KITH_RAT
ID KITH_RAT Reviewed; 121 AA.
AC P27158; Q6LAG4;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Thymidine kinase, cytosolic;
DE EC=2.7.1.21 {ECO:0000250|UniProtKB:P04183};
DE Flags: Fragment;
GN Name=Tk1; Synonyms=Tk-1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3479791; DOI=10.1073/pnas.84.23.8277;
RA Murphy A.J.M., Efstratiadis A.;
RT "Cloning vectors for expression of cDNA libraries in mammalian cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:8277-8281(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-44.
RC STRAIN=Sprague-Dawley;
RA Sauer M.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-32.
RC TISSUE=Liver;
RX PubMed=1777676; DOI=10.3109/10425179109039682;
RA Arcot S., Traina-Dorge V.L., Deininger P.L.;
RT "The rat thymidine kinase gene 5' region: evolution of a promoter.";
RL DNA Seq. 2:129-131(1991).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 -!- INTERACTION:
CC P27158; P27158: Tk1; NbExp=2; IntAct=EBI-8306437, EBI-8306437;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
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}.
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DR EMBL; M22642; AAA75560.1; -; mRNA.
DR EMBL; Y17296; CAA76733.1; -; Genomic_DNA.
DR EMBL; X54173; CAA38106.1; -; Genomic_DNA.
DR PIR; A39968; A39968.
DR RefSeq; NP_434687.1; NM_052800.1.
DR AlphaFoldDB; P27158; -.
DR SMR; P27158; -.
DR IntAct; P27158; 1.
DR MINT; P27158; -.
DR STRING; 10116.ENSRNOP00000067459; -.
DR BindingDB; P27158; -.
DR ChEMBL; CHEMBL4022; -.
DR PaxDb; P27158; -.
DR GeneID; 24834; -.
DR KEGG; rno:24834; -.
DR CTD; 7083; -.
DR RGD; 621014; Tk1.
DR eggNOG; KOG3125; Eukaryota.
DR InParanoid; P27158; -.
DR OrthoDB; 1413914at2759; -.
DR PhylomeDB; P27158; -.
DR BRENDA; 2.7.1.21; 5301.
DR SABIO-RK; P27158; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004797; F:thymidine kinase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0048565; P:digestive tract development; IEP:RGD.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0060138; P:fetal process involved in parturition; IEP:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0046688; P:response to copper ion; IEP:RGD.
DR GO; GO:0051414; P:response to cortisol; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0014856; P:skeletal muscle cell proliferation; IEP:RGD.
DR GO; GO:0046104; P:thymidine metabolic process; IDA:RGD.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR001267; Thymidine_kinase.
DR PANTHER; PTHR11441; PTHR11441; 1.
DR Pfam; PF00265; TK; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cytoplasm; DNA synthesis; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT CHAIN 2..>121
FT /note="Thymidine kinase, cytosolic"
FT /id="PRO_0000174950"
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 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 NON_TER 121
SQ SEQUENCE 121 AA; 13511 MW; 8330BDFD9CDA9EB0 CRC64;
MSYINLPTVL PISPSKTRGQ IQVILGPMFS GKSTELMRRV RRFQIAQYKC LVIKYAKDTR
YSNSFSTHDR NTMDALPACM LKDVAQEALG VAVIGIDEGQ FFPDIVDFCE TMANTGKTVI
V
