ID TYSY_BOVIN Reviewed; 354 AA. AC Q2TA32; Q9N1D3; DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2006, sequence version 1. DT 08-NOV-2023, entry version 101. DE RecName: Full=Thymidylate synthase; DE Short=TS; DE Short=TSase; DE EC=2.1.1.45 {ECO:0000250|UniProtKB:P04818}; GN Name=TYMS; Synonyms=TS; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Crossbred X Angus; TISSUE=Liver; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 211-255. RX PubMed=11130975; DOI=10.1007/s003350010220; RA Brouillette J.A., Andrew J.R., Venta P.J.; RT "Estimate of nucleotide diversity in dogs with a pool-and-sequence RT method."; RL Mamm. Genome 11:1079-1086(2000). CC -!- FUNCTION: Catalyzes the reductive methylation of 2'-deoxyuridine 5'- CC monophosphate (dUMP) to thymidine 5'-monophosphate (dTMP), using the CC cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1- CC carbon donor and reductant and contributes to the de novo mitochondrial CC thymidylate biosynthesis pathway. {ECO:0000250|UniProtKB:P04818}. 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:0000250|UniProtKB:P04818}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12105; CC Evidence={ECO:0000250|UniProtKB:P04818}; CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis. CC {ECO:0000250|UniProtKB:P04818}. CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P45352}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P04818}. Cytoplasm CC {ECO:0000250|UniProtKB:P04818}. Mitochondrion CC {ECO:0000250|UniProtKB:P04818}. Mitochondrion matrix CC {ECO:0000250|UniProtKB:P04818}. Mitochondrion inner membrane CC {ECO:0000250|UniProtKB:P04818}. 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; BC111139; AAI11140.1; -; mRNA. DR EMBL; AH009263; AAF66224.1; -; Genomic_DNA. DR RefSeq; NP_001032905.1; NM_001037816.1. DR AlphaFoldDB; Q2TA32; -. DR SMR; Q2TA32; -. DR STRING; 9913.ENSBTAP00000009214; -. DR BindingDB; Q2TA32; -. DR ChEMBL; CHEMBL3243905; -. DR PaxDb; 9913-ENSBTAP00000009214; -. DR GeneID; 507631; -. DR KEGG; bta:507631; -. DR CTD; 7298; -. DR eggNOG; KOG0673; Eukaryota. DR InParanoid; Q2TA32; -. DR OrthoDB; 1118873at2759; -. DR UniPathway; UPA00575; -. DR Proteomes; UP000009136; Unplaced. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. 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:SF2; THYMIDYLATE SYNTHASE; 1. DR PANTHER; PTHR11548; THYMIDYLATE SYNTHASE 1; 1. DR Pfam; PF00303; Thymidylat_synt; 2. DR PRINTS; PR00108; THYMDSNTHASE. DR SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 2. DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1. PE 2: Evidence at transcript level; KW Cytoplasm; Isopeptide bond; Membrane; Methyltransferase; Mitochondrion; KW Mitochondrion inner membrane; Nucleotide biosynthesis; Nucleus; KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation. FT CHAIN 1..354 FT /note="Thymidylate synthase" FT /id="PRO_0000317541" FT REGION 1..32 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 198 FT /note="Nucleophile" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT BINDING 53 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 178..179 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 218..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:0000250|UniProtKB:P0A884" FT BINDING 221 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 229 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 259..261 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 353 FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:15636" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT MOD_RES 117 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04818" FT CROSSLNK 349 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P04818" SQ SEQUENCE 354 AA; 39785 MW; 2350409479AF4C40 CRC64; MPAAGSEPSR PPSPPGVQEQ SAEPRPPPPP HGELQYLGQI EHILRCGFRR DDRTGTGTLS VFGMQARYNL RDEFPLLTTK RVFWKGVLEE LLWFIKGSTN AKELSSKGVK IWDANGSRDF LDGLGFSDRA EGDLGPVYGF QWRHFGAEYK DMDSEYSGQG VDQLQKVIDT IKTNPNDRRI ILCAWNPKDL PLMALPPCHA LCQFYVVNGE LSCQLYQRSG DMGLGVPFNI ASYALLTYMI AHITDLKPGD FVHTLGDAHI YLNHIEPLKT QALMELRGQS SRSLDGDGQA GTSRWAPVAT DTERDRCCEL QREPRPFPKL KILRKVETID DFQAEDFQIE GYNPNPTIKM EMAV //