ID   TYSY_MANSM              Reviewed;         283 AA.
AC   Q65VJ8;
DT   26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2004, sequence version 1.
DT   03-AUG-2022, entry version 95.
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=MS0405;
OS   Mannheimia succiniciproducens (strain MBEL55E).
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC   Pasteurellaceae; Basfia.
OX   NCBI_TaxID=221988;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=MBEL55E;
RX   PubMed=15378067; DOI=10.1038/nbt1010;
RA   Hong S.H., Kim J.S., Lee S.Y., In Y.H., Choi S.S., Rih J.-K., Kim C.H.,
RA   Jeong H., Hur C.G., Kim J.J.;
RT   "The genome sequence of the capnophilic rumen bacterium Mannheimia
RT   succiniciproducens.";
RL   Nat. Biotechnol. 22:1275-1281(2004).
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; AE016827; AAU37012.1; -; Genomic_DNA.
DR   RefSeq; WP_011199587.1; NC_006300.1.
DR   AlphaFoldDB; Q65VJ8; -.
DR   SMR; Q65VJ8; -.
DR   STRING; 221988.MS0405; -.
DR   EnsemblBacteria; AAU37012; AAU37012; MS0405.
DR   KEGG; msu:MS0405; -.
DR   eggNOG; COG0207; Bacteria.
DR   HOGENOM; CLU_021669_0_1_6; -.
DR   OMA; KQYLDLC; -.
DR   OrthoDB; 1212177at2; -.
DR   UniPathway; UPA00575; -.
DR   Proteomes; UP000000607; 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; -; 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   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.
PE   3: Inferred from homology;
KW   Cytoplasm; Methyltransferase; Nucleotide biosynthesis; Transferase.
FT   CHAIN           1..283
FT                   /note="Thymidylate synthase"
FT                   /id="PRO_0000140978"
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;  32687 MW;  ED695E7F6DDD865B CRC64;
     MRQYLDLCQR IVNEGCWIEN KRTGKRCLTV INADLTYDVA NNRFPIITTR KSYWKAAIAE
     FLGYIRGYDN AADFRKLGAK TWDANANENQ VWLNNPHRKG TDDMGRVYGV QGRAWRKPNG
     ETVDQLRKIV NNLSRGIDDR GEILTFLNPG EFDLGCLRPC MYNHTFSLLG DTLYLTSYQR
     SCDVPLGLNF NQIQVFTFLA LMAQITGKKA GQAYHKIVNA HIYEDQLELM RDVQLKREPF
     PSPKLEINPD IKTLEDLETW VTMDDFNVVG YQCHEPIKYP FSV