TYSY_METFK
ID TYSY_METFK Reviewed; 264 AA.
AC Q9RAM7; Q1H2G9;
DT 25-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 2.
DT 03-AUG-2022, 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=thyA1 {ECO:0000255|HAMAP-Rule:MF_00008}; OrderedLocusNames=Mfla_0906;
GN and
GN Name=thyA2 {ECO:0000255|HAMAP-Rule:MF_00008}; OrderedLocusNames=Mfla_1050;
OS Methylobacillus flagellatus (strain KT / ATCC 51484 / DSM 6875).
OC Bacteria; Proteobacteria; Betaproteobacteria; Nitrosomonadales;
OC Methylophilaceae; Methylobacillus.
OX NCBI_TaxID=265072;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10589737; DOI=10.1099/00221287-145-11-3273;
RA Marchenko G.N., Marchenko N.D., Tsygankov Y.D., Chistoserdov A.Y.;
RT "Organization of threonine biosynthesis genes from the obligate
RT methylotroph Methylobacillus flagellatus.";
RL Microbiology 145:3273-3282(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=KT / ATCC 51484 / DSM 6875;
RG US DOE Joint Genome Institute;
RA Copeland A., Lucas S., Lapidus A., Barry K., Detter J.C.,
RA Glavina del Rio T., Hammon N., Israni S., Dalin E., Tice H., Pitluck S.,
RA Brettin T., Bruce D., Han C., Tapia R., Saunders E., Gilna P., Schmutz J.,
RA Larimer F., Land M., Kyrpides N., Anderson I., Richardson P.;
RT "Complete sequence of Methylobacillus flagellatus KT.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
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; L78665; AAF21131.1; -; Genomic_DNA.
DR EMBL; CP000284; ABE49318.1; -; Genomic_DNA.
DR EMBL; CP000284; ABE49174.1; -; Genomic_DNA.
DR RefSeq; WP_011479271.1; NC_007947.1.
DR AlphaFoldDB; Q9RAM7; -.
DR SMR; Q9RAM7; -.
DR STRING; 265072.Mfla_0906; -.
DR EnsemblBacteria; ABE49174; ABE49174; Mfla_0906.
DR EnsemblBacteria; ABE49318; ABE49318; Mfla_1050.
DR KEGG; mfa:Mfla_0906; -.
DR KEGG; mfa:Mfla_1050; -.
DR eggNOG; COG0207; Bacteria.
DR HOGENOM; CLU_021669_0_0_4; -.
DR OMA; KQYLDLC; -.
DR OrthoDB; 1212177at2; -.
DR UniPathway; UPA00575; -.
DR Proteomes; UP000002440; 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 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; 2.
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_0000140981"
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"
FT CONFLICT 53..54
FT /note="KS -> NA (in Ref. 1; AAF21131)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="R -> S (in Ref. 1; AAF21131)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="K -> E (in Ref. 1; AAF21131)"
FT /evidence="ECO:0000305"
FT CONFLICT 149
FT /note="F -> L (in Ref. 1; AAF21131)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="D -> E (in Ref. 1; AAF21131)"
FT /evidence="ECO:0000305"
FT CONFLICT 190
FT /note="Q -> R (in Ref. 1; AAF21131)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="K -> E (in Ref. 1; AAF21131)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 264 AA; 30282 MW; B2FF060956C70D40 CRC64;
MKVYHDLMRH VLEQGHKKED RTGTGTLSVF GYQMRFDLSE GFPLLTTKKV HLKSIIHELL
WFLQGSTNIA YLKENGVTIW DEWADAEGNL GPVYGYQWRN WPKPDGGHID QISEVIAAIK
RNPDSRRLIV SAWNVADVDK MKLPPCHAFF QFYVADGKLS CQLYQRSADI FLGVPFNIAS
YALLTMMVAQ VCDLKLGDFV HTLGDAHIYL NHLEQVKEQL SREPYPLPVM RINPEVKDIF
AFRFEDFTLE NYQSHPAIKA PVAV
