ID KITH_CRIGR Reviewed; 234 AA.
AC P09768;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 27-MAR-2024, entry version 112.
DE RecName: Full=Thymidine kinase, cytosolic;
DE EC=2.7.1.21 {ECO:0000250|UniProtKB:P04183};
GN Name=TK1;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3453109; DOI=10.1128/mcb.6.6.1998-2010.1986;
RA Lewis J.A.;
RT "Structure and expression of the Chinese hamster thymidine kinase gene.";
RL Mol. Cell. Biol. 6:1998-2010(1986).
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.
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; L00369; AAA37022.1; -; Genomic_DNA.
DR EMBL; L00364; AAA37022.1; JOINED; Genomic_DNA.
DR EMBL; L00365; AAA37022.1; JOINED; Genomic_DNA.
DR EMBL; L00366; AAA37022.1; JOINED; Genomic_DNA.
DR EMBL; L00367; AAA37022.1; JOINED; Genomic_DNA.
DR EMBL; L00368; AAA37022.1; JOINED; Genomic_DNA.
DR PIR; A25243; A25243.
DR RefSeq; NP_001231423.1; NM_001244494.2.
DR AlphaFoldDB; P09768; -.
DR SMR; P09768; -.
DR BindingDB; P09768; -.
DR ChEMBL; CHEMBL3227916; -.
DR PaxDb; 10029-NP_001231423-1; -.
DR Ensembl; ENSCGRT00000018927; ENSCGRP00000018657; ENSCGRG00000013585.
DR Ensembl; ENSCGRT00001023730.1; ENSCGRP00001019486.1; ENSCGRG00001018904.1.
DR Ensembl; ENSCGRT00015007670; ENSCGRP00015006223; ENSCGRG00015004822.
DR GeneID; 100689285; -.
DR KEGG; cge:100689285; -.
DR CTD; 7083; -.
DR eggNOG; KOG3125; Eukaryota.
DR GeneTree; ENSGT00390000011309; -.
DR OMA; EAYEPRC; -.
DR OrthoDB; 674053at2759; -.
DR Proteomes; UP000694386; Unplaced.
DR Proteomes; UP001108280; Chromosome 7.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:GOC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0004797; F:thymidine kinase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:1904860; P:DNA synthesis involved in mitotic DNA replication; IEA:Ensembl.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0046105; P:thymidine biosynthetic process; IEA:Ensembl.
DR GO; GO:0046104; P:thymidine metabolic process; ISS:UniProtKB.
DR Gene3D; 3.30.60.20; -; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR001267; Thymidine_kinase.
DR InterPro; IPR020633; Thymidine_kinase_CS.
DR PANTHER; PTHR11441; THYMIDINE KINASE; 1.
DR PANTHER; PTHR11441:SF0; THYMIDINE KINASE, CYTOSOLIC; 1.
DR Pfam; PF00265; TK; 1.
DR SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR PROSITE; PS00603; TK_CELLULAR_TYPE; 1.
PE 3: Inferred from homology;
KW ATP-binding; Cytoplasm; DNA synthesis; Kinase; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Transferase; Ubl conjugation; Zinc.
FT CHAIN 1..234
FT /note="Thymidine kinase, cytosolic"
FT /id="PRO_0000174947"
FT MOTIF 203..205
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 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04183"
SQ SEQUENCE 234 AA; 25622 MW; 8E46DC89FEAF2E9C CRC64;
MNYINLPTVL PGSPSKTRGQ IQVILGPMFS GKSTELMRRV RRFQIAQNKC LVIKYAKDTR
YSSSFSTHDR NTMDALPACL LRDVAQEALG AAVIGIDEGQ FFPDIVEFCE VMANAGKTVI
VAALDGTFQR KAFGSILNLV PLAESVVKLT AVCMECFREA AYTKRLGLEK EVEVIGGADK
YHSVCRVCYF KKSSVQPAGP DNKENCPVLG QPGEASAVRK LFAPQQVLQH NSTN
//
