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Protein

Deoxycytidine kinase

Gene

DCK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

NTP + deoxycytidine = NDP + dCMP.4 Publications

Kineticsi

  1. KM=6.2 µM for deoxycytidine (dC)1 Publication
  2. KM=15.5 µM for cytarabine (araC)1 Publication
  3. KM=22 µM for gemcitabine (dC)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei53Substrate1
    Binding sitei86Substrate1
    Binding sitei97Substrate1
    Active sitei127Proton acceptorSequence analysis1
    Binding sitei128Substrate1
    Binding sitei133Substrate1
    Binding sitei197Substrate1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi28 – 36ATP9
    Nucleotide bindingi188 – 192ATP5
    Nucleotide bindingi240 – 242ATP3

    GO - Molecular functioni

    • ATP binding Source: UniProtKB-KW
    • deoxycytidine kinase activity Source: UniProtKB
    • drug binding Source: UniProtKB
    • nucleoside kinase activity Source: Reactome
    • protein homodimerization activity Source: UniProtKB

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS08100-MONOMER.
    ZFISH:HS08100-MONOMER.
    BRENDAi2.7.1.74. 2681.
    ReactomeiR-HSA-73614. Pyrimidine salvage reactions.
    R-HSA-74217. Purine salvage.
    SABIO-RKP27707.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Deoxycytidine kinase (EC:2.7.1.74)
    Short name:
    dCK
    Gene namesi
    Name:DCK
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:2704. DCK.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi100A → V: Strongly increased catalytic efficiency towards deoxycytidine; when associated with M-104 and A-133. 1 Publication1
    Mutagenesisi104R → L: Strongly increased catalytic efficiency towards deoxythymidine; when associated with A-133. 3 Publications1
    Mutagenesisi104R → M: Strongly increased catalytic efficiency towards deoxycytidine; when associated with V-100 and A-133. 3 Publications1
    Mutagenesisi133D → A: Strongly increased catalytic efficiency towards deoxycytidine; when associated with V-100 and M-104. Strongly increased catalytic efficiency towards deoxythymidine; when associated with L-104. 3 Publications1

    Organism-specific databases

    DisGeNETi1633.
    OpenTargetsiENSG00000156136.
    PharmGKBiPA137.

    Chemistry databases

    ChEMBLiCHEMBL2447.
    DrugBankiDB00242. Cladribine.
    DB00631. Clofarabine.
    DB00987. Cytarabine.
    DB01262. Decitabine.
    DB00879. Emtricitabine.
    DB01073. Fludarabine.
    DB00441. Gemcitabine.
    DB00709. Lamivudine.
    DB01280. Nelarabine.
    DB00642. Pemetrexed.
    DB00943. Zalcitabine.

    Polymorphism and mutation databases

    BioMutaiDCK.
    DMDMi118447.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001750901 – 260Deoxycytidine kinaseAdd BLAST260

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei11Phosphoserine; by CK11 Publication1
    Modified residuei15Phosphoserine; by CK11 Publication1
    Modified residuei72Phosphothreonine; by CK11 Publication1
    Modified residuei74PhosphoserineCombined sources1 Publication1

    Post-translational modificationi

    Phosphorylated and activated in vitro upon phosphorylation at Ser-74 by CSNK1D/CK1.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiP27707.
    MaxQBiP27707.
    PaxDbiP27707.
    PeptideAtlasiP27707.
    PRIDEiP27707.

    PTM databases

    iPTMnetiP27707.
    PhosphoSitePlusiP27707.

    Expressioni

    Gene expression databases

    BgeeiENSG00000156136.
    CleanExiHS_DCK.
    ExpressionAtlasiP27707. baseline and differential.
    GenevisibleiP27707. HS.

    Organism-specific databases

    HPAiHPA059609.
    HPA062773.

    Interactioni

    Subunit structurei

    Homodimer.5 Publications

    GO - Molecular functioni

    • protein homodimerization activity Source: UniProtKB

    Protein-protein interaction databases

    BioGridi108001. 22 interactors.
    IntActiP27707. 5 interactors.
    MINTiMINT-1387532.
    STRINGi9606.ENSP00000286648.

    Chemistry databases

    BindingDBiP27707.

    Structurei

    Secondary structure

    1260
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi22 – 27Combined sources6
    Helixi34 – 38Combined sources5
    Turni39 – 41Combined sources3
    Helixi42 – 44Combined sources3
    Beta strandi48 – 51Combined sources4
    Helixi55 – 58Combined sources4
    Beta strandi61 – 63Combined sources3
    Helixi69 – 72Combined sources4
    Helixi73 – 77Combined sources5
    Helixi81 – 87Combined sources7
    Helixi89 – 112Combined sources24
    Helixi115 – 118Combined sources4
    Beta strandi119 – 121Combined sources3
    Beta strandi123 – 128Combined sources6
    Helixi130 – 135Combined sources6
    Helixi137 – 143Combined sources7
    Helixi149 – 170Combined sources22
    Beta strandi173 – 179Combined sources7
    Helixi182 – 192Combined sources11
    Helixi195 – 197Combined sources3
    Helixi202 – 216Combined sources15
    Helixi226 – 230Combined sources5
    Beta strandi233 – 237Combined sources5
    Helixi242 – 258Combined sources17

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1P5ZX-ray1.60B1-260[»]
    1P60X-ray1.96A/B1-260[»]
    1P61X-ray2.21B1-260[»]
    1P62X-ray1.90B1-260[»]
    2A2ZX-ray3.02A/B/C/D1-260[»]
    2A30X-ray3.02A/B/C/D1-260[»]
    2A7QX-ray2.55A1-260[»]
    2NO0X-ray1.80A/B1-260[»]
    2NO1X-ray1.91A/B1-260[»]
    2NO6X-ray1.90A/B1-260[»]
    2NO7X-ray1.70A/B1-260[»]
    2NO9X-ray2.15A/B1-260[»]
    2NOAX-ray1.80A/B1-260[»]
    2QRNX-ray3.40A/B/C/D1-260[»]
    2QROX-ray3.45A/B/C/D1-260[»]
    2ZI3X-ray2.30A/B1-260[»]
    2ZI4X-ray2.10A1-260[»]
    2ZI5X-ray1.77A/B/C/D1-260[»]
    2ZI6X-ray1.77A/B/C/D1-260[»]
    2ZI7X-ray1.97A/B1-260[»]
    2ZI9X-ray2.51A/B1-260[»]
    2ZIAX-ray1.80A/B1-260[»]
    3HP1X-ray2.31A1-260[»]
    3IPXX-ray2.00A20-260[»]
    3IPYX-ray2.54A/B20-260[»]
    3KFXX-ray1.96A/B1-260[»]
    3MJRX-ray2.10A/B/C/D1-260[»]
    3QEJX-ray2.49A/B1-260[»]
    3QENX-ray2.00A/B1-260[»]
    3QEOX-ray1.90A/B1-260[»]
    4JLJX-ray2.00A/B1-260[»]
    4JLKX-ray1.89A/B1-260[»]
    4JLMX-ray2.18A/B1-260[»]
    4JLNX-ray2.15A/B1-260[»]
    4KCGX-ray2.09A/B1-260[»]
    4L5BX-ray1.94A/B1-260[»]
    4Q18X-ray2.00A/B1-260[»]
    4Q19X-ray2.09A/B1-260[»]
    4Q1AX-ray1.90A/B1-260[»]
    4Q1BX-ray2.15A/B1-260[»]
    4Q1CX-ray2.00A/B1-260[»]
    4Q1DX-ray2.00A/B1-260[»]
    4Q1EX-ray1.85A/B1-260[»]
    4Q1FX-ray2.10A/B1-260[»]
    ProteinModelPortaliP27707.
    SMRiP27707.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP27707.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the DCK/DGK family.Curated

    Phylogenomic databases

    eggNOGiKOG4235. Eukaryota.
    COG1428. LUCA.
    GeneTreeiENSGT00510000046588.
    HOGENOMiHOG000290165.
    HOVERGENiHBG006216.
    InParanoidiP27707.
    KOiK00893.
    PhylomeDBiP27707.
    TreeFamiTF324413.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    InterProiIPR002624. DCK/DGK.
    IPR031314. DNK_dom.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PfamiPF01712. dNK. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000705. DNK. 1 hit.
    SUPFAMiSSF52540. SSF52540. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P27707-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MATPPKRSCP SFSASSEGTR IKKISIEGNI AAGKSTFVNI LKQLCEDWEV
    60 70 80 90 100
    VPEPVARWCN VQSTQDEFEE LTMSQKNGGN VLQMMYEKPE RWSFTFQTYA
    110 120 130 140 150
    CLSRIRAQLA SLNGKLKDAE KPVLFFERSV YSDRYIFASN LYESECMNET
    160 170 180 190 200
    EWTIYQDWHD WMNNQFGQSL ELDGIIYLQA TPETCLHRIY LRGRNEEQGI
    210 220 230 240 250
    PLEYLEKLHY KHESWLLHRT LKTNFDYLQE VPILTLDVNE DFKDKYESLV
    260
    EKVKEFLSTL
    Length:260
    Mass (Da):30,519
    Last modified:August 1, 1992 - v1
    Checksum:i626B9D2D6BED8DBC
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti122P → S in AAV38744 (Ref. 4) Curated1
    Sequence conflicti122P → S in AAV38745 (Ref. 4) Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M60527 mRNA. Translation: AAA35752.1.
    AK313523 mRNA. Translation: BAG36303.1.
    CR536527 mRNA. Translation: CAG38764.1.
    CR541876 mRNA. Translation: CAG46674.1.
    BT019941 mRNA. Translation: AAV38744.1.
    BT019942 mRNA. Translation: AAV38745.1.
    CH471057 Genomic DNA. Translation: EAX05637.1.
    BC103764 mRNA. Translation: AAI03765.1.
    BC114617 mRNA. Translation: AAI14618.1.
    CCDSiCCDS3548.1.
    PIRiA38585.
    RefSeqiNP_000779.1. NM_000788.2.
    UniGeneiHs.709.

    Genome annotation databases

    EnsembliENST00000286648; ENSP00000286648; ENSG00000156136.
    GeneIDi1633.
    KEGGihsa:1633.
    UCSCiuc003hfx.4. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M60527 mRNA. Translation: AAA35752.1.
    AK313523 mRNA. Translation: BAG36303.1.
    CR536527 mRNA. Translation: CAG38764.1.
    CR541876 mRNA. Translation: CAG46674.1.
    BT019941 mRNA. Translation: AAV38744.1.
    BT019942 mRNA. Translation: AAV38745.1.
    CH471057 Genomic DNA. Translation: EAX05637.1.
    BC103764 mRNA. Translation: AAI03765.1.
    BC114617 mRNA. Translation: AAI14618.1.
    CCDSiCCDS3548.1.
    PIRiA38585.
    RefSeqiNP_000779.1. NM_000788.2.
    UniGeneiHs.709.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1P5ZX-ray1.60B1-260[»]
    1P60X-ray1.96A/B1-260[»]
    1P61X-ray2.21B1-260[»]
    1P62X-ray1.90B1-260[»]
    2A2ZX-ray3.02A/B/C/D1-260[»]
    2A30X-ray3.02A/B/C/D1-260[»]
    2A7QX-ray2.55A1-260[»]
    2NO0X-ray1.80A/B1-260[»]
    2NO1X-ray1.91A/B1-260[»]
    2NO6X-ray1.90A/B1-260[»]
    2NO7X-ray1.70A/B1-260[»]
    2NO9X-ray2.15A/B1-260[»]
    2NOAX-ray1.80A/B1-260[»]
    2QRNX-ray3.40A/B/C/D1-260[»]
    2QROX-ray3.45A/B/C/D1-260[»]
    2ZI3X-ray2.30A/B1-260[»]
    2ZI4X-ray2.10A1-260[»]
    2ZI5X-ray1.77A/B/C/D1-260[»]
    2ZI6X-ray1.77A/B/C/D1-260[»]
    2ZI7X-ray1.97A/B1-260[»]
    2ZI9X-ray2.51A/B1-260[»]
    2ZIAX-ray1.80A/B1-260[»]
    3HP1X-ray2.31A1-260[»]
    3IPXX-ray2.00A20-260[»]
    3IPYX-ray2.54A/B20-260[»]
    3KFXX-ray1.96A/B1-260[»]
    3MJRX-ray2.10A/B/C/D1-260[»]
    3QEJX-ray2.49A/B1-260[»]
    3QENX-ray2.00A/B1-260[»]
    3QEOX-ray1.90A/B1-260[»]
    4JLJX-ray2.00A/B1-260[»]
    4JLKX-ray1.89A/B1-260[»]
    4JLMX-ray2.18A/B1-260[»]
    4JLNX-ray2.15A/B1-260[»]
    4KCGX-ray2.09A/B1-260[»]
    4L5BX-ray1.94A/B1-260[»]
    4Q18X-ray2.00A/B1-260[»]
    4Q19X-ray2.09A/B1-260[»]
    4Q1AX-ray1.90A/B1-260[»]
    4Q1BX-ray2.15A/B1-260[»]
    4Q1CX-ray2.00A/B1-260[»]
    4Q1DX-ray2.00A/B1-260[»]
    4Q1EX-ray1.85A/B1-260[»]
    4Q1FX-ray2.10A/B1-260[»]
    ProteinModelPortaliP27707.
    SMRiP27707.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi108001. 22 interactors.
    IntActiP27707. 5 interactors.
    MINTiMINT-1387532.
    STRINGi9606.ENSP00000286648.

    Chemistry databases

    BindingDBiP27707.
    ChEMBLiCHEMBL2447.
    DrugBankiDB00242. Cladribine.
    DB00631. Clofarabine.
    DB00987. Cytarabine.
    DB01262. Decitabine.
    DB00879. Emtricitabine.
    DB01073. Fludarabine.
    DB00441. Gemcitabine.
    DB00709. Lamivudine.
    DB01280. Nelarabine.
    DB00642. Pemetrexed.
    DB00943. Zalcitabine.

    PTM databases

    iPTMnetiP27707.
    PhosphoSitePlusiP27707.

    Polymorphism and mutation databases

    BioMutaiDCK.
    DMDMi118447.

    Proteomic databases

    EPDiP27707.
    MaxQBiP27707.
    PaxDbiP27707.
    PeptideAtlasiP27707.
    PRIDEiP27707.

    Protocols and materials databases

    DNASUi1633.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000286648; ENSP00000286648; ENSG00000156136.
    GeneIDi1633.
    KEGGihsa:1633.
    UCSCiuc003hfx.4. human.

    Organism-specific databases

    CTDi1633.
    DisGeNETi1633.
    GeneCardsiDCK.
    HGNCiHGNC:2704. DCK.
    HPAiHPA059609.
    HPA062773.
    MIMi125450. gene.
    neXtProtiNX_P27707.
    OpenTargetsiENSG00000156136.
    PharmGKBiPA137.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG4235. Eukaryota.
    COG1428. LUCA.
    GeneTreeiENSGT00510000046588.
    HOGENOMiHOG000290165.
    HOVERGENiHBG006216.
    InParanoidiP27707.
    KOiK00893.
    PhylomeDBiP27707.
    TreeFamiTF324413.

    Enzyme and pathway databases

    BioCyciMetaCyc:HS08100-MONOMER.
    ZFISH:HS08100-MONOMER.
    BRENDAi2.7.1.74. 2681.
    ReactomeiR-HSA-73614. Pyrimidine salvage reactions.
    R-HSA-74217. Purine salvage.
    SABIO-RKP27707.

    Miscellaneous databases

    ChiTaRSiDCK. human.
    EvolutionaryTraceiP27707.
    GeneWikiiDeoxycytidine_kinase.
    GenomeRNAii1633.
    PROiP27707.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000156136.
    CleanExiHS_DCK.
    ExpressionAtlasiP27707. baseline and differential.
    GenevisibleiP27707. HS.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    InterProiIPR002624. DCK/DGK.
    IPR031314. DNK_dom.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PfamiPF01712. dNK. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000705. DNK. 1 hit.
    SUPFAMiSSF52540. SSF52540. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiDCK_HUMAN
    AccessioniPrimary (citable) accession number: P27707
    Secondary accession number(s): B2R8V6, Q5TZY7, Q6FI11
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: August 1, 1992
    Last modified: November 2, 2016
    This is version 157 of the entry and version 1 of the sequence. [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

    Caution

    Was shown to be phosphorylated and activated by CSNK1D/CK1 in vitro but probably not in vivo.1 Publication

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.