Deoxycytidine kinase

Details

Name
Deoxycytidine kinase
Synonyms
  • 2.7.1.74
  • dCK
Gene Name
DCK
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016896|Deoxycytidine kinase
MATPPKRSCPSFSASSEGTRIKKISIEGNIAAGKSTFVNILKQLCEDWEVVPEPVARWCN
VQSTQDEFEELTMSQKNGGNVLQMMYEKPERWSFTFQTYACLSRIRAQLASLNGKLKDAE
KPVLFFERSVYSDRYIFASNLYESECMNETEWTIYQDWHDWMNNQFGQSLELDGIIYLQA
TPETCLHRIYLRGRNEEQGIPLEYLEKLHYKHESWLLHRTLKTNFDYLQEVPILTLDVNE
DFKDKYESLVEKVKEFLSTL
Number of residues
260
Molecular Weight
30518.315
Theoretical pI
4.88
GO Classification
Functions
ATP binding / deoxycytidine kinase activity / drug binding / nucleoside kinase activity / protein homodimerization activity
Processes
deoxyribonucleoside monophosphate biosynthetic process / nucleobase-containing small molecule metabolic process / nucleotide biosynthetic process / purine nucleobase metabolic process / purine-containing compound salvage / pyrimidine nucleobase metabolic process / pyrimidine nucleoside salvage / pyrimidine nucleotide metabolic process / small molecule metabolic process
Components
cytosol / nucleus
General Function
Protein homodimerization activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0016897|Deoxycytidine kinase (DCK)
ATGGCCACCCCGCCCAAGAGAAGCTGCCCGTCTTTCTCAGCCAGCTCTGAGGGGACCCGC
ATCAAGAAAATCTCCATCGAAGGGAACATCGCTGCAGGGAAGTCAACATTTGTGAATATC
CTTAAACAATTGTGTGAAGATTGGGAAGTGGTTCCTGAACCTGTTGCCAGATGGTGCAAT
GTTCAAAGTACTCAAGATGAATTTGAGGAACTTACAATGTCTCAGAAAAATGGTGGGAAT
GTTCTTCAGATGATGTATGAGAAACCTGAACGATGGTCTTTTACCTTCCAAACATATGCC
TGTCTCAGTCGAATAAGAGCTCAGCTTGCCTCTCTGAATGGCAAGCTCAAAGATGCAGAG
AAACCTGTATTATTTTTTGAACGATCTGTGTATAGTGACAGGTATATTTTTGCATCTAAT
TTGTATGAATCTGAATGCATGAATGAGACAGAGTGGACAATTTATCAAGACTGGCATGAC
TGGATGAATAACCAATTTGGCCAAAGCCTTGAATTGGATGGAATCATTTATCTTCAAGCC
ACTCCAGAGACATGCTTACATAGAATATATTTACGGGGAAGAAATGAAGAGCAAGGCATT
CCTCTTGAATATTTAGAGAAGCTTCATTATAAACATGAAAGCTGGCTCCTGCATAGGACA
CTGAAAACCAACTTCGATTATCTTCAAGAGGTGCCTATCTTAACACTGGATGTTAATGAA
GACTTTAAAGACAAATATGAAAGTCTGGTTGAAAAGGTCAAAGAGTTTTTGAGTACTTTG
TGA
Chromosome Location
4
Locus
4q13.3-q21.1
External Identifiers
ResourceLink
UniProtKB IDP27707
UniProtKB Entry NameDCK_HUMAN
GenBank Gene IDM60527
GenAtlas IDDCK
HGNC IDHGNC:2704
General References
  1. Chottiner EG, Shewach DS, Datta NS, Ashcraft E, Gribbin D, Ginsburg D, Fox IH, Mitchell BS: Cloning and expression of human deoxycytidine kinase cDNA. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1531-5. [PubMed:1996353]
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  4. Eriksson S, Cederlund E, Bergman T, Jornvall H, Bohman C: Characterization of human deoxycytidine kinase. Correlation with cDNA sequences. FEBS Lett. 1991 Mar 25;280(2):363-6. [PubMed:2013338]
  5. Johansson M, Brismar S, Karlsson A: Human deoxycytidine kinase is located in the cell nucleus. Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):11941-5. [PubMed:9342341]
  6. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007 May 25;316(5828):1160-6. [PubMed:17525332]
  7. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976]
  8. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648]
  9. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195]
  10. Smal C, Vertommen D, Amsailale R, Arts A, Degand H, Morsomme P, Rider MH, Neste EV, Bontemps F: Casein kinase 1delta activates human recombinant deoxycytidine kinase by Ser-74 phosphorylation, but is not involved in the in vivo regulation of its activity. Arch Biochem Biophys. 2010 Oct 1;502(1):44-52. doi: 10.1016/j.abb.2010.07.009. Epub 2010 Jul 14. [PubMed:20637175]
  11. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [PubMed:20068231]
  12. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  13. Sabini E, Ort S, Monnerjahn C, Konrad M, Lavie A: Structure of human dCK suggests strategies to improve anticancer and antiviral therapy. Nat Struct Biol. 2003 Jul;10(7):513-9. [PubMed:12808445]
  14. Zhang Y, Secrist JA 3rd, Ealick SE: 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. Epub 2006 Jan 18. [PubMed:16421443]
  15. Sabini E, Hazra S, Konrad M, Lavie A: Nonenantioselectivity property of human deoxycytidine kinase explained by structures of the enzyme in complex with L- and D-nucleosides. J Med Chem. 2007 Jun 28;50(13):3004-14. Epub 2007 May 27. [PubMed:17530837]
  16. Sabini E, Hazra S, Ort S, Konrad M, Lavie A: Structural basis for substrate promiscuity of dCK. J Mol Biol. 2008 May 2;378(3):607-21. doi: 10.1016/j.jmb.2008.02.061. Epub 2008 Mar 3. [PubMed:18377927]
  17. Hazra S, Sabini E, Ort S, Konrad M, Lavie A: Extending thymidine kinase activity to the catalytic repertoire of human deoxycytidine kinase. Biochemistry. 2009 Feb 17;48(6):1256-63. doi: 10.1021/bi802062w. [PubMed:19159229]
  18. Jessop TC, Tarver JE, Carlsen M, Xu A, Healy JP, Heim-Riether A, Fu Q, Taylor JA, Augeri DJ, Shen M, Stouch TR, Swanson RV, Tari LW, Hunter M, Hoffman I, Keyes PE, Yu XC, Miranda M, Liu Q, Swaffield JC, David Kimball S, Nouraldeen A, Wilson AG, Foushee AM, Jhaver K, Finch R, Anderson S, Oravecz T, Carson KG: Lead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6784-7. doi: 10.1016/j.bmcl.2009.09.081. Epub 2009 Sep 25. [PubMed:19836232]
  19. Hazra S, Ort S, Konrad M, Lavie A: Structural and kinetic characterization of human deoxycytidine kinase variants able to phosphorylate 5-substituted deoxycytidine and thymidine analogues . Biochemistry. 2010 Aug 10;49(31):6784-90. doi: 10.1021/bi100839e. [PubMed:20614893]
  20. Hazra S, Konrad M, Lavie A: The sugar ring of the nucleoside is required for productive substrate positioning in the active site of human deoxycytidine kinase (dCK): implications for the development of dCK-activated acyclic guanine analogues. J Med Chem. 2010 Aug 12;53(15):5792-800. doi: 10.1021/jm1005379. [PubMed:20684612]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB025942'-Deoxycytidineexperimental, investigationalunknownDetails
DB05494ElacytarabineinvestigationalunknownDetails
DB00242Cladribineapproved, investigationalunknownsubstrateDetails
DB00631Clofarabineapproved, investigationalunknownsubstrateDetails
DB00441GemcitabineapprovedunknownsubstrateDetails
DB00642Pemetrexedapproved, investigationalunknowninducerDetails
DB00943Zalcitabineapproved, investigationalunknownsubstrateDetails
DB01262Decitabineapproved, investigationalyessubstrateDetails
DB025942'-Deoxycytidineexperimental, investigationalunknownsubstrateDetails
DB01280Nelarabineapproved, investigationalunknownsubstrateDetails
DB01073FludarabineapprovedyesagonistDetails
DB00987Cytarabineapproved, investigationalunknownsubstrateDetails
DB00879Emtricitabineapproved, investigationalunknownsubstrateDetails
DB04961TroxacitabineinvestigationalunknownactivatorDetails
DB00709Lamivudineapproved, investigationalunknownsubstrateDetails