ID TYSY_ECOLI Reviewed; 264 AA. AC P0A884; P00470; Q2MA10; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 27-MAR-2024, entry version 148. DE RecName: Full=Thymidylate synthase {ECO:0000255|HAMAP-Rule:MF_00008, ECO:0000303|PubMed:2223754, ECO:0000303|PubMed:3286637, ECO:0000303|PubMed:6308660}; DE Short=TS {ECO:0000255|HAMAP-Rule:MF_00008, ECO:0000303|PubMed:2223754, ECO:0000303|PubMed:3286637, ECO:0000303|PubMed:7708505}; DE Short=TSase {ECO:0000255|HAMAP-Rule:MF_00008}; DE EC=2.1.1.45 {ECO:0000255|HAMAP-Rule:MF_00008, ECO:0000269|PubMed:2223754, ECO:0000269|PubMed:3286637, ECO:0000269|PubMed:9826509}; GN Name=thyA {ECO:0000255|HAMAP-Rule:MF_00008, GN ECO:0000303|PubMed:6308660}; OrderedLocusNames=b2827, JW2795; OS Escherichia coli (strain K12). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Enterobacteriaceae; Escherichia. OX NCBI_TaxID=83333; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE. RC STRAIN=K12 / JM103 / ATCC 39403 / DSM 2829 / KCTC 1112 / NCIMB 12044; RX PubMed=6308660; DOI=10.1073/pnas.80.16.4914; RA Belfort M., Maley G.F., Pedersen-Lane J., Maley F.; RT "Primary structure of the Escherichia coli thyA gene and its thymidylate RT synthase product."; RL Proc. Natl. Acad. Sci. U.S.A. 80:4914-4918(1983). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / MG1655 / ATCC 47076; RX PubMed=9278503; DOI=10.1126/science.277.5331.1453; RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., RA Shao Y.; RT "The complete genome sequence of Escherichia coli K-12."; RL Science 277:1453-1462(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RX PubMed=16738553; DOI=10.1038/msb4100049; RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.; RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 RT and W3110."; RL Mol. Syst. Biol. 2:E1-E5(2006). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 63-264. RX PubMed=3520484; DOI=10.1093/nar/14.11.4437; RA Finch P.W., Wilson R.E., Brown K., Hickson I.D., Tomkinson A.E., RA Emmerson P.T.; RT "Complete nucleotide sequence of the Escherichia coli recC gene and of the RT thyA-recC intergenic region."; RL Nucleic Acids Res. 14:4437-4451(1986). RN [5] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF CYS-50. RX PubMed=3286637; DOI=10.1016/s0021-9258(18)68543-6; RA Maley G.F., Maley F.; RT "Properties of a defined mutant of Escherichia coli thymidylate synthase."; RL J. Biol. Chem. 263:7620-7627(1988). RN [6] RP MUTAGENESIS. RX PubMed=1518803; DOI=10.1002/prot.340130407; RA Kim C.W., Michaels M.L., Miller J.F.; RT "Amino acid substitution analysis of E. coli thymidylate synthase: the RT study of a highly conserved region at the N-terminus."; RL Proteins 13:352-363(1992). RN [7] RP FUNCTION, AND MECHANISM OF TRANSLATION REGULATION. RX PubMed=7708505; DOI=10.1093/nar/23.5.869; RA Voeller D.M., Changchien L.-M., Maley G.F., Maley F., Takechi T., RA Turner R.E., Montfort W.R., Allegra C.J., Chu E.; RT "Characterization of a specific interaction between Escherichia coli RT thymidylate synthase and Escherichia coli thymidylate synthase mRNA."; RL Nucleic Acids Res. 23:869-875(1995). RN [8] RP IDENTIFICATION BY 2D-GEL. RX PubMed=9298644; DOI=10.1002/elps.1150180805; RA VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.; RT "Escherichia coli proteome analysis using the gene-protein database."; RL Electrophoresis 18:1243-1251(1997). RN [9] RP X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS) IN COMPLEX WITH DUMP, FUNCTION, RP CATALYTIC ACTIVITY, ACTIVE SITE, AND SUBUNIT. RX PubMed=2223754; DOI=10.1021/bi00482a004; RA Montfort W.R., Perry K.M., Fauman E.B., Finer-Moore J.S., Maley G.F., RA Hardy L., Maley F., Stroud R.M.; RT "Structure, multiple site binding, and segmental accommodation in RT thymidylate synthase on binding dUMP and an anti-folate."; RL Biochemistry 29:6964-6977(1990). RN [10] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS). RX PubMed=2128651; DOI=10.1002/prot.340080406; RA Perry K.M., Fauman E.B., Finer-Moore J.S., Montfort W.R., Maley G.F., RA Maley F., Stroud R.M.; RT "Plastic adaptation toward mutations in proteins: structural comparison of RT thymidylate synthases."; RL Proteins 8:315-333(1990). RN [11] RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) IN COMPLEX WITH DIHYDROFOLATE AND RP TMP. RX PubMed=8312270; DOI=10.1021/bi00172a029; RA Fauman E.B., Rutenber E.E., Maley G.F., Maley F., Stroud R.M.; RT "Water-mediated substrate/product discrimination: the product complex of RT thymidylate synthase at 1.83 A."; RL Biochemistry 33:1502-1511(1994). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF MUTANT GLN-58 IN COMPLEX WITH RP DUMP, ACTIVE SITE, AND SUBUNIT. RX PubMed=8973201; DOI=10.1021/bi961269r; RA Sage C.R., Rutenber E.E., Stout T.J., Stroud R.M.; RT "An essential role for water in an enzyme reaction mechanism: the crystal RT structure of the thymidylate synthase mutant E58Q."; RL Biochemistry 35:16270-16281(1996). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF MUTANT GLU-126 IN COMPLEX WITH RP DUMP, MUTAGENESIS OF ARG-126, REACTION MECHANISM, AND ACTIVE SITE. RX PubMed=9416600; DOI=10.1002/pro.5560061203; RA Strop P., Changchien L., Maley F., Montfort W.R.; RT "Crystal structures of a marginally active thymidylate synthase mutant, Arg RT 126-->Glu."; RL Protein Sci. 6:2504-2511(1997). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT ALA-177 IN COMPLEX WITH RP DUMP, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF ASN-177. RX PubMed=9826509; DOI=10.1006/jmbi.1998.2205; RA Reyes C.L., Sage C.R., Rutenber E.E., Nissen R.M., Finer-Moore J.S., RA Stroud R.M.; RT "Inactivity of N229A thymidylate synthase due to water-mediated effects: RT isolating a late stage in methyl transfer."; RL J. Mol. Biol. 284:699-712(1998). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS). RX PubMed=10944209; DOI=10.1073/pnas.97.17.9367; RA Erlanson D.A., Braisted A.C., Raphael D.R., Randal M., Stroud R.M., RA Gordon E.M., Wells J.A.; RT "Site-directed ligand discovery."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9367-9372(2000). 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-product CC (PubMed:3286637, PubMed:2223754, PubMed:9826509). This enzymatic CC reaction provides an intracellular de novo source of dTMP, an essential CC precursor for DNA biosynthesis. This protein also binds to its mRNA CC thus repressing its own translation (PubMed:7708505). CC {ECO:0000269|PubMed:2223754, ECO:0000269|PubMed:3286637, CC ECO:0000269|PubMed:7708505, ECO:0000269|PubMed:9826509}. 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 ECO:0000269|PubMed:2223754, ECO:0000269|PubMed:3286637, CC ECO:0000269|PubMed:9826509}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=50 uM for dUMP {ECO:0000269|PubMed:3286637}; CC KM=25 uM for 5,10-methylenetetrahydrofolate CC {ECO:0000269|PubMed:3286637}; CC KM=4.1 uM for dUMP {ECO:0000269|PubMed:9826509}; CC KM=13.6 uM for 5,10-methylenetetrahydrofolate CC {ECO:0000269|PubMed:9826509}; CC Vmax=5.47 umol/min/mg enzyme {ECO:0000269|PubMed:3286637}; CC Note=kcat is 8.8 sec(-1). {ECO:0000269|PubMed:9826509}; CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis. {ECO:0000255|HAMAP- CC Rule:MF_00008}. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:2223754, CC ECO:0000269|PubMed:8973201}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00008}. CC -!- PTM: Although not discussed in the published references, Met-1 is CC represented in the submitted PDB entries as being modified by either a CC formyl, or a carboxyl group. The N-terminal is probably N- CC (dihydroxymethyl)methionine, the hydrated form of N-formylmethionine. CC -!- SIMILARITY: Belongs to the thymidylate synthase family. Bacterial-type CC ThyA subfamily. {ECO:0000255|HAMAP-Rule:MF_00008}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J01710; AAA24675.1; -; Genomic_DNA. DR EMBL; U29581; AAB40474.1; -; Genomic_DNA. DR EMBL; U00096; AAC75866.1; -; Genomic_DNA. DR EMBL; AP009048; BAE76896.1; -; Genomic_DNA. DR EMBL; X03966; CAA27600.1; -; Genomic_DNA. DR PIR; A00549; SYECT. DR RefSeq; NP_417304.1; NC_000913.3. DR RefSeq; WP_000816232.1; NZ_STEB01000034.1. DR PDB; 1AIQ; X-ray; 2.20 A; A/B=1-264. DR PDB; 1AJM; X-ray; 2.40 A; A=1-264. DR PDB; 1AN5; X-ray; 2.60 A; A/B=1-264. DR PDB; 1AOB; X-ray; 2.10 A; A=1-264. DR PDB; 1AXW; X-ray; 1.70 A; A/B=1-264. DR PDB; 1BDU; X-ray; 2.10 A; A=1-264. DR PDB; 1BID; X-ray; 2.20 A; A=1-264. DR PDB; 1BJG; X-ray; 2.30 A; A=1-264. DR PDB; 1BQ1; X-ray; 2.50 A; A/B=1-264. DR PDB; 1BQ2; X-ray; 2.20 A; A=1-264. DR PDB; 1DDU; X-ray; 2.10 A; A/B=1-264. DR PDB; 1DNA; X-ray; 2.20 A; A/B=1-264. DR PDB; 1EV5; X-ray; 1.70 A; A=1-264. DR PDB; 1EV8; X-ray; 2.60 A; A=1-264. DR PDB; 1EVF; X-ray; 1.70 A; A=1-264. DR PDB; 1EVG; X-ray; 2.00 A; A=1-264. DR PDB; 1F4B; X-ray; 1.75 A; A=1-264. DR PDB; 1F4C; X-ray; 2.00 A; A/B=1-264. DR PDB; 1F4D; X-ray; 2.15 A; A/B=1-264. DR PDB; 1F4E; X-ray; 1.90 A; A=1-264. DR PDB; 1F4F; X-ray; 2.00 A; A/B=1-264. DR PDB; 1F4G; X-ray; 1.75 A; A/B=1-264. DR PDB; 1FFL; X-ray; 2.94 A; A=1-264. DR PDB; 1FWM; X-ray; 2.20 A; A/B=1-264. DR PDB; 1JG0; X-ray; 2.00 A; A/B=1-264. DR PDB; 1JTQ; X-ray; 2.50 A; A/B=1-264. DR PDB; 1JTU; X-ray; 2.20 A; A/B=1-264. DR PDB; 1JUT; X-ray; 2.70 A; A/B=1-264. DR PDB; 1KCE; X-ray; 2.00 A; A/B=1-264. DR PDB; 1KZI; X-ray; 1.75 A; A/B=1-264. DR PDB; 1KZJ; X-ray; 2.60 A; A/B/C/D/E/F=1-264. DR PDB; 1NCE; X-ray; 2.40 A; A/B=1-264. DR PDB; 1QQQ; X-ray; 1.50 A; A=1-264. DR PDB; 1SYN; X-ray; 2.00 A; A/B=1-264. DR PDB; 1TDU; X-ray; 2.10 A; A/B=1-264. DR PDB; 1TJS; X-ray; 2.20 A; A=1-264. DR PDB; 1TLC; X-ray; 2.10 A; A/B=1-264. DR PDB; 1TLS; X-ray; 2.60 A; A/B=1-264. DR PDB; 1TRG; X-ray; 1.90 A; A=1-264. DR PDB; 1TSD; X-ray; 1.95 A; A/B=1-264. DR PDB; 1TSN; X-ray; 2.20 A; A=1-264. DR PDB; 1TYS; X-ray; 1.80 A; A=1-264. DR PDB; 1ZPR; X-ray; 2.50 A; A/B=1-264. DR PDB; 2A9W; X-ray; 1.65 A; A/B/C/D=1-264. DR PDB; 2BBQ; X-ray; 2.30 A; A/B=1-264. DR PDB; 2FTN; X-ray; 1.60 A; A=1-264. DR PDB; 2FTO; X-ray; 2.00 A; X=1-264. DR PDB; 2FTQ; X-ray; 1.81 A; A=1-264. DR PDB; 2G8X; X-ray; 1.83 A; A/B=1-264. DR PDB; 2KCE; X-ray; 2.20 A; A/B=1-264. DR PDB; 2TSC; X-ray; 1.97 A; A/B=1-264. DR PDB; 2VET; X-ray; 2.20 A; A=1-264. DR PDB; 2VF0; X-ray; 3.00 A; A/B=1-264. DR PDB; 3B5B; X-ray; 2.70 A; A/B=1-264. DR PDB; 3B9H; X-ray; 2.49 A; A=1-264. DR PDB; 3BFI; X-ray; 2.20 A; A=1-264. DR PDB; 3BGX; X-ray; 1.93 A; A=1-264. DR PDB; 3BHL; X-ray; 1.40 A; A/B=1-264. DR PDB; 3BHR; X-ray; 1.90 A; A=1-264. DR PDB; 3TMS; X-ray; 2.10 A; A=1-264. DR PDB; 4F2V; X-ray; 2.49 A; A/B=1-264. DR PDB; 4GEV; X-ray; 1.30 A; A/B=1-264. DR PDB; 4ISK; X-ray; 1.75 A; A/B/C/D/E/F/G/H=2-264. DR PDB; 6CDZ; X-ray; 2.40 A; A/B=1-263. DR PDB; 6NNR; X-ray; 1.05 A; A/B=1-264. DR PDB; 7JX1; X-ray; 1.82 A; A/B=1-264. DR PDB; 7JXF; X-ray; 1.50 A; A/B=1-264. DR PDBsum; 1AIQ; -. DR PDBsum; 1AJM; -. DR PDBsum; 1AN5; -. DR PDBsum; 1AOB; -. DR PDBsum; 1AXW; -. DR PDBsum; 1BDU; -. DR PDBsum; 1BID; -. DR PDBsum; 1BJG; -. DR PDBsum; 1BQ1; -. DR PDBsum; 1BQ2; -. DR PDBsum; 1DDU; -. DR PDBsum; 1DNA; -. DR PDBsum; 1EV5; -. DR PDBsum; 1EV8; -. DR PDBsum; 1EVF; -. DR PDBsum; 1EVG; -. DR PDBsum; 1F4B; -. DR PDBsum; 1F4C; -. DR PDBsum; 1F4D; -. DR PDBsum; 1F4E; -. DR PDBsum; 1F4F; -. DR PDBsum; 1F4G; -. DR PDBsum; 1FFL; -. DR PDBsum; 1FWM; -. DR PDBsum; 1JG0; -. DR PDBsum; 1JTQ; -. DR PDBsum; 1JTU; -. DR PDBsum; 1JUT; -. DR PDBsum; 1KCE; -. DR PDBsum; 1KZI; -. DR PDBsum; 1KZJ; -. DR PDBsum; 1NCE; -. DR PDBsum; 1QQQ; -. DR PDBsum; 1SYN; -. DR PDBsum; 1TDU; -. DR PDBsum; 1TJS; -. DR PDBsum; 1TLC; -. DR PDBsum; 1TLS; -. DR PDBsum; 1TRG; -. DR PDBsum; 1TSD; -. DR PDBsum; 1TSN; -. DR PDBsum; 1TYS; -. DR PDBsum; 1ZPR; -. DR PDBsum; 2A9W; -. DR PDBsum; 2BBQ; -. DR PDBsum; 2FTN; -. DR PDBsum; 2FTO; -. DR PDBsum; 2FTQ; -. DR PDBsum; 2G8X; -. DR PDBsum; 2KCE; -. DR PDBsum; 2TSC; -. DR PDBsum; 2VET; -. DR PDBsum; 2VF0; -. DR PDBsum; 3B5B; -. DR PDBsum; 3B9H; -. DR PDBsum; 3BFI; -. DR PDBsum; 3BGX; -. DR PDBsum; 3BHL; -. DR PDBsum; 3BHR; -. DR PDBsum; 3TMS; -. DR PDBsum; 4F2V; -. DR PDBsum; 4GEV; -. DR PDBsum; 4ISK; -. DR PDBsum; 6CDZ; -. DR PDBsum; 6NNR; -. DR PDBsum; 7JX1; -. DR PDBsum; 7JXF; -. DR AlphaFoldDB; P0A884; -. DR SMR; P0A884; -. DR BioGRID; 4262058; 217. DR DIP; DIP-48261N; -. DR IntAct; P0A884; 5. DR STRING; 511145.b2827; -. DR BindingDB; P0A884; -. DR ChEMBL; CHEMBL2555; -. DR DrugBank; DB02031; (6S)-5,6,7,8-tetrahydrofolic acid. DR DrugBank; DB04447; 1,4-Dithiothreitol. DR DrugBank; DB03541; 10-Propargyl-5,8-Dideazafolic Acid. DR DrugBank; DB03274; 2',5'-Dideoxyuridine. DR DrugBank; DB04457; 2'-Deoxyguanosine-5'-Monophosphate. DR DrugBank; DB02256; 2'-Deoxyuridine. DR DrugBank; DB08131; 2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-3-METHYL-BUTYRIC ACID. DR DrugBank; DB04696; 4-CHLORO-3',3''-DIBROMOPHENOL-1,8-NAPHTHALEIN. DR DrugBank; DB02301; 5,10-Methylene-6-Hydrofolic Acid. DR DrugBank; DB03761; 5-fluoro-2'-deoxyuridine-5'-monophosphate. DR DrugBank; DB03800; Deoxyuridine monophosphate. DR DrugBank; DB02467; L-methionine (S)-S-oxide. DR DrugBank; DB02223; LY231514 tetra glu. DR DrugBank; DB03038; LY341770. DR DrugBank; DB03157; N,O-didansyl-L-tyrosine. DR DrugBank; DB03818; N-[Tosyl-D-Prolinyl]Amino-Ethanethiol. DR DrugBank; DB02899; N-Carboxymethionine. DR DrugBank; DB04586; o-Bromophenol. DR DrugBank; DB04530; S,S-(2-Hydroxyethyl)Thiocysteine. DR DrugBank; DB04503; Sp-722. DR DrugBank; DB03558; SP-876. DR DrugBank; DB02752; Tosyl-D-Proline. DR DrugCentral; P0A884; -. DR jPOST; P0A884; -. DR PaxDb; 511145-b2827; -. DR EnsemblBacteria; AAC75866; AAC75866; b2827. DR GeneID; 83579666; -. DR GeneID; 949035; -. DR KEGG; ecj:JW2795; -. DR KEGG; eco:b2827; -. DR PATRIC; fig|1411691.4.peg.3908; -. DR EchoBASE; EB0995; -. DR eggNOG; COG0207; Bacteria. DR HOGENOM; CLU_021669_0_0_6; -. DR InParanoid; P0A884; -. DR OMA; IVYELLW; -. DR OrthoDB; 9774633at2; -. DR PhylomeDB; P0A884; -. DR BioCyc; EcoCyc:THYMIDYLATESYN-MONOMER; -. DR BioCyc; MetaCyc:THYMIDYLATESYN-MONOMER; -. DR BRENDA; 2.1.1.45; 2026. DR SABIO-RK; P0A884; -. DR UniPathway; UPA00575; -. DR EvolutionaryTrace; P0A884; -. DR PRO; PR:P0A884; -. DR Proteomes; UP000000318; Chromosome. DR Proteomes; UP000000625; Chromosome. DR GO; GO:0005829; C:cytosol; IDA:EcoCyc. DR GO; GO:0000287; F:magnesium ion binding; IDA:EcoCyc. DR GO; GO:0042803; F:protein homodimerization activity; IDA:EcoCyc. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0004799; F:thymidylate synthase activity; IDA:EcoCyc. DR GO; GO:0006231; P:dTMP biosynthetic process; IDA:EcoCyc. DR GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW. DR GO; GO:0009314; P:response to radiation; IMP:EcoCyc. 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 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Direct protein sequencing; Formylation; KW Methyltransferase; Nucleotide biosynthesis; Reference proteome; Repressor; KW RNA-binding; Transferase; Translation regulation. FT CHAIN 1..264 FT /note="Thymidylate synthase" FT /id="PRO_0000140954" FT ACT_SITE 146 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008, FT ECO:0000269|PubMed:2223754, ECO:0000269|PubMed:8973201, FT ECO:0000269|PubMed:9416600" 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:0000269|PubMed:2223754, FT ECO:0000269|PubMed:8973201, ECO:0007744|PDB:1KCE, FT ECO:0007744|PDB:2TSC" FT BINDING 51 FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:15636" FT /evidence="ECO:0000305|PubMed:8312270, FT ECO:0007744|PDB:1TYS" FT BINDING 126..127 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000269|PubMed:2223754, FT ECO:0000269|PubMed:8973201, ECO:0007744|PDB:1KCE, FT ECO:0007744|PDB:2TSC" 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:0000269|PubMed:2223754, FT ECO:0000269|PubMed:8973201, ECO:0007744|PDB:1KCE, FT ECO:0007744|PDB:2TSC" FT BINDING 169 FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:15636" FT /evidence="ECO:0000305|PubMed:8312270, FT ECO:0007744|PDB:1TYS" 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:0000269|PubMed:2223754, FT ECO:0000269|PubMed:8973201, ECO:0007744|PDB:1KCE, FT ECO:0007744|PDB:2TSC" 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:0000269|PubMed:2223754, FT ECO:0000269|PubMed:8973201, ECO:0007744|PDB:1KCE, FT ECO:0007744|PDB:2TSC" FT BINDING 263 FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:15636" FT /evidence="ECO:0000305|PubMed:8312270, FT ECO:0007744|PDB:1TYS" FT MUTAGEN 50 FT /note="C->Y: Shows 0.2% of wild-type catalytic activity, FT but substrate affinity is not affected." FT /evidence="ECO:0000269|PubMed:3286637" FT MUTAGEN 126 FT /note="R->E: Shows 2000-fold decrease in catalytic activity FT and 600-fold decrease in affinity for dUMP." FT /evidence="ECO:0000269|PubMed:9416600" FT MUTAGEN 177 FT /note="N->A: Shows 200-fold decrease in catalytic activity, FT 20-fold decrease in affinity for dUMP, and 10-fold decrease FT in affinity for mTHF." FT /evidence="ECO:0000269|PubMed:9826509" FT HELIX 2..14 FT /evidence="ECO:0007829|PDB:6NNR" FT STRAND 16..18 FT /evidence="ECO:0007829|PDB:6NNR" FT STRAND 21..23 FT /evidence="ECO:0007829|PDB:2G8X" FT STRAND 26..37 FT /evidence="ECO:0007829|PDB:6NNR" FT HELIX 38..40 FT /evidence="ECO:0007829|PDB:6NNR" FT STRAND 46..48 FT /evidence="ECO:0007829|PDB:2A9W" FT HELIX 52..64 FT /evidence="ECO:0007829|PDB:6NNR" FT HELIX 70..74 FT /evidence="ECO:0007829|PDB:6NNR" FT HELIX 81..83 FT /evidence="ECO:0007829|PDB:6NNR" FT HELIX 94..100 FT /evidence="ECO:0007829|PDB:6NNR" FT STRAND 101..103 FT /evidence="ECO:0007829|PDB:1JG0" FT TURN 104..106 FT /evidence="ECO:0007829|PDB:1JG0" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:1JG0" FT HELIX 111..121 FT /evidence="ECO:0007829|PDB:6NNR" FT STRAND 129..131 FT /evidence="ECO:0007829|PDB:6NNR" FT HELIX 135..140 FT /evidence="ECO:0007829|PDB:6NNR" FT STRAND 141..143 FT /evidence="ECO:0007829|PDB:6NNR" FT STRAND 146..155 FT /evidence="ECO:0007829|PDB:6NNR" FT STRAND 158..169 FT /evidence="ECO:0007829|PDB:6NNR" FT TURN 170..172 FT /evidence="ECO:0007829|PDB:6NNR" FT HELIX 173..192 FT /evidence="ECO:0007829|PDB:6NNR" FT STRAND 195..209 FT /evidence="ECO:0007829|PDB:6NNR" FT HELIX 210..212 FT /evidence="ECO:0007829|PDB:6NNR" FT HELIX 213..220 FT /evidence="ECO:0007829|PDB:6NNR" FT STRAND 229..232 FT /evidence="ECO:0007829|PDB:6NNR" FT HELIX 239..241 FT /evidence="ECO:0007829|PDB:1AXW" FT HELIX 244..246 FT /evidence="ECO:0007829|PDB:6NNR" FT STRAND 247..251 FT /evidence="ECO:0007829|PDB:6NNR" SQ SEQUENCE 264 AA; 30480 MW; 0E6D88ED98D24D22 CRC64; MKQYLELMQK VLDEGTQKND RTGTGTLSIF GHQMRFNLQD GFPLVTTKRC HLRSIIHELL WFLQGDTNIA YLHENNVTIW DEWADENGDL GPVYGKQWRA WPTPDGRHID QITTVLNQLK NDPDSRRIIV SAWNVGELDK MALAPCHAFF QFYVADGKLS CQLYQRSCDV FLGLPFNIAS YALLVHMMAQ QCDLEVGDFV WTGGDTHLYS NHMDQTHLQL SREPRPLPKL IIKRKPESIF DYRFEDFEIE GYDPHPGIKA PVAI //