1.
DR   AlphaFoldDB; Q87SA0; -.
DR   SMR; Q87SA0; -.
DR   GeneID; 1187992; -.
DR   KEGG; vpa:VP0524; -.
DR   PATRIC; fig|223926.6.peg.499; -.
DR   eggNOG; COG0207; Bacteria.
DR   HOGENOM; CLU_021669_0_1_6; -.
DR   UniPathway; UPA00575; -.
DR   Proteomes; UP000002493; Chromosome 1.
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..283
FT                   /note="Thymidylate synthase"
FT                   /id="PRO_0000141041"
FT   ACT_SITE        160
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT   BINDING         22
FT                   /ligand="dUMP"
FT                   /ligand_id="ChEBI:CHEBI:246422"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT   BINDING         180..183
FT                   /ligand="dUMP"
FT                   /ligand_id="ChEBI:CHEBI:246422"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT   BINDING         183
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         191
FT                   /ligand="dUMP"
FT                   /ligand_id="ChEBI:CHEBI:246422"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT   BINDING         221..223
FT                   /ligand="dUMP"
FT                   /ligand_id="ChEBI:CHEBI:246422"
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;  32780 MW;  BFE25A7962F6EBC9 CRC64;
     MKQYLDLCQR IVDQGVWVEN ERTGKRCLTV INADLTYDVA NNQFPLVTTR KSFWKAAVAE
     LLGYIRGYDN AEDFRKLGTK TWDANANLND AWLNNPYRKG EDDMGRVYGV QGRAWAKPDG
     GHIDQLRKIV DDLTRGVDDR GEILNFYNPG EFHMGCLRPC MYSHHFSLLD DTLYLNSTQR
     SCDVPLGLNF NMVQVYVFLA IMAQITGKKP GQAFHKIVNA HIYEDQLELM RDVQLKREPL
     QAPTFHINPE IKSLEDLETW VTLDDFWVEG YEHHDPIRYP FSV
//