TYSY_MOUSE
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 03-AUG-2022, entry version 172.
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}.
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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; 2.
DR STRING; 10090.ENSMUSP00000026846; -.
DR BindingDB; P07607; -.
DR ChEMBL; CHEMBL3160; -.
DR DrugCentral; P07607; -.
DR GuidetoPHARMACOLOGY; 2642; -.
DR iPTMnet; P07607; -.
DR PhosphoSitePlus; P07607; -.
DR REPRODUCTION-2DPAGE; P07607; -.
DR EPD; P07607; -.
DR jPOST; P07607; -.
DR PaxDb; P07607; -.
DR PeptideAtlas; P07607; -.
DR PRIDE; P07607; -.
DR ProteomicsDB; 298158; -.
DR Antibodypedia; 3461; 1226 antibodies from 41 providers.
DR DNASU; 22171; -.
DR Ensembl; ENSMUST00000026846; ENSMUSP00000026846; ENSMUSG00000025747.
DR GeneID; 22171; -.
DR KEGG; mmu:22171; -.
DR UCSC; uc008wux.2; mouse.
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; KQYLDLC; -.
DR OrthoDB; 1197342at2759; -.
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 73 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 morula and 169 other tissues.
DR ExpressionAtlas; P07607; baseline and differential.
DR Genevisible; P07607; MM.
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:0005730; C:nucleolus; ISO:MGI.
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:0007568; P:aging; IEA:Ensembl.
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; -; 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 PANTHER; PTHR11548; PTHR11548; 1.
DR Pfam; PF00303; Thymidylat_synt; 1.
DR PRINTS; PR00108; THYMDSNTHASE.
DR SUPFAM; SSF55831; SSF55831; 1.
DR TIGRFAMs; TIGR03284; thym_sym; 1.
DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
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
