TYSY_BOVIN
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 03-AUG-2022, entry version 96.
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}.
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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; Q2TA32; -.
DR PRIDE; Q2TA32; -.
DR GeneID; 507631; -.
DR KEGG; bta:507631; -.
DR CTD; 7298; -.
DR eggNOG; KOG0673; Eukaryota.
DR InParanoid; Q2TA32; -.
DR OrthoDB; 1197342at2759; -.
DR UniPathway; UPA00575; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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; IEA:UniProtKB-EC.
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; -; 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; 2.
DR PRINTS; PR00108; THYMDSNTHASE.
DR SUPFAM; SSF55831; SSF55831; 2.
DR TIGRFAMs; TIGR03284; thym_sym; 1.
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
