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Protein

Thymidine kinase, cytosolic

Gene

TK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 activityi

ATP + thymidine = ADP + thymidine 5'-phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei98Proton acceptorSequence analysis1
Binding sitei128Substrate; via amide nitrogenCombined sources4 Publications1
Metal bindingi153ZincCombined sources4 Publications1
Metal bindingi156ZincCombined sources4 Publications1
Binding sitei181SubstrateCombined sources4 Publications1
Metal bindingi185ZincCombined sources4 Publications1
Metal bindingi188ZincCombined sources4 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi26 – 33ATPCombined sources4 Publications8
Nucleotide bindingi58 – 60ATPCombined sources3 Publications3
Nucleotide bindingi97 – 100ATPCombined sources2 Publications4

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • nucleoside kinase activity Source: Reactome
  • thymidine kinase activity Source: GO_Central
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase
Biological processDNA synthesis
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS09657-MONOMER
BRENDAi2.7.1.21 2681
ReactomeiR-HSA-539107 Activation of E2F1 target genes at G1/S
R-HSA-73614 Pyrimidine salvage
SABIO-RKiP04183
SIGNORiP04183

Names & Taxonomyi

Protein namesi
Recommended name:
Thymidine kinase, cytosolic (EC:2.7.1.21)
Gene namesi
Name:TK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000167900.11
HGNCiHGNC:11830 TK1
MIMi188300 gene
neXtProtiNX_P04183

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi163T → S: 140-fold lower K(m) for AZT. 1 Publication1

Organism-specific databases

DisGeNETi7083
OpenTargetsiENSG00000167900
PharmGKBiPA352

Chemistry databases

ChEMBLiCHEMBL2883
DrugBankiDB01692 Dithioerythritol
DB02452 Thymidine-5'-Triphosphate
DB00432 Trifluridine
DB00495 Zidovudine

Polymorphism and mutation databases

BioMutaiTK1
DMDMi23503074

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001749482 – 234Thymidine kinase, cytosolicAdd BLAST233

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei2PhosphoserineCombined sources1
Modified residuei13PhosphoserineCombined sources1 Publication1
Modified residuei231PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on Ser-13 in mitosis.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP04183
MaxQBiP04183
PaxDbiP04183
PeptideAtlasiP04183
PRIDEiP04183
ProteomicsDBi51674

PTM databases

iPTMnetiP04183
PhosphoSitePlusiP04183

Expressioni

Gene expression databases

BgeeiENSG00000167900 Expressed in 146 organ(s), highest expression level in endometrium epithelium
CleanExiHS_TK1
ExpressionAtlasiP04183 baseline and differential
GenevisibleiP04183 HS

Organism-specific databases

HPAiCAB004683

Interactioni

Subunit structurei

Homotetramer.3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112938, 175 interactors
IntActiP04183, 162 interactors
MINTiP04183
STRINGi9606.ENSP00000301634

Chemistry databases

BindingDBiP04183

Structurei

Secondary structure

1234
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP04183
SMRiP04183
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04183

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni172 – 176Substrate bindingCombined sources3 Publications5

Sequence similaritiesi

Belongs to the thymidine kinase family.Curated

Phylogenomic databases

eggNOGiKOG3125 Eukaryota
COG1435 LUCA
GeneTreeiENSGT00390000011309
HOGENOMiHOG000076390
HOVERGENiHBG006215
InParanoidiP04183
KOiK00857
PhylomeDBiP04183
TreeFamiTF314839

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR001267 Thymidine_kinase
IPR020633 Thymidine_kinase_CS
PANTHERiPTHR11441 PTHR11441, 1 hit
PfamiView protein in Pfam
PF00265 TK, 1 hit
PIRSFiPIRSF035805 TK_cell, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00603 TK_CELLULAR_TYPE, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

P04183-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSCINLPTVL PGSPSKTRGQ IQVILGPMFS GKSTELMRRV RRFQIAQYKC
60 70 80 90 100
LVIKYAKDTR YSSSFCTHDR NTMEALPACL LRDVAQEALG VAVIGIDEGQ
110 120 130 140 150
FFPDIVEFCE AMANAGKTVI VAALDGTFQR KPFGAILNLV PLAESVVKLT
160 170 180 190 200
AVCMECFREA AYTKRLGTEK EVEVIGGADK YHSVCRLCYF KKASGQPAGP
210 220 230
DNKENCPVPG KPGEAVAARK LFAPQQILQC SPAN
Length:234
Mass (Da):25,469
Last modified:September 19, 2002 - v2
Checksum:i76901415C631EF21
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7ES52K7ES52_HUMAN
Thymidine kinase
TK1
180Annotation score:
K7ERJ1K7ERJ1_HUMAN
Thymidine kinase
TK1
187Annotation score:
K7ERV3K7ERV3_HUMAN
Thymidine kinase
TK1
267Annotation score:
K7ENW5K7ENW5_HUMAN
Thymidine kinase
TK1
87Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti106V → M in AAA61187 (PubMed:6549046).Curated1
Sequence conflicti106V → M in AAA61191 (PubMed:3301530).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02581 mRNA Translation: AAA61187.1
M15205 Genomic DNA Translation: AAA61191.1
AK314950 mRNA Translation: BAG37455.1
BT006941 mRNA Translation: AAP35587.1
BC006484 mRNA Translation: AAH06484.1
BC007872 mRNA Translation: AAH07872.1
BC007986 mRNA Translation: AAH07986.1
M13643 Genomic DNA Translation: AAA61189.1
CCDSiCCDS11754.1
PIRiA27318 KIHUT
RefSeqiNP_003249.3, NM_003258.4
UniGeneiHs.515122

Genome annotation databases

EnsembliENST00000301634; ENSP00000301634; ENSG00000167900
GeneIDi7083
KEGGihsa:7083
UCSCiuc002juw.3 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02581 mRNA Translation: AAA61187.1
M15205 Genomic DNA Translation: AAA61191.1
AK314950 mRNA Translation: BAG37455.1
BT006941 mRNA Translation: AAP35587.1
BC006484 mRNA Translation: AAH06484.1
BC007872 mRNA Translation: AAH07872.1
BC007986 mRNA Translation: AAH07986.1
M13643 Genomic DNA Translation: AAA61189.1
CCDSiCCDS11754.1
PIRiA27318 KIHUT
RefSeqiNP_003249.3, NM_003258.4
UniGeneiHs.515122

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1W4RX-ray1.83A/B/C/D/E/F/G/H15-194[»]
1XBTX-ray2.40A/B/C/D/E/F/G/H1-193[»]
2ORVX-ray2.30A/B1-234[»]
2WVJX-ray2.20A/B/C/D/E/F/G/H1-193[»]
ProteinModelPortaliP04183
SMRiP04183
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112938, 175 interactors
IntActiP04183, 162 interactors
MINTiP04183
STRINGi9606.ENSP00000301634

Chemistry databases

BindingDBiP04183
ChEMBLiCHEMBL2883
DrugBankiDB01692 Dithioerythritol
DB02452 Thymidine-5'-Triphosphate
DB00432 Trifluridine
DB00495 Zidovudine

PTM databases

iPTMnetiP04183
PhosphoSitePlusiP04183

Polymorphism and mutation databases

BioMutaiTK1
DMDMi23503074

Proteomic databases

EPDiP04183
MaxQBiP04183
PaxDbiP04183
PeptideAtlasiP04183
PRIDEiP04183
ProteomicsDBi51674

Protocols and materials databases

DNASUi7083
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301634; ENSP00000301634; ENSG00000167900
GeneIDi7083
KEGGihsa:7083
UCSCiuc002juw.3 human

Organism-specific databases

CTDi7083
DisGeNETi7083
EuPathDBiHostDB:ENSG00000167900.11
GeneCardsiTK1
HGNCiHGNC:11830 TK1
HPAiCAB004683
MIMi188300 gene
neXtProtiNX_P04183
OpenTargetsiENSG00000167900
PharmGKBiPA352
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3125 Eukaryota
COG1435 LUCA
GeneTreeiENSGT00390000011309
HOGENOMiHOG000076390
HOVERGENiHBG006215
InParanoidiP04183
KOiK00857
PhylomeDBiP04183
TreeFamiTF314839

Enzyme and pathway databases

BioCyciMetaCyc:HS09657-MONOMER
BRENDAi2.7.1.21 2681
ReactomeiR-HSA-539107 Activation of E2F1 target genes at G1/S
R-HSA-73614 Pyrimidine salvage
SABIO-RKiP04183
SIGNORiP04183

Miscellaneous databases

ChiTaRSiTK1 human
EvolutionaryTraceiP04183
GeneWikiiThymidine_kinase_1
GenomeRNAii7083
PROiPR:P04183
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167900 Expressed in 146 organ(s), highest expression level in endometrium epithelium
CleanExiHS_TK1
ExpressionAtlasiP04183 baseline and differential
GenevisibleiP04183 HS

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR001267 Thymidine_kinase
IPR020633 Thymidine_kinase_CS
PANTHERiPTHR11441 PTHR11441, 1 hit
PfamiView protein in Pfam
PF00265 TK, 1 hit
PIRSFiPIRSF035805 TK_cell, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00603 TK_CELLULAR_TYPE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKITH_HUMAN
AccessioniPrimary (citable) accession number: P04183
Secondary accession number(s): B2RC58, Q969V0, Q9UMG9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: September 19, 2002
Last modified: November 7, 2018
This is version 193 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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