TYSY_LACLA
ID TYSY_LACLA Reviewed; 279 AA.
AC P19368; Q9CFD8;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 2.
DT 03-AUG-2022, entry version 130.
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=LL1541;
GN ORFNames=L182559;
OS Lactococcus lactis subsp. lactis (strain IL1403) (Streptococcus lactis).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Lactococcus.
OX NCBI_TaxID=272623;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=712;
RX PubMed=2117882; DOI=10.1128/aem.56.7.2156-2163.1990;
RA Ross P., O'Gara F., Condon S.;
RT "Cloning and characterization of the thymidylate synthase gene from
RT Lactococcus lactis subsp. lactis.";
RL Appl. Environ. Microbiol. 56:2156-2163(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=IL1403;
RX PubMed=11337471; DOI=10.1101/gr.gr-1697r;
RA Bolotin A., Wincker P., Mauger S., Jaillon O., Malarme K., Weissenbach J.,
RA Ehrlich S.D., Sorokin A.;
RT "The complete genome sequence of the lactic acid bacterium Lactococcus
RT lactis ssp. lactis IL1403.";
RL Genome Res. 11:731-753(2001).
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; M33770; AAA25221.1; -; Genomic_DNA.
DR EMBL; AE005176; AAK05639.1; -; Genomic_DNA.
DR PIR; A43797; A43797.
DR PIR; E86817; E86817.
DR RefSeq; NP_267697.1; NC_002662.1.
DR RefSeq; WP_003130015.1; NC_002662.1.
DR AlphaFoldDB; P19368; -.
DR SMR; P19368; -.
DR STRING; 272623.L182559; -.
DR PaxDb; P19368; -.
DR EnsemblBacteria; AAK05639; AAK05639; L182559.
DR KEGG; lla:L182559; -.
DR PATRIC; fig|272623.7.peg.1652; -.
DR eggNOG; COG0207; Bacteria.
DR HOGENOM; CLU_021669_0_0_9; -.
DR OMA; WNEWEVG; -.
DR UniPathway; UPA00575; -.
DR Proteomes; UP000002196; 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 PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE 3: Inferred from homology;
KW Cytoplasm; Methyltransferase; Nucleotide biosynthesis; Reference proteome;
KW Transferase.
FT CHAIN 1..279
FT /note="Thymidylate synthase"
FT /id="PRO_0000140969"
FT ACT_SITE 153
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT BINDING 132..133
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 178..181
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
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 189
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 219..221
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 278
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 6..7
FT /note="KI -> QV (in Ref. 1; AAA25221)"
FT /evidence="ECO:0000305"
FT CONFLICT 34
FT /note="T -> M (in Ref. 1; AAA25221)"
FT /evidence="ECO:0000305"
FT CONFLICT 83..84
FT /note="AI -> SV (in Ref. 1; AAA25221)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="D -> E (in Ref. 1; AAA25221)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="Q -> K (in Ref. 1; AAA25221)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="V -> M (in Ref. 1; AAA25221)"
FT /evidence="ECO:0000305"
FT CONFLICT 238
FT /note="D -> E (in Ref. 1; AAA25221)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 279 AA; 32499 MW; CE0B97935D8DA1F8 CRC64;
MTYADKIFKQ NIQNILDNGV FSENARPKYK DGQTANSKYV TGSFVTYDLQ KGEFPITTLR
PIPIKSAIKE LMWIYQDQTS ELAILEEKYG VKYWGEWGIG DGTIGQRYGA TVKKYNIIGK
LLDGLAKNPW NRRNIINLWQ YEDFEETEGL LPCAFQTMFD VRREQDGQIY LDATLIQRSN
DMLVAHHINA MQYVALQMMI AKHFSWKVGK FFYFVNNLHI YDNQFEQANE LVKRTASDKE
PRLVLNVPDG TNFFDIKPED FELVDYEPVK PQLKFDLAI
