ID TYSY_BPT4 Reviewed; 286 AA. AC P00471; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 27-MAR-2024, entry version 131. DE RecName: Full=Thymidylate synthase; DE Short=TS; DE Short=TSase; DE EC=2.1.1.45; GN Name=TD; OS Enterobacteria phage T4 (Bacteriophage T4). OC Viruses; Duplodnaviria; Heunggongvirae; Uroviricota; Caudoviricetes; OC Straboviridae; Tevenvirinae; Tequatrovirus. OX NCBI_TaxID=10665; OH NCBI_TaxID=562; Escherichia coli. RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6328492; DOI=10.1073/pnas.81.10.3049; RA Chu F.K., Maley G.F., Maley F., Belfort M.; RT "Intervening sequence in the thymidylate synthase gene of bacteriophage RT T4."; RL Proc. Natl. Acad. Sci. U.S.A. 81:3049-3053(1984). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12626685; DOI=10.1128/mmbr.67.1.86-156.2003; RA Miller E.S., Kutter E., Mosig G., Arisaka F., Kunisawa T., Ruger W.; RT "Bacteriophage T4 genome."; RL Microbiol. Mol. Biol. Rev. 67:86-156(2003). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-42. RX PubMed=6327673; DOI=10.1016/s0021-9258(20)82135-8; RA Purohit S., Mathews C.K.; RT "Nucleotide sequence reveals overlap between T4 phage genes encoding RT dihydrofolate reductase and thymidylate synthase."; RL J. Biol. Chem. 259:6261-6266(1984). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 179-188. RX PubMed=3698096; DOI=10.1016/0092-8674(86)90379-x; RA Chu F.K., Maley G.F., West D.K., Belfort M., Maley F.; RT "Characterization of the intron in the phage T4 thymidylate synthase gene RT and evidence for its self-excision from the primary transcript."; RL Cell 45:157-166(1986). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 251-286. RX PubMed=2846540; DOI=10.1016/s0021-9258(18)37585-9; RA Tseng M.J., Hilfinger J.M., Walsh A., Greenberg G.R.; RT "Total sequence, flanking regions, and transcripts of bacteriophage T4 nrdA RT gene, coding for alpha chain of ribonucleoside diphosphate reductase."; RL J. Biol. Chem. 263:16242-16251(1988). RN [6] RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS). RX PubMed=7803410; DOI=10.1021/bi00255a028; RA Finer-Moore J.S., Maley G.F., Maley F., Montfort W.R., Stroud R.M.; RT "Crystal structure of thymidylate synthase from T4 phage: component of a RT deoxynucleoside triphosphate-synthesizing complex."; RL Biochemistry 33:15459-15468(1994). 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; CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis. CC -!- SUBUNIT: Homodimer. CC -!- MISCELLANEOUS: This enzyme is also expressed by the thyA gene of CC E.coli; the phage and host synthases exhibit striking dissimilarities CC in both structure and function. CC -!- SIMILARITY: Belongs to the thymidylate synthase family. {ECO:0000305}. 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; AH001329; AAA32492.1; -; Genomic_DNA. DR EMBL; AF158101; AAD42662.1; -; Genomic_DNA. DR EMBL; M12742; AAC12816.1; -; Genomic_DNA. DR EMBL; J03968; AAA32525.1; -; Genomic_DNA. DR PIR; A00550; SYBPT4. DR RefSeq; NP_049848.1; NC_000866.4. DR PDB; 1TIS; X-ray; 2.70 A; A=1-286. DR PDBsum; 1TIS; -. DR SMR; P00471; -. DR GeneID; 1258770; -. DR KEGG; vg:1258770; -. DR OrthoDB; 13491at10239; -. DR SABIO-RK; P00471; -. DR UniPathway; UPA00575; -. DR EvolutionaryTrace; P00471; -. DR Proteomes; UP000009087; Segment. DR GO; GO:0004799; F:thymidylate synthase activity; IMP:CACAO. DR GO; GO:0006231; P:dTMP biosynthetic process; IEA:InterPro. 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; 1. DR PANTHER; PTHR11548; THYMIDYLATE SYNTHASE 1; 1. DR PANTHER; PTHR11548:SF1; THYMIDYLATE SYNTHASE-RELATED; 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; Methyltransferase; Nucleotide biosynthesis; KW Reference proteome; Transferase. FT CHAIN 1..286 FT /note="Thymidylate synthase" FT /id="PRO_0000141061" FT ACT_SITE 156 FT /note="Nucleophile" FT /evidence="ECO:0000250|UniProtKB:P0A884" 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:0000250|UniProtKB:P0A884" FT BINDING 136..137 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT BINDING 176..179 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:0000250|UniProtKB:P0A884" FT BINDING 179 FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:15636" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT BINDING 187 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:0000250|UniProtKB:P0A884" FT BINDING 217..219 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:0000250|UniProtKB:P0A884" FT BINDING 285 FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:15636" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT HELIX 3..12 FT /evidence="ECO:0007829|PDB:1TIS" FT STRAND 26..30 FT /evidence="ECO:0007829|PDB:1TIS" FT STRAND 33..37 FT /evidence="ECO:0007829|PDB:1TIS" FT HELIX 38..40 FT /evidence="ECO:0007829|PDB:1TIS" FT HELIX 53..63 FT /evidence="ECO:0007829|PDB:1TIS" FT HELIX 69..77 FT /evidence="ECO:0007829|PDB:1TIS" FT STRAND 80..83 FT /evidence="ECO:0007829|PDB:1TIS" FT HELIX 88..91 FT /evidence="ECO:0007829|PDB:1TIS" FT TURN 92..95 FT /evidence="ECO:0007829|PDB:1TIS" FT HELIX 96..98 FT /evidence="ECO:0007829|PDB:1TIS" FT HELIX 109..114 FT /evidence="ECO:0007829|PDB:1TIS" FT HELIX 121..131 FT /evidence="ECO:0007829|PDB:1TIS" FT HELIX 145..150 FT /evidence="ECO:0007829|PDB:1TIS" FT STRAND 156..164 FT /evidence="ECO:0007829|PDB:1TIS" FT STRAND 166..179 FT /evidence="ECO:0007829|PDB:1TIS" FT TURN 180..183 FT /evidence="ECO:0007829|PDB:1TIS" FT HELIX 184..202 FT /evidence="ECO:0007829|PDB:1TIS" FT STRAND 205..221 FT /evidence="ECO:0007829|PDB:1TIS" FT TURN 224..226 FT /evidence="ECO:0007829|PDB:1TIS" FT HELIX 227..229 FT /evidence="ECO:0007829|PDB:1TIS" FT HELIX 247..251 FT /evidence="ECO:0007829|PDB:1TIS" FT HELIX 254..262 FT /evidence="ECO:0007829|PDB:1TIS" FT HELIX 266..268 FT /evidence="ECO:0007829|PDB:1TIS" SQ SEQUENCE 286 AA; 33073 MW; 9F60863145F5219D CRC64; MKQYQDLIKD IFENGYETDD RTGTGTIALF GSKLRWDLTK GFPAVTTKKL AWKACIAELI WFLSGSTNVN DLRLIQHDSL IQGKTVWDEN YENQAKDLGY HSGELGPIYG KQWRDFGGVD QIIEVIDRIK KLPNDRRQIV SAWNPAELKY MALPPCHMFY QFNVRNGYLD LQWYQRSVDV FLGLPFNIAS YATLVHIVAK MCNLIPGDLI FSGGNTHIYM NHVEQCKEIL RREPKELCEL VISGLPYKFR YLSTKEQLKY VLKLRPKDFV LNNYVSHPPI KGKMAV //