ID KITH_BOVIN Reviewed; 238 AA. AC A5D7R8; A7E3S3; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 12-JUN-2007, sequence version 1. DT 03-AUG-2022, entry version 86. DE RecName: Full=Thymidine kinase, cytosolic; DE EC=2.7.1.21 {ECO:0000250|UniProtKB:P04183}; GN Name=TK1; 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]. RX PubMed=16305752; DOI=10.1186/1471-2164-6-166; RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.; RT "Characterization of 954 bovine full-CDS cDNA sequences."; RL BMC Genomics 6:166-166(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Fetal liver; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Cell-cycle-regulated enzyme of importance in nucleotide CC metabolism. Catalyzes the first enzymatic step in the salvage pathway CC converting thymidine into thymidine monophosphate. Transcriptional CC regulation limits expression to the S phase of the cell cycle and CC transient expression coincides with the oscillation in the CC intracellular dTTP concentration. {ECO:0000250|UniProtKB:P04183}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + thymidine = ADP + dTMP + H(+); Xref=Rhea:RHEA:19129, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17748, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:63528, ChEBI:CHEBI:456216; EC=2.7.1.21; CC Evidence={ECO:0000250|UniProtKB:P04183}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19130; CC Evidence={ECO:0000250|UniProtKB:P04183}; CC -!- SUBUNIT: Homotetramer. Tetramerization from dimerization is induced by CC ATP and increases catalytic efficiency due to a high affinity for CC thymidine. Tetramerization is inhibited by phosphorylation at Ser-13. CC Interacts (via the KEN box) with FZR1. {ECO:0000250|UniProtKB:P04183}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. CC -!- DOMAIN: KEN box sequence located in the C-terminal region is required CC for its mitotic degradation by the APC/C-FZR1 ubiquitin ligase and CC interaction capability with FZR1. {ECO:0000250|UniProtKB:P04183}. CC -!- PTM: Phosphorylated on Ser-13 in mitosis. Phosphorylation of Ser-13 by CC CDK1 during mitosis reduces homotetramerization and catalytic CC efficiency when DNA replication is complete and intracellular TK1 is CC still present at a high level. {ECO:0000250|UniProtKB:P04183}. CC -!- PTM: Polyubiquitinated. Postmitosis, ubiquitination leads to CC proteasomal degradation. The KEN box sequence located at the C-terminal CC region targets for degradation by the anaphase promoting complex CC (APC/C) activated and rate-limited by FZR1. CC {ECO:0000250|UniProtKB:P04183}. CC -!- MISCELLANEOUS: Two forms have been identified in animal cells, one in CC cytosol and one in mitochondria. Activity of the cytosolic enzyme is CC high in proliferating cells and peaks during the S-phase of the cell CC cycle; it is very low in resting cells. CC -!- SIMILARITY: Belongs to the thymidine kinase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=ABS45010.1; Type=Erroneous initiation; Evidence={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; BT030694; ABS45010.1; ALT_INIT; mRNA. DR EMBL; BC140658; AAI40659.1; -; mRNA. DR RefSeq; NP_001091041.1; NM_001097572.1. DR AlphaFoldDB; A5D7R8; -. DR SMR; A5D7R8; -. DR STRING; 9913.ENSBTAP00000034599; -. DR PaxDb; A5D7R8; -. DR PRIDE; A5D7R8; -. DR GeneID; 504652; -. DR KEGG; bta:504652; -. DR CTD; 7083; -. DR eggNOG; KOG3125; Eukaryota. DR HOGENOM; CLU_064400_3_1_1; -. DR InParanoid; A5D7R8; -. DR OrthoDB; 1413914at2759; -. DR TreeFam; TF314839; -. DR Proteomes; UP000009136; Unplaced. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004797; F:thymidine kinase activity; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0071897; P:DNA biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB. DR GO; GO:0046104; P:thymidine metabolic process; ISS:UniProtKB. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR001267; Thymidine_kinase. DR InterPro; IPR020633; Thymidine_kinase_CS. DR PANTHER; PTHR11441; PTHR11441; 1. DR Pfam; PF00265; TK; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS00603; TK_CELLULAR_TYPE; 1. PE 2: Evidence at transcript level; KW Acetylation; ATP-binding; Cytoplasm; DNA synthesis; Kinase; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase; KW Ubl conjugation; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P04183" FT CHAIN 2..238 FT /note="Thymidine kinase, cytosolic" FT /id="PRO_0000322129" FT MOTIF 206..208 FT /note="KEN box" FT /evidence="ECO:0000250|UniProtKB:P04183" FT ACT_SITE 98 FT /note="Proton acceptor" FT /evidence="ECO:0000255" FT BINDING 26..33 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305" FT BINDING 58..60 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04183" FT BINDING 97..100 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04183" FT BINDING 128 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P04183" FT BINDING 153 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P04183" FT BINDING 156 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P04183" FT BINDING 172..176 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P04183" FT BINDING 181 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P04183" FT BINDING 185 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P04183" FT BINDING 188 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P04183" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000250|UniProtKB:P04183" FT MOD_RES 2 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04183" FT MOD_RES 13 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04183" FT MOD_RES 235 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04183" SQ SEQUENCE 238 AA; 26377 MW; B9D720679A18C452 CRC64; MSCINLPNVL PGSPSKTRGQ IQVILGPMFS GKSTELMRRV RRFQVAQYKC LVIKYAKDTR YSSLFSTHDR NTMEALPACL LRDVIQDAQR VAVIGIDEGQ FFPDIVEFCE NMANSGKTVI VAALDGTFQR KAFGTILNLV PLAESVVKLT AVCMECFREA AYTKRLGVEK EVEVIGGADK YHSVCRLCYF KKASGQPAVL DSEENKENCP MTLGKPAEAP GVRKLFATHQ IWQCSQAN //