ID   TYSY_XENNA              Reviewed;         264 AA.
AC   Q6REU8; D3VCN8;
DT   26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   27-MAR-2024, entry version 100.
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=XNC1_4048;
OS   Xenorhabdus nematophila (strain ATCC 19061 / DSM 3370 / CCUG 14189 / LMG
OS   1036 / NCIMB 9965 / AN6).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC   Morganellaceae; Xenorhabdus.
OX   NCBI_TaxID=406817;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 19061 / DSM 3370 / CCUG 14189 / LMG 1036 / NCIMB 9965 /
RC   AN6;
RA   Orchard S.S., Goodrich-Blair H.;
RT   "Characterization of dTMP synthesis in Xenorhabdus nematophila and
RT   evaluation of dT availability in the insect and nematode hosts.";
RL   Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 19061 / DSM 3370 / CCUG 14189 / LMG 1036 / NCIMB 9965 /
RC   AN6;
RX   PubMed=22125637; DOI=10.1371/journal.pone.0027909;
RA   Chaston J.M., Suen G., Tucker S.L., Andersen A.W., Bhasin A., Bode E.,
RA   Bode H.B., Brachmann A.O., Cowles C.E., Cowles K.N., Darby C., de Leon L.,
RA   Drace K., Du Z., Givaudan A., Herbert Tran E.E., Jewell K.A., Knack J.J.,
RA   Krasomil-Osterfeld K.C., Kukor R., Lanois A., Latreille P.,
RA   Leimgruber N.K., Lipke C.M., Liu R., Lu X., Martens E.C., Marri P.R.,
RA   Medigue C., Menard M.L., Miller N.M., Morales-Soto N., Norton S.,
RA   Ogier J.C., Orchard S.S., Park D., Park Y., Qurollo B.A., Sugar D.R.,
RA   Richards G.R., Rouy Z., Slominski B., Slominski K., Snyder H., Tjaden B.C.,
RA   van der Hoeven R., Welch R.D., Wheeler C., Xiang B., Barbazuk B.,
RA   Gaudriault S., Goodner B., Slater S.C., Forst S., Goldman B.S.,
RA   Goodrich-Blair H.;
RT   "The entomopathogenic bacterial endosymbionts xenorhabdus and photorhabdus:
RT   convergent lifestyles from divergent genomes.";
RL   PLoS ONE 6:E27909-E27909(2011).
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; AY502024; AAS80323.1; -; Genomic_DNA.
DR   EMBL; FN667742; CBJ92073.1; -; Genomic_DNA.
DR   RefSeq; WP_013185453.1; NC_014228.1.
DR   AlphaFoldDB; Q6REU8; -.
DR   SMR; Q6REU8; -.
DR   STRING; 406817.XNC1_4048; -.
DR   KEGG; xne:XNC1_4048; -.
DR   eggNOG; COG0207; Bacteria.
DR   HOGENOM; CLU_021669_0_0_6; -.
DR   UniPathway; UPA00575; -.
DR   Proteomes; UP000008075; 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; 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; 2.
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..264
FT                   /note="Thymidylate synthase"
FT                   /id="PRO_0000141048"
FT   ACT_SITE        146
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT   BINDING         21
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         51
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         126..127
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         166..169
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         169
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         177
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         207..209
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         263
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   264 AA;  30352 MW;  2A7C5C0336794B07 CRC64;
     MKQYLDLMKK VLEEGTAKDD RTGTGTRSIF GHQMRFNLQE GFPLVTTKRC HLRSIIHELL
     WFLNGDTNIK YLHDNGVSIW DEWADENGDL GPVYGKQWRA WGSADGRHID QLTQVLEQLK
     GDPDSRRIIV SAWNVGELDK MALAPCHAFF QFYVADGKLS CQLYQRSCDV FLGLPFNIAS
     YALLVHMMAQ QCNLDVGDFV WTGGDTHLYN NHLEQTHLQL SREPRALPKL VIKRKPDSLF
     DYRFEDFEIV DYDPYPGIKA PVAI
//