UniProt:P04183 TK1

chain
  • initiator methionine:1
  • chain:2-234
checksum 76901415C631EF21
comment
  • FUNCTION Cell-cycle-regulated enzyme of importance in nucleotide metabolism (PubMed:9575153). Catalyzes the first enzymatic step in the salvage pathway converting thymidine into thymidine monophosphate (PubMed:22385435). Transcriptional regulation limits expression to the S phase of the cell cycle and transient expression coincides with the oscillation in the intracellular dTTP concentration (Probable). Also important for the activation of anticancer and antiviral nucleoside analog prodrugs such as 1-b-d-arabinofuranosylcytosine (AraC) and 3c-azido-3c-deoxythymidine (AZT) (PubMed:22385435).CATALYTIC ACTIVITY thymidine + ATP = dTMP + ADP + H(+)BIOPHYSICOCHEMICAL PROPERTIES Kcats are 9.5 sec(-1) and 3.5 sec(-1) with thymidine and AZT as substrates, respectively (PubMed:22385435). Kcat is 282 min(-1) with thymidine (PubMed:14697231).SUBUNIT Homotetramer (PubMed:14697231, PubMed:15611477, PubMed:15733844, PubMed:17407781, PubMed:22385435). Tetramerization from dimerization is induced by ATP and increases catalytic efficiency due to a high affinity for thymidine (PubMed:14697231). Tetramerization is inhibited by phosphorylation at Ser-13 (PubMed:14697231). Interacts (via the KEN box) with FZR1 (PubMed:14701726).INTERACTION Significantly increased in the cells during progression to the S and M phases, and becomes barely detectable in the early G(1) phase by a proteolytic control during mitotic exit.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.PTM 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 (PubMed:14697231, PubMed:9575153).PTM 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.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.SIMILARITY Belongs to the thymidine kinase family.
crossReference
databaseName UniProt
dbId 69804
description
  • recommendedName: fullName evidence="9"Thymidine kinase, cytosolic ecNumber evidence="2 7"2.7.1.21
displayName UniProt:P04183 TK1
geneName
  • TK1
identifier P04183
isSequenceChanged false
keyword
  • 3D-structure
  • Acetylation
  • ATP-binding
  • Cytoplasm
  • DNA synthesis
  • Kinase
  • Metal-binding
  • Nucleotide-binding
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Transferase
  • Ubl conjugation
  • Zinc
modified [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
moleculeType Protein
name
  • TK1
otherIdentifier
  • 11718127_at
  • 11718128_x_at
  • 1554408_PM_a_at
  • 1554408_a_at
  • 16849379
  • 202338_PM_at
  • 202338_at
  • 3615713
  • 3772157
  • 3772159
  • 3772160
  • 3772161
  • 3772162
  • 3772163
  • 3772164
  • 3772165
  • 3772166
  • 3772167
  • 3772168
  • 3772169
  • 3772170
  • 3772171
  • 3772172
  • 3772173
  • 3772174
  • 41400_at
  • 7083
  • 8018849
  • 910_at
  • A_23_P107421
  • A_24_P915535
  • GE57538
  • GO:0000166
  • GO:0004797
  • GO:0005515
  • GO:0005524
  • GO:0005634
  • GO:0005737
  • GO:0005829
  • GO:0006139
  • GO:0008270
  • GO:0009157
  • GO:0016301
  • GO:0016740
  • GO:0042802
  • GO:0046104
  • GO:0046105
  • GO:0046872
  • GO:0051289
  • GO:0055086
  • GO:0065003
  • GO:0071897
  • GO:1901135
  • GO:1904860
  • HMNXSV003009883
  • Hs2.105097.2.S1_3p_s_at
  • ILMN_1806037
  • M15205_at
  • PH_hs_0022775
  • PH_hs_0035630
  • TC17001914.hg
  • g4507518_3p_at
  • g4507518_3p_x_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • KITH_HUMAN
  • B2RC58
  • Q969V0
  • Q9UMG9
sequenceLength 234
species [Species:48887] Homo sapiens
stId uniprot:P04183
url http://purl.uniprot.org/uniprot/P04183

Referrals

(referenceEntity)
(interactor)
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