P09768 · KITH_CRIGR

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

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site26-33ATP (UniProtKB | ChEBI)
Binding site58-60ATP (UniProtKB | ChEBI)
Binding site97-100ATP (UniProtKB | ChEBI)
Active site98Proton acceptor
Binding site128substrate
Binding site153Zn2+ (UniProtKB | ChEBI)
Binding site156Zn2+ (UniProtKB | ChEBI)
Binding site172-176substrate
Binding site181substrate
Binding site185Zn2+ (UniProtKB | ChEBI)
Binding site188Zn2+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentnucleus
Molecular FunctionATP binding
Molecular Functionidentical protein binding
Molecular Functionthymidine kinase activity
Molecular Functionzinc ion binding
Biological ProcessDNA synthesis involved in mitotic DNA replication
Biological Processprotein homotetramerization
Biological Processthymidine biosynthetic process
Biological Processthymidine metabolic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Thymidine kinase, cytosolic
  • EC number

Gene names

    • Name
      TK1

Organism names

Accessions

  • Primary accession
    P09768

Proteomes

Subcellular Location

Keywords

Phenotypes & Variants

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00001749471-234Thymidine kinase, cytosolic
Modified residue13Phosphoserine

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

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.

Chemistry

Structure

Family & Domains

Features

Showing features for motif.

TypeIDPosition(s)Description
Motif203-205KEN box

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 status
    Complete
  • Length
    234
  • Mass (Da)
    25,622
  • Last updated
    1989-07-01 v1
  • Checksum
    8E46DC89FEAF2E9C
MNYINLPTVLPGSPSKTRGQIQVILGPMFSGKSTELMRRVRRFQIAQNKCLVIKYAKDTRYSSSFSTHDRNTMDALPACLLRDVAQEALGAAVIGIDEGQFFPDIVEFCEVMANAGKTVIVAALDGTFQRKAFGSILNLVPLAESVVKLTAVCMECFREAAYTKRLGLEKEVEVIGGADKYHSVCRVCYFKKSSVQPAGPDNKENCPVLGQPGEASAVRKLFAPQQVLQHNSTN

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
L00369
EMBL· GenBank· DDBJ
AAA37022.1
EMBL· GenBank· DDBJ
Genomic DNA
L00364
EMBL· GenBank· DDBJ
AAA37022.1
EMBL· GenBank· DDBJ
Genomic DNA
L00365
EMBL· GenBank· DDBJ
AAA37022.1
EMBL· GenBank· DDBJ
Genomic DNA
L00366
EMBL· GenBank· DDBJ
AAA37022.1
EMBL· GenBank· DDBJ
Genomic DNA
L00367
EMBL· GenBank· DDBJ
AAA37022.1
EMBL· GenBank· DDBJ
Genomic DNA
L00368
EMBL· GenBank· DDBJ
AAA37022.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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