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Protein

Deoxycytidine kinase

Gene

DCK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Caution

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

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
    • deoxynucleoside kinase activity Source: GO_Central
    • drug binding Source: UniProtKB
    • nucleoside kinase activity Source: Reactome
    • protein homodimerization activity Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionKinase, Transferase
    LigandATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS08100-MONOMER
    BRENDAi2.7.1.74 2681
    ReactomeiR-HSA-73614 Pyrimidine salvage
    R-HSA-74217 Purine salvage
    SABIO-RKiP27707

    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

    EuPathDBiHostDB:ENSG00000156136.9
    HGNCiHGNC:2704 DCK
    MIMi125450 gene
    neXtProtiNX_P27707

    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

    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
    DrugBankiDB02594 2'-Deoxycytidine
    DB00242 Cladribine
    DB00631 Clofarabine
    DB05494 CP-4055
    DB00987 Cytarabine
    DB01262 Decitabine
    DB00879 Emtricitabine
    DB01073 Fludarabine
    DB00441 Gemcitabine
    DB00709 Lamivudine
    DB01280 Nelarabine
    DB00642 Pemetrexed
    DB04961 Troxacitabine
    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
    ProteomicsDBi54408

    PTM databases

    iPTMnetiP27707
    PhosphoSitePlusiP27707

    Expressioni

    Gene expression databases

    BgeeiENSG00000156136 Expressed in 225 organ(s), highest expression level in liver
    CleanExiHS_DCK
    ExpressionAtlasiP27707 baseline and differential
    GenevisibleiP27707 HS

    Organism-specific databases

    HPAiHPA059609
    HPA062773

    Interactioni

    Subunit structurei

    Homodimer.5 Publications

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi108001, 26 interactors
    IntActiP27707, 5 interactors
    MINTiP27707
    STRINGi9606.ENSP00000286648

    Chemistry databases

    BindingDBiP27707

    Structurei

    Secondary structure

    1260
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    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

    InterProiView protein in InterPro
    IPR002624 DCK/DGK
    IPR031314 DNK_dom
    IPR027417 P-loop_NTPase
    PfamiView protein in Pfam
    PF01712 dNK, 1 hit
    PIRSFiPIRSF000705 DNK, 1 hit
    SUPFAMiSSF52540 SSF52540, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

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

    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

    Computationally mapped potential isoform sequencesi

    There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    D6RCP9D6RCP9_HUMAN
    Deoxycytidine kinase
    DCK
    199Annotation score:
    D6RFG8D6RFG8_HUMAN
    Deoxycytidine kinase
    DCK
    317Annotation score:
    D6RG38D6RG38_HUMAN
    Deoxycytidine kinase
    DCK
    48Annotation score:
    D6R9C6D6R9C6_HUMAN
    Deoxycytidine kinase
    DCK
    15Annotation score:

    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

    Similar proteinsi

    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[»]
    5MQJX-ray3.70A/B/C/D2-260[»]
    5MQLX-ray3.25A/B/C/D1-260[»]
    5MQTX-ray3.20A/B/C/D1-260[»]
    ProteinModelPortaliP27707
    SMRiP27707
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi108001, 26 interactors
    IntActiP27707, 5 interactors
    MINTiP27707
    STRINGi9606.ENSP00000286648

    Chemistry databases

    BindingDBiP27707
    ChEMBLiCHEMBL2447
    DrugBankiDB02594 2'-Deoxycytidine
    DB00242 Cladribine
    DB00631 Clofarabine
    DB05494 CP-4055
    DB00987 Cytarabine
    DB01262 Decitabine
    DB00879 Emtricitabine
    DB01073 Fludarabine
    DB00441 Gemcitabine
    DB00709 Lamivudine
    DB01280 Nelarabine
    DB00642 Pemetrexed
    DB04961 Troxacitabine
    DB00943 Zalcitabine

    PTM databases

    iPTMnetiP27707
    PhosphoSitePlusiP27707

    Polymorphism and mutation databases

    BioMutaiDCK
    DMDMi118447

    Proteomic databases

    EPDiP27707
    MaxQBiP27707
    PaxDbiP27707
    PeptideAtlasiP27707
    PRIDEiP27707
    ProteomicsDBi54408

    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
    EuPathDBiHostDB:ENSG00000156136.9
    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
    BRENDAi2.7.1.74 2681
    ReactomeiR-HSA-73614 Pyrimidine salvage
    R-HSA-74217 Purine salvage
    SABIO-RKiP27707

    Miscellaneous databases

    ChiTaRSiDCK human
    EvolutionaryTraceiP27707
    GeneWikiiDeoxycytidine_kinase
    GenomeRNAii1633
    PROiPR:P27707
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000156136 Expressed in 225 organ(s), highest expression level in liver
    CleanExiHS_DCK
    ExpressionAtlasiP27707 baseline and differential
    GenevisibleiP27707 HS

    Family and domain databases

    InterProiView protein in InterPro
    IPR002624 DCK/DGK
    IPR031314 DNK_dom
    IPR027417 P-loop_NTPase
    PfamiView protein in Pfam
    PF01712 dNK, 1 hit
    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 historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: August 1, 1992
    Last modified: November 7, 2018
    This is version 168 of the entry and version 1 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, Direct protein sequencing, Reference proteome

    Documents

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

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