KITH_CHICK
ID KITH_CHICK Reviewed; 224 AA.
AC P04047;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1986, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Thymidine kinase, cytosolic;
DE EC=2.7.1.21 {ECO:0000250|UniProtKB:P04183};
GN Name=TK1;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6328447; DOI=10.1093/nar/12.9.3959;
RA Kwoh T.J., Engler J.A.;
RT "The nucleotide sequence of the chicken thymidine kinase gene and the
RT relationship of its predicted polypeptide to that of the vaccinia virus
RT thymidine kinase.";
RL Nucleic Acids Res. 12:3959-3971(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6092937; DOI=10.1128/mcb.4.9.1769-1776.1984;
RA Merrill G.F., Harland R.M., Groudine M., McKnight S.L.;
RT "Genetic and physical analysis of the chicken tk gene.";
RL Mol. Cell. Biol. 4:1769-1776(1984).
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 P04047; P04047: TK1; NbExp=2; IntAct=EBI-8306403, EBI-8306403;
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; K02611; AAA49096.1; -; Genomic_DNA.
DR PIR; A00608; KICHT.
DR RefSeq; NP_990229.1; NM_204898.1.
DR AlphaFoldDB; P04047; -.
DR SMR; P04047; -.
DR MINT; P04047; -.
DR STRING; 9031.ENSGALP00000011630; -.
DR PaxDb; P04047; -.
DR Ensembl; ENSGALT00000011644; ENSGALP00000011630; ENSGALG00000007191.
DR Ensembl; ENSGALT00000082171; ENSGALP00000053115; ENSGALG00000007191.
DR GeneID; 395719; -.
DR KEGG; gga:395719; -.
DR CTD; 7083; -.
DR VEuPathDB; HostDB:geneid_395719; -.
DR eggNOG; KOG3125; Eukaryota.
DR GeneTree; ENSGT00390000011309; -.
DR HOGENOM; CLU_064400_3_1_1; -.
DR InParanoid; P04047; -.
DR OMA; GWLELIC; -.
DR OrthoDB; 1413914at2759; -.
DR PhylomeDB; P04047; -.
DR TreeFam; TF314839; -.
DR BRENDA; 2.7.1.21; 1306.
DR Reactome; R-GGA-73614; Pyrimidine salvage.
DR PRO; PR:P04047; -.
DR Proteomes; UP000000539; Chromosome 18.
DR Bgee; ENSGALG00000007191; Expressed in colon and 12 other tissues.
DR ExpressionAtlas; P04047; baseline and differential.
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: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 PIRSF; PIRSF035805; TK_cell; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00603; TK_CELLULAR_TYPE; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; DNA synthesis; Kinase; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation; Zinc.
FT CHAIN 1..224
FT /note="Thymidine kinase, cytosolic"
FT /id="PRO_0000174946"
FT MOTIF 203..205
FT /note="KEN box"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT ACT_SITE 99
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 98..101
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 129
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 157
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 173..177
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 182
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 186
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 189
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 224 AA; 24872 MW; BF29BEED2892BCF6 CRC64;
MNCLTVPGVH PGSPGRPRGQ IQVIFGPMFS GKSTELMRRV RRFQLAQYRC LLVKYAKDTR
YCTTGVSTHD RNTMEARPAC ALQDVYQEAL GSAVIGIDEG QFFPDIVEFC EKMANTGKTV
IVAALDGTFQ RKAFGSILNL VPLAESVVKL NAVCMECYRE ASYTKRLGAE REVEVIGGAD
KYHSVCRACY FQKRPQQLGS ENKENVPMGV KQLDMPASRK IFAS
