ID   TYSY_STAEP              Reviewed;          97 AA.
AC   P0C0M4; P0A0M4; P13954; Q59907;
DT   22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT   22-NOV-2005, sequence version 1.
DT   13-SEP-2023, entry version 68.
DE   RecName: Full=Thymidylate synthase {ECO:0000250|UniProtKB:P0A884};
DE            Short=TS {ECO:0000250|UniProtKB:P0A884};
DE            Short=TSase {ECO:0000250|UniProtKB:P0A884};
DE            EC=2.1.1.45 {ECO:0000250|UniProtKB:P0A884};
DE   Flags: Fragment;
GN   Name=thyA {ECO:0000250|UniProtKB:P0A884}; Synonyms=thyE, thyF;
OS   Staphylococcus epidermidis.
OC   Bacteria; Bacillota; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=1282;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 14990 / DSM 20044 / CIP 81.55 / NCTC 11047;
RX   PubMed=7768789; DOI=10.1128/jb.177.11.2965-2970.1995;
RA   Dale G.E., Broger C., Hartman P.G., Langen H., Page M.G.P., Then R.L.,
RA   Stueber D.;
RT   "Characterization of the gene for the chromosomal dihydrofolate reductase
RT   (DHFR) of Staphylococcus epidermidis ATCC 14990: the origin of the
RT   trimethoprim-resistant S1 DHFR from Staphylococcus aureus?";
RL   J. Bacteriol. 177:2965-2970(1995).
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:0000250|UniProtKB:P0A884}.
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:0000250|UniProtKB:P0A884};
CC   -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis.
CC       {ECO:0000250|UniProtKB:P0A884}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P0A884}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P0A884}.
CC   -!- SIMILARITY: Belongs to the thymidylate synthase family. Bacterial-type
CC       ThyA subfamily. {ECO:0000305}.
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DR   EMBL; Z48233; CAA88268.1; -; Genomic_DNA.
DR   PIR; S57628; S57628.
DR   AlphaFoldDB; P0C0M4; -.
DR   SMR; P0C0M4; -.
DR   UniPathway; UPA00575; -.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0004799; F:thymidylate synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006231; P:dTMP biosynthetic process; IEA:InterPro.
DR   GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.572.10; Thymidylate synthase/dCMP hydroxymethylase domain; 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   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   SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 1.
PE   3: Inferred from homology;
KW   Cytoplasm; Methyltransferase; Nucleotide biosynthesis; Transferase.
FT   CHAIN           <1..97
FT                   /note="Thymidylate synthase"
FT                   /id="PRO_0000141024"
FT   BINDING         1..3
FT                   /ligand="dUMP"
FT                   /ligand_id="ChEBI:CHEBI:246422"
FT                   /evidence="ECO:0000250|UniProtKB:P0A884"
FT   BINDING         3
FT                   /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:15636"
FT                   /evidence="ECO:0000250|UniProtKB:P0A884"
FT   BINDING         11
FT                   /ligand="dUMP"
FT                   /ligand_id="ChEBI:CHEBI:246422"
FT                   /evidence="ECO:0000250|UniProtKB:P0A884"
FT   BINDING         41..43
FT                   /ligand="dUMP"
FT                   /ligand_id="ChEBI:CHEBI:246422"
FT                   /evidence="ECO:0000250|UniProtKB:P0A884"
FT   BINDING         96
FT                   /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:15636"
FT                   /evidence="ECO:0000250|UniProtKB:P0A884"
FT   NON_TER         1
SQ   SEQUENCE   97 AA;  10843 MW;  0187C5934331B71F CRC64;
     SADIFLGVPF NIASYALLTH LVAKECGLEV GEFIHTFGDA HIYSNHMDAI HTQLSRDSYL
     PPQLKINTDK SIFDINYEDL ELINYESHPA IKAPIAV
//