ID   TYSY_PHOPR              Reviewed;         283 AA.
AC   Q6LUM1;
DT   26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   27-MAR-2024, entry version 108.
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=PBPRA0581;
OS   Photobacterium profundum (strain SS9).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC   Photobacterium.
OX   NCBI_TaxID=298386;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-1253 / SS9;
RX   PubMed=15746425; DOI=10.1126/science.1103341;
RA   Vezzi A., Campanaro S., D'Angelo M., Simonato F., Vitulo N., Lauro F.M.,
RA   Cestaro A., Malacrida G., Simionati B., Cannata N., Romualdi C.,
RA   Bartlett D.H., Valle G.;
RT   "Life at depth: Photobacterium profundum genome sequence and expression
RT   analysis.";
RL   Science 307:1459-1461(2005).
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; CR378664; CAG19004.1; -; Genomic_DNA.
DR   RefSeq; WP_011217355.1; NC_006370.1.
DR   AlphaFoldDB; Q6LUM1; -.
DR   SMR; Q6LUM1; -.
DR   STRING; 298386.PBPRA0581; -.
DR   KEGG; ppr:PBPRA0581; -.
DR   eggNOG; COG0207; Bacteria.
DR   HOGENOM; CLU_021669_0_1_6; -.
DR   UniPathway; UPA00575; -.
DR   Proteomes; UP000000593; 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_0000141001"
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;  32372 MW;  2EB8981EBDD1854C CRC64;
     MKQYLELCQR IVDDGVWIEN KRTNKRCLTV VNADLTFDVA NNQFPLITTR KSFWKSAIAE
     LLGYIRGYDN AADFRALGTK TWDMNANDNL AWLNNPHRKG EDDMGRVYGV QGRSWQKPDG
     STIDQLRKIV DNLSEGIDDR GEILTFYNPG EFDLGCLRPC MHTHTFSLLG DTLHLTSYQR
     SCDVPLGLNF NQVQVYTLLA LVAQITGKKP GLAYHKIINA HIYEDQLSLL RDVQLTRTPF
     AAPKLIINPK IKCLEDLETW VTMDDFDVIG YEHHEAIKYP FSV
//