ID TYSY_HAEIN Reviewed; 283 AA. AC P44420; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 27-MAR-2024, entry version 137. 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=HI_0905; OS Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Pasteurellales; OC Pasteurellaceae; Haemophilus. OX NCBI_TaxID=71421; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd; RX PubMed=7542800; DOI=10.1126/science.7542800; RA Fleischmann R.D., Adams M.D., White O., Clayton R.A., Kirkness E.F., RA Kerlavage A.R., Bult C.J., Tomb J.-F., Dougherty B.A., Merrick J.M., RA McKenney K., Sutton G.G., FitzHugh W., Fields C.A., Gocayne J.D., RA Scott J.D., Shirley R., Liu L.-I., Glodek A., Kelley J.M., Weidman J.F., RA Phillips C.A., Spriggs T., Hedblom E., Cotton M.D., Utterback T.R., RA Hanna M.C., Nguyen D.T., Saudek D.M., Brandon R.C., Fine L.D., RA Fritchman J.L., Fuhrmann J.L., Geoghagen N.S.M., Gnehm C.L., McDonald L.A., RA Small K.V., Fraser C.M., Smith H.O., Venter J.C.; RT "Whole-genome random sequencing and assembly of Haemophilus influenzae RT Rd."; RL Science 269:496-512(1995). 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}. 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; L42023; AAC22564.1; -; Genomic_DNA. DR PIR; G64101; G64101. DR RefSeq; NP_439065.1; NC_000907.1. DR AlphaFoldDB; P44420; -. DR SMR; P44420; -. DR STRING; 71421.HI_0905; -. DR EnsemblBacteria; AAC22564; AAC22564; HI_0905. DR KEGG; hin:HI_0905; -. DR PATRIC; fig|71421.8.peg.946; -. DR eggNOG; COG0207; Bacteria. DR HOGENOM; CLU_021669_0_1_6; -. DR OrthoDB; 9774633at2; -. DR PhylomeDB; P44420; -. DR BioCyc; HINF71421:G1GJ1-944-MONOMER; -. DR UniPathway; UPA00575; -. DR Proteomes; UP000000579; Chromosome. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0004799; F:thymidylate synthase activity; IBA:GO_Central. DR GO; GO:0006231; P:dTMP biosynthetic process; IBA:GO_Central. 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: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..283 FT /note="Thymidylate synthase" FT /id="PRO_0000140963" FT ACT_SITE 160 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 22 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 180..183 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 183 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 191 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 221..223 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008" FT BINDING 282 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 283 AA; 32460 MW; C1B6763651B1C233 CRC64; MKQYLELCRR IVSEGEWVAN ERTGKHCLTV INADLEYDVA NNQFPLITTR KSYWKAAIAE FLGYIRGYDN AADFRALGTK TWDANANENA AWLANPHRRG VDDMGRVYGV QGRAWRKPNG ETIDQLRKIV NNLTKGIDDR GEILTFFNPG EFDLGCLRPC MHTHTFSLVG DTLHLTSYQR SCDVPLGLNF NQIQVFTFLA LMAQITGKKA GKAYHKIVNA HIYEDQLELM RDVQLKREPF PLPKLEINPD IKTLEDLETW VTMDDFKVVG YQSHEPIKYP FSV //