Target Information
| Target General Information | Top | |||||
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| Target ID |
T98089
(Former ID: TTDI01948)
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| Target Name |
Deoxycytidine kinase (DCK)
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| Synonyms |
dCK
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| Gene Name |
DCK
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.1.74
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| Sequence |
MATPPKRSCPSFSASSEGTRIKKISIEGNIAAGKSTFVNILKQLCEDWEVVPEPVARWCN
VQSTQDEFEELTMSQKNGGNVLQMMYEKPERWSFTFQTYACLSRIRAQLASLNGKLKDAE KPVLFFERSVYSDRYIFASNLYESECMNETEWTIYQDWHDWMNNQFGQSLELDGIIYLQA TPETCLHRIYLRGRNEEQGIPLEYLEKLHYKHESWLLHRTLKTNFDYLQEVPILTLDVNE DFKDKYESLVEKVKEFLSTL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T36P6G | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Cytarabine | Ligand Info | |||||
| Structure Description | Structure of human dCK complexed with cytarabine and ADP-MG | PDB:1P5Z | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [2] |
| PDB Sequence |
RIKKISIEGN
29 IAAGKSTFVN39 ILKQLCEDWE49 VVPEPVARWC59 NVQSTNGGNV81 LQMMYEKPER 91 WSFTFQTYAC101 LSRIRAQLAS111 LNGKLKDAEK121 PVLFFERSVY131 SDRYIFASNL 141 YESECMNETE151 WTIYQDWHDW161 MNNQFGQSLE171 LDGIIYLQAT181 PETCLHRIYL 191 RGRNEEQGIP201 LEYLEKLHYK211 HESWLLHRTL221 KTNFDYLQEV231 PILTLDVNED 241 FKDKYESLVE251 KVKEFLSTL
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| Ligand Name: Clofarabine | Ligand Info | |||||
| Structure Description | Crystal structure of human dCK complexed with clofarabine and ADP | PDB:2A7Q | ||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | No | [3] |
| PDB Sequence |
RIKKISIEGN
29 IAAGKSTFVN39 ILKQLCEDWE49 VVPEPVARWC59 NVQSTNGGNV81 LQMMYEKPER 91 WSFTFQTYAC101 LSRIRAQLAS111 LNGKLKDAEK121 PVLFFERSVY131 SDRYIFASNL 141 YESECMNETE151 WTIYQDWHDW161 MNNQFGQSLE171 LDGIIYLQAT181 PETCLHRIYL 191 RGRNEEQGIP201 LEYLEKLHYK211 HESWLLHRTL221 KTNFDYLQEV231 PILTLDVNED 241 FKDKYESLVE251 KVKEFLSTL
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Purine metabolism | hsa00230 | Affiliated Target |
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| Class: Metabolism => Nucleotide metabolism | Pathway Hierarchy | ||
| Pyrimidine metabolism | hsa00240 | Affiliated Target |
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| Class: Metabolism => Nucleotide metabolism | Pathway Hierarchy | ||
| Degree | 7 | Degree centrality | 7.52E-04 | Betweenness centrality | 1.63E-04 |
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| Closeness centrality | 1.66E-01 | Radiality | 1.26E+01 | Clustering coefficient | 1.90E-01 |
| Neighborhood connectivity | 6.43E+00 | Topological coefficient | 1.90E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Drug Resistance Mutation (DRM) | ||||||
| References | Top | |||||
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| REF 1 | 236th ACS National Meeting | |||||
| REF 2 | Structure of human dCK suggests strategies to improve anticancer and antiviral therapy. Nat Struct Biol. 2003 Jul;10(7):513-9. | |||||
| REF 3 | The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation. Acta Crystallogr D Biol Crystallogr. 2006 Feb;62(Pt 2):133-9. | |||||
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