TYSY_STAAU
ID TYSY_STAAU Reviewed; 318 AA.
AC P0A0M5; P13954; Q59907;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 91.
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}; Synonyms=thyE, thyF;
OS Staphylococcus aureus.
OG Plasmid pSK1, and Plasmid pABU1.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1280;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC PLASMID=pSK1; TRANSPOSON=Tn4003;
RX PubMed=2548057; DOI=10.1111/j.1365-2958.1989.tb01805.x;
RA Rouch D.A., Messeroti L.J., Loo L.S.L., Jackson C.A., Skurray R.A.;
RT "Trimethoprim resistance transposon Tn4003 from Staphylococcus aureus
RT encodes genes for a dihydrofolate reductase and thymidylate synthetase
RT flanked by three copies of IS257.";
RL Mol. Microbiol. 3:161-175(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=157/4696; PLASMID=pABU1;
RX PubMed=2365064; DOI=10.1016/0014-5793(90)81529-w;
RA Burdeska A., Ott M., Bannwarth W., Then R.L.;
RT "Identical genes for trimethoprim-resistant dihydrofolate reductase from
RT Staphylococcus aureus in Australia and central Europe.";
RL FEBS Lett. 266:159-162(1990).
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; X13290; CAA31648.1; -; Genomic_DNA.
DR EMBL; Y07536; CAA68823.1; -; Genomic_DNA.
DR PIR; S04163; YXSAT3.
DR RefSeq; NP_877984.1; NC_005054.1.
DR RefSeq; WP_000282655.1; NZ_VTZV01000057.1.
DR RefSeq; YP_002790944.1; NC_012547.1.
DR RefSeq; YP_003813114.1; NC_014369.1.
DR RefSeq; YP_006937651.1; NC_013320.1.
DR RefSeq; YP_006938353.1; NC_013338.1.
DR AlphaFoldDB; P0A0M5; -.
DR SMR; P0A0M5; -.
DR GeneID; 50018757; -.
DR OMA; WNEWEVG; -.
DR UniPathway; UPA00575; -.
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; -; 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 PANTHER; PTHR11548; PTHR11548; 1.
DR Pfam; PF00303; Thymidylat_synt; 1.
DR PRINTS; PR00108; THYMDSNTHASE.
DR SUPFAM; SSF55831; SSF55831; 1.
DR TIGRFAMs; TIGR03284; thym_sym; 1.
DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE 3: Inferred from homology;
KW Cytoplasm; Methyltransferase; Nucleotide biosynthesis; Plasmid;
KW Transferase.
FT CHAIN 1..318
FT /note="Thymidylate synthase"
FT /id="PRO_0000141022"
FT ACT_SITE 201
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT BINDING 26
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 181..182
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 221..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 224
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 232
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 262..264
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 317
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 318 AA; 37178 MW; 4CE480445CF9653A CRC64;
MYNPFDEAYH GLCEEILEIG NRRDDRTHTG TISKFGHQLR FDLTKGFPLL TTKKVSFKLV
ATELLWFIKG DTNIQYLLKY NNNIWNEWAF ENYVQSDDYH GPDMTDFGHR SQQDPEFNEQ
YKEEMKKFKE RILNDDAFAK KYGNLGNVYG KQWRDWEDKN GNHYDQLKSV IQQIKTNPNS
RRHIVSAWNP TEIDSMALPP CHTMFQFYVQ EGKLNCQLYQ RSADIFLGVP FNIASYALLT
HLVAKECGLE VGEFIHTFGD AHIYSNHMDA IHTQLSRDSY LPPQLKINTD KSIFDINYED
LELINYESHP AIKAPIAV
