A5D7R8 · KITH_BOVIN
- ProteinThymidine kinase, cytosolic
- GeneTK1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids238 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score4/5
Function
function
Cell-cycle-regulated enzyme of importance in nucleotide metabolism. Catalyzes the first enzymatic step in the salvage pathway converting thymidine into thymidine monophosphate. Transcriptional regulation limits expression to the S phase of the cell cycle and transient expression coincides with the oscillation in the intracellular dTTP concentration.
Miscellaneous
Two forms have been identified in animal cells, one in cytosol and one in mitochondria. Activity of the cytosolic enzyme is high in proliferating cells and peaks during the S-phase of the cell cycle; it is very low in resting cells.
Catalytic activity
- ATP + thymidine = ADP + dTMP + H+This reaction proceeds in the forward direction.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 26-33 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GPMFSGKS | ||||||
Binding site | 58-60 | ATP (UniProtKB | ChEBI) | ||||
Sequence: DTR | ||||||
Binding site | 97-100 | ATP (UniProtKB | ChEBI) | ||||
Sequence: DEGQ | ||||||
Active site | 98 | Proton acceptor | ||||
Sequence: E | ||||||
Binding site | 128 | substrate | ||||
Sequence: F | ||||||
Binding site | 153 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 156 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 172-176 | substrate | ||||
Sequence: VEVIG | ||||||
Binding site | 181 | substrate | ||||
Sequence: Y | ||||||
Binding site | 185 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 188 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Molecular Function | ATP binding | |
Molecular Function | thymidine kinase activity | |
Molecular Function | zinc ion binding | |
Biological Process | DNA biosynthetic process | |
Biological Process | protein homotetramerization | |
Biological Process | thymidine metabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameThymidine kinase, cytosolic
- EC number
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos
Accessions
- Primary accessionA5D7R8
- Secondary accessions
Proteomes
Subcellular Location
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylserine | ||||
Sequence: S | ||||||
Modified residue | 2 | Phosphoserine | ||||
Sequence: S | ||||||
Chain | PRO_0000322129 | 2-238 | Thymidine kinase, cytosolic | |||
Sequence: SCINLPNVLPGSPSKTRGQIQVILGPMFSGKSTELMRRVRRFQVAQYKCLVIKYAKDTRYSSLFSTHDRNTMEALPACLLRDVIQDAQRVAVIGIDEGQFFPDIVEFCENMANSGKTVIVAALDGTFQRKAFGTILNLVPLAESVVKLTAVCMECFREAAYTKRLGVEKEVEVIGGADKYHSVCRLCYFKKASGQPAVLDSEENKENCPMTLGKPAEAPGVRKLFATHQIWQCSQAN | ||||||
Modified residue | 13 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 235 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated on Ser-13 in mitosis. Phosphorylation of Ser-13 by CDK1 during mitosis reduces homotetramerization and catalytic efficiency when DNA replication is complete and intracellular TK1 is still present at a high level.
Polyubiquitinated. Postmitosis, ubiquitination leads to proteasomal degradation. The KEN box sequence located at the C-terminal region targets for degradation by the anaphase promoting complex (APC/C) activated and rate-limited by FZR1.
Keywords
- PTM
Proteomic databases
Interaction
Subunit
Homotetramer. Tetramerization from dimerization is induced by ATP and increases catalytic efficiency due to a high affinity for thymidine. Tetramerization is inhibited by phosphorylation at Ser-13. Interacts (via the KEN box) with FZR1.
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 206-208 | KEN box | ||||
Sequence: KEN |
Domain
KEN box sequence located in the C-terminal region is required for its mitotic degradation by the APC/C-FZR1 ubiquitin ligase and interaction capability with FZR1.
Sequence similarities
Belongs to the thymidine kinase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length238
- Mass (Da)26,377
- Last updated2007-06-12 v1
- ChecksumB9D720679A18C452
Sequence caution
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
BT030694 EMBL· GenBank· DDBJ | ABS45010.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC140658 EMBL· GenBank· DDBJ | AAI40659.1 EMBL· GenBank· DDBJ | mRNA |