ID TYSY_MOUSE Reviewed; 307 AA. AC P07607; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1988, sequence version 1. DT 27-MAR-2024, entry version 181. DE RecName: Full=Thymidylate synthase; DE Short=TS; DE Short=TSase; DE EC=2.1.1.45 {ECO:0000250|UniProtKB:P04818}; GN Name=Tyms; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3444407; DOI=10.1093/oxfordjournals.molbev.a040400; RA Perryman S.M., Rossana C., Deng T., Vanin E.F., Johnson L.F.; RT "Sequence of a cDNA for mouse thymidylate synthase reveals striking RT similarity with the prokaryotic enzyme."; RL Mol. Biol. Evol. 3:313-321(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3782103; DOI=10.1016/s0021-9258(18)66666-9; RA Deng T., Li D., Jenh C.-H., Johnson L.F.; RT "Structure of the gene for mouse thymidylate synthase. Locations of introns RT and multiple transcriptional start sites."; RL J. Biol. Chem. 261:16000-16005(1986). RN [3] RP NUCLEOTIDE SEQUENCE OF 236-265. RX PubMed=2915925; DOI=10.1093/nar/17.2.645; RA Deng T., Li Y., Johnson L.F.; RT "Thymidylate synthase gene expression is stimulated by some (but not all) RT introns."; RL Nucleic Acids Res. 17:645-658(1989). RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Kidney, and Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). 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:P45352}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12105; CC Evidence={ECO:0000250|UniProtKB:P45352}; CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis. CC {ECO:0000250|UniProtKB:P45352}. 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; M13019; AAA40439.1; -; mRNA. DR EMBL; M13352; AAA40444.1; -; Genomic_DNA. DR EMBL; J02617; AAA40444.1; JOINED; Genomic_DNA. DR EMBL; M13347; AAA40444.1; JOINED; Genomic_DNA. DR EMBL; M13348; AAA40444.1; JOINED; Genomic_DNA. DR EMBL; M13349; AAA40444.1; JOINED; Genomic_DNA. DR EMBL; M13350; AAA40444.1; JOINED; Genomic_DNA. DR EMBL; M13351; AAA40444.1; JOINED; Genomic_DNA. DR EMBL; X14489; CAA32651.1; -; mRNA. DR CCDS; CCDS19154.1; -. DR PIR; A26323; YXMST. DR RefSeq; NP_067263.1; NM_021288.4. DR PDB; 3IHI; X-ray; 1.94 A; A/B=1-307. DR PDB; 4E5O; X-ray; 1.70 A; A/B/C/D/E/F=1-307. DR PDB; 4EB4; X-ray; 1.74 A; A/B/C/D=1-307. DR PDB; 4EIN; X-ray; 1.75 A; A/B=1-307. DR PDB; 4EZ8; X-ray; 1.17 A; A=1-307. DR PDB; 5FCT; X-ray; 1.55 A; A/B=1-307. DR PDB; 6F6Z; X-ray; 2.13 A; A/B=1-307. DR PDB; 6GKO; X-ray; 1.84 A; A/B=1-307. DR PDB; 6GYJ; X-ray; 1.75 A; A/B=1-307. DR PDB; 6Y08; X-ray; 2.30 A; A/B=1-307. DR PDBsum; 3IHI; -. DR PDBsum; 4E5O; -. DR PDBsum; 4EB4; -. DR PDBsum; 4EIN; -. DR PDBsum; 4EZ8; -. DR PDBsum; 5FCT; -. DR PDBsum; 6F6Z; -. DR PDBsum; 6GKO; -. DR PDBsum; 6GYJ; -. DR PDBsum; 6Y08; -. DR AlphaFoldDB; P07607; -. DR SMR; P07607; -. DR BioGRID; 204392; 3. DR STRING; 10090.ENSMUSP00000026846; -. DR BindingDB; P07607; -. DR ChEMBL; CHEMBL3160; -. DR DrugCentral; P07607; -. DR GuidetoPHARMACOLOGY; 2642; -. DR GlyGen; P07607; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P07607; -. DR PhosphoSitePlus; P07607; -. DR REPRODUCTION-2DPAGE; P07607; -. DR EPD; P07607; -. DR jPOST; P07607; -. DR PaxDb; 10090-ENSMUSP00000026846; -. DR PeptideAtlas; P07607; -. DR ProteomicsDB; 298158; -. DR Pumba; P07607; -. DR Antibodypedia; 3461; 1366 antibodies from 41 providers. DR DNASU; 22171; -. DR Ensembl; ENSMUST00000026846.11; ENSMUSP00000026846.7; ENSMUSG00000025747.13. DR GeneID; 22171; -. DR KEGG; mmu:22171; -. DR UCSC; uc008wux.2; mouse. DR AGR; MGI:98878; -. DR CTD; 7298; -. DR MGI; MGI:98878; Tyms. DR VEuPathDB; HostDB:ENSMUSG00000025747; -. DR eggNOG; KOG0673; Eukaryota. DR GeneTree; ENSGT00390000014786; -. DR HOGENOM; CLU_021669_0_2_1; -. DR InParanoid; P07607; -. DR OMA; IVYELLW; -. DR OrthoDB; 1118873at2759; -. DR PhylomeDB; P07607; -. DR TreeFam; TF353027; -. DR BRENDA; 2.1.1.45; 3474. DR Reactome; R-MMU-499943; Interconversion of nucleotide di- and triphosphates. DR UniPathway; UPA00575; -. DR BioGRID-ORCS; 22171; 25 hits in 77 CRISPR screens. DR ChiTaRS; Tyms; mouse. DR EvolutionaryTrace; P07607; -. DR PRO; PR:P07607; -. DR Proteomes; UP000000589; Chromosome 5. DR RNAct; P07607; Protein. DR Bgee; ENSMUSG00000025747; Expressed in blastoderm cell in morula and 172 other cell types or tissues. DR ExpressionAtlas; P07607; baseline and differential. 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; IDA:MGI. DR GO; GO:0005542; F:folic acid binding; ISO:MGI. DR GO; GO:1901363; F:heterocyclic compound binding; ISO:MGI. DR GO; GO:0003729; F:mRNA binding; ISO:MGI. DR GO; GO:0000900; F:mRNA regulatory element binding translation repressor activity; ISO:MGI. DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI. DR GO; GO:1990825; F:sequence-specific mRNA binding; ISO:MGI. DR GO; GO:0004799; F:thymidylate synthase activity; IDA:MGI. DR GO; GO:0051216; P:cartilage development; IEA:Ensembl. DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl. DR GO; GO:0048589; P:developmental growth; IEA:Ensembl. DR GO; GO:0006231; P:dTMP biosynthetic process; IDA:MGI. DR GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0060574; P:intestinal epithelial cell maturation; IEA:Ensembl. DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0017148; P:negative regulation of translation; ISO:MGI. DR GO; GO:0006417; P:regulation of translation; ISO:MGI. DR GO; GO:0034097; P:response to cytokine; IEA:Ensembl. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0051593; P:response to folic acid; IEA:Ensembl. DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl. DR GO; GO:0046683; P:response to organophosphorus; IEA:Ensembl. DR GO; GO:0032570; P:response to progesterone; IEA:Ensembl. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0033189; P:response to vitamin A; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0035999; P:tetrahydrofolate interconversion; IDA:MGI. DR GO; GO:0019860; P:uracil metabolic process; IEA:Ensembl. 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; 1. DR PRINTS; PR00108; THYMDSNTHASE. DR SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 1. DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1. DR Genevisible; P07607; MM. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Isopeptide bond; Membrane; Methyltransferase; KW Mitochondrion; Mitochondrion inner membrane; Nucleotide biosynthesis; KW Nucleus; Phosphoprotein; Reference proteome; Transferase; Ubl conjugation. FT CHAIN 1..307 FT /note="Thymidylate synthase" FT /id="PRO_0000140902" FT ACT_SITE 189 FT /note="Nucleophile" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT BINDING 44 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 169..170 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:P45352" FT BINDING 189..190 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:P45352" FT BINDING 209..212 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:P45352" FT BINDING 212 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 220 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 250..252 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:P45352" FT BINDING 306 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 108 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04818" FT CROSSLNK 286 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P04818" FT CROSSLNK 302 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P04818" FT HELIX 24..37 FT /evidence="ECO:0007829|PDB:4EZ8" FT STRAND 39..41 FT /evidence="ECO:0007829|PDB:4EZ8" FT STRAND 44..47 FT /evidence="ECO:0007829|PDB:4EIN" FT STRAND 49..60 FT /evidence="ECO:0007829|PDB:4EZ8" FT STRAND 62..64 FT /evidence="ECO:0007829|PDB:4EZ8" FT STRAND 69..71 FT /evidence="ECO:0007829|PDB:4EZ8" FT HELIX 75..86 FT /evidence="ECO:0007829|PDB:4EZ8" FT HELIX 92..96 FT /evidence="ECO:0007829|PDB:4EZ8" FT TURN 97..99 FT /evidence="ECO:0007829|PDB:4EZ8" FT TURN 102..107 FT /evidence="ECO:0007829|PDB:4EZ8" FT HELIX 109..114 FT /evidence="ECO:0007829|PDB:4EZ8" FT STRAND 118..120 FT /evidence="ECO:0007829|PDB:6Y08" FT HELIX 129..135 FT /evidence="ECO:0007829|PDB:4EZ8" FT HELIX 154..164 FT /evidence="ECO:0007829|PDB:4EZ8" FT STRAND 172..174 FT /evidence="ECO:0007829|PDB:4EZ8" FT TURN 178..180 FT /evidence="ECO:0007829|PDB:4EZ8" FT HELIX 181..183 FT /evidence="ECO:0007829|PDB:4EZ8" FT STRAND 184..186 FT /evidence="ECO:0007829|PDB:4E5O" FT STRAND 189..198 FT /evidence="ECO:0007829|PDB:4EZ8" FT STRAND 201..212 FT /evidence="ECO:0007829|PDB:4EZ8" FT TURN 213..215 FT /evidence="ECO:0007829|PDB:4EZ8" FT HELIX 216..235 FT /evidence="ECO:0007829|PDB:4EZ8" FT STRAND 238..252 FT /evidence="ECO:0007829|PDB:4EZ8" FT HELIX 253..255 FT /evidence="ECO:0007829|PDB:4EZ8" FT HELIX 256..263 FT /evidence="ECO:0007829|PDB:4EZ8" FT STRAND 272..275 FT /evidence="ECO:0007829|PDB:4EZ8" FT HELIX 282..284 FT /evidence="ECO:0007829|PDB:4EZ8" FT HELIX 287..289 FT /evidence="ECO:0007829|PDB:4EZ8" FT STRAND 290..294 FT /evidence="ECO:0007829|PDB:4EZ8" SQ SEQUENCE 307 AA; 34958 MW; E4930618C487FD5E CRC64; MLVVGSELQS DAQQLSAEAP RHGELQYLRQ VEHILRCGFK KEDRTGTGTL SVFGMQARYS LRDEFPLLTT KRVFWKGVLE ELLWFIKGST NAKELSSKGV RIWDANGSRD FLDSLGFSAR QEGDLGPVYG FQWRHFGAEY KDMDSDYSGQ GVDQLQKVID TIKTNPDDRR IIMCAWNPKD LPLMALPPCH ALCQFYVVNG ELSCQLYQRS GDMGLGVPFN IASYALLTYM IAHITGLQPG DFVHTLGDAH IYLNHIEPLK IQLQREPRPF PKLKILRKVE TIDDFKVEDF QIEGYNPHPT IKMEMAV //