DCK_HUMAN
ID DCK_HUMAN Reviewed; 260 AA.
AC P27707; B2R8V6; Q5TZY7; Q6FI11;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Deoxycytidine kinase;
DE Short=dCK;
DE EC=2.7.1.74 {ECO:0000269|PubMed:12808445, ECO:0000269|PubMed:18377927, ECO:0000269|PubMed:19159229, ECO:0000269|PubMed:1996353, ECO:0000269|PubMed:20614893, ECO:0000269|PubMed:20637175};
DE AltName: Full=Deoxyadenosine kinase;
DE EC=2.7.1.76 {ECO:0000269|PubMed:18377927, ECO:0000269|PubMed:19159229, ECO:0000269|PubMed:1996353};
DE AltName: Full=Deoxyguanosine kinase;
DE EC=2.7.1.113 {ECO:0000269|PubMed:19159229, ECO:0000269|PubMed:1996353};
GN Name=DCK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 58-70; 119-127 AND 189-192,
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=1996353; DOI=10.1073/pnas.88.4.1531;
RA Chottiner E.G., Shewach D.S., Datta N.S., Ashcraft E., Gribbin D.,
RA Ginsburg D., Fox I.H., Mitchell B.S.;
RT "Cloning and expression of human deoxycytidine kinase cDNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:1531-1535(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION.
RX PubMed=2013338; DOI=10.1016/0014-5793(91)80332-w;
RA Eriksson S., Cederlund E., Bergman T., Joernvall H., Bohman C.;
RT "Characterization of human deoxycytidine kinase. Correlation with cDNA
RT sequences.";
RL FEBS Lett. 280:363-366(1991).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=9342341; DOI=10.1073/pnas.94.22.11941;
RA Johansson M., Brismar S., Karlsson A.;
RT "Human deoxycytidine kinase is located in the cell nucleus.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:11941-11945(1997).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP PHOSPHORYLATION AT SER-11; SER-15; THR-72 AND SER-74 BY CSNK1D/CK1, AND
RP MUTAGENESIS OF SER-74.
RX PubMed=20637175; DOI=10.1016/j.abb.2010.07.009;
RA Smal C., Vertommen D., Amsailale R., Arts A., Degand H., Morsomme P.,
RA Rider M.H., Neste E.V., Bontemps F.;
RT "Casein kinase 1delta activates human recombinant deoxycytidine kinase by
RT Ser-74 phosphorylation, but is not involved in the in vivo regulation of
RT its activity.";
RL Arch. Biochem. Biophys. 502:44-52(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH ADP; DEOXYCYTIDINE;
RP ARAC AND GEMCITABINE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF ALA-100; ARG-104 AND
RP ASP-133.
RX PubMed=12808445; DOI=10.1038/nsb942;
RA Sabini E., Ort S., Monnerjahn C., Konrad M., Lavie A.;
RT "Structure of human dCK suggests strategies to improve anticancer and
RT antiviral therapy.";
RL Nat. Struct. Biol. 10:513-519(2003).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) IN COMPLEX WITH ADP AND CLOFARABINE,
RP AND SUBUNIT.
RX PubMed=16421443; DOI=10.1107/s0907444905034293;
RA Zhang Y., Secrist J.A. III, Ealick S.E.;
RT "The structure of human deoxycytidine kinase in complex with clofarabine
RT reveals key interactions for prodrug activation.";
RL Acta Crystallogr. D 62:133-139(2006).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEXES WITH ADP;
RP D-DEOXYCYTIDINE; L-DEOXYCYTIDINE AND EMTRICITABINE.
RX PubMed=17530837; DOI=10.1021/jm0700215;
RA Sabini E., Hazra S., Konrad M., Lavie A.;
RT "Nonenantioselectivity property of human deoxycytidine kinase explained by
RT structures of the enzyme in complex with L- and D-nucleosides.";
RL J. Med. Chem. 50:3004-3014(2007).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) IN COMPLEXES WITH D-DEOXYADENOSINE;
RP L-DEOXYADENOSINE; ADP AND UDP, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=18377927; DOI=10.1016/j.jmb.2008.02.061;
RA Sabini E., Hazra S., Ort S., Konrad M., Lavie A.;
RT "Structural basis for substrate promiscuity of dCK.";
RL J. Mol. Biol. 378:607-621(2008).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF ARG-104 AND ASP-133.
RX PubMed=19159229; DOI=10.1021/bi802062w;
RA Hazra S., Sabini E., Ort S., Konrad M., Lavie A.;
RT "Extending thymidine kinase activity to the catalytic repertoire of human
RT deoxycytidine kinase.";
RL Biochemistry 48:1256-1263(2009).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 20-260 IN COMPLEX WITH SYNTHETIC
RP INHIBITOR.
RX PubMed=19836232; DOI=10.1016/j.bmcl.2009.09.081;
RA Jessop T.C., Tarver J.E., Carlsen M., Xu A., Healy J.P., Heim-Riether A.,
RA Fu Q., Taylor J.A., Augeri D.J., Shen M., Stouch T.R., Swanson R.V.,
RA Tari L.W., Hunter M., Hoffman I., Keyes P.E., Yu X.C., Miranda M., Liu Q.,
RA Swaffield J.C., David Kimball S., Nouraldeen A., Wilson A.G., Foushee A.M.,
RA Jhaver K., Finch R., Anderson S., Oravecz T., Carson K.G.;
RT "Lead optimization and structure-based design of potent and bioavailable
RT deoxycytidine kinase inhibitors.";
RL Bioorg. Med. Chem. Lett. 19:6784-6787(2009).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) IN COMPLEX WITH ADP AND
RP 5-METHYL-DEOXYCYTIDINE, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP ARG-104 AND ASP-133.
RX PubMed=20614893; DOI=10.1021/bi100839e;
RA Hazra S., Ort S., Konrad M., Lavie A.;
RT "Structural and kinetic characterization of human deoxycytidine kinase
RT variants able to phosphorylate 5-substituted deoxycytidine and thymidine
RT analogues.";
RL Biochemistry 49:6784-6790(2010).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH ACYCLOVIR AND UDP.
RX PubMed=20684612; DOI=10.1021/jm1005379;
RA Hazra S., Konrad M., Lavie A.;
RT "The sugar ring of the nucleoside is required for productive substrate
RT positioning in the active site of human deoxycytidine kinase (dCK):
RT implications for the development of dCK-activated acyclic guanine
RT analogues.";
RL J. Med. Chem. 53:5792-5800(2010).
CC -!- FUNCTION: Phosphorylates the deoxyribonucleosides deoxycytidine,
CC deoxyguanosine and deoxyadenosine (PubMed:1996353, PubMed:12808445,
CC PubMed:18377927, PubMed:19159229, PubMed:20614893, PubMed:20637175).
CC Has broad substrate specificity, and does not display selectivity based
CC on the chirality of the substrate. It is also an essential enzyme for
CC the phosphorylation of numerous nucleoside analogs widely employed as
CC antiviral and chemotherapeutic agents (PubMed:12808445).
CC {ECO:0000269|PubMed:12808445, ECO:0000269|PubMed:18377927,
CC ECO:0000269|PubMed:19159229, ECO:0000269|PubMed:1996353,
CC ECO:0000269|PubMed:20614893, ECO:0000269|PubMed:20637175}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2'-deoxycytidine + a ribonucleoside 5'-triphosphate = a
CC ribonucleoside 5'-diphosphate + dCMP + H(+); Xref=Rhea:RHEA:20061,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15698, ChEBI:CHEBI:57566,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=2.7.1.74;
CC Evidence={ECO:0000269|PubMed:12808445, ECO:0000269|PubMed:18377927,
CC ECO:0000269|PubMed:19159229, ECO:0000269|PubMed:1996353,
CC ECO:0000269|PubMed:20614893, ECO:0000269|PubMed:20637175};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2'-deoxyadenosine + ATP = ADP + dAMP + H(+);
CC Xref=Rhea:RHEA:23452, ChEBI:CHEBI:15378, ChEBI:CHEBI:17256,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58245, ChEBI:CHEBI:456216;
CC EC=2.7.1.76; Evidence={ECO:0000269|PubMed:18377927,
CC ECO:0000269|PubMed:19159229, ECO:0000269|PubMed:1996353};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2'-deoxyguanosine + ATP = ADP + dGMP + H(+);
CC Xref=Rhea:RHEA:19201, ChEBI:CHEBI:15378, ChEBI:CHEBI:17172,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57673, ChEBI:CHEBI:456216;
CC EC=2.7.1.113; Evidence={ECO:0000269|PubMed:19159229,
CC ECO:0000269|PubMed:1996353};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.2 uM for deoxycytidine (dC) {ECO:0000269|PubMed:12808445};
CC KM=15.5 uM for cytarabine (araC) {ECO:0000269|PubMed:12808445};
CC KM=22 uM for gemcitabine {ECO:0000269|PubMed:12808445};
CC KM=59 nM for deoxycytidine (dC) {ECO:0000269|PubMed:20637175};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12808445,
CC ECO:0000269|PubMed:16421443, ECO:0000269|PubMed:19836232,
CC ECO:0000269|PubMed:20614893, ECO:0000269|PubMed:20684612}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9342341}.
CC -!- PTM: Phosphorylated and activated in vitro upon phosphorylation at Ser-
CC 74 by CSNK1D/CK1. {ECO:0000269|PubMed:20637175}.
CC -!- SIMILARITY: Belongs to the DCK/DGK family. {ECO:0000305}.
CC -!- CAUTION: Was shown to be phosphorylated and activated by CSNK1D/CK1 in
CC vitro but probably not in vivo. {ECO:0000305|PubMed:20637175}.
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DR EMBL; M60527; AAA35752.1; -; mRNA.
DR EMBL; AK313523; BAG36303.1; -; mRNA.
DR EMBL; CR536527; CAG38764.1; -; mRNA.
DR EMBL; CR541876; CAG46674.1; -; mRNA.
DR EMBL; BT019941; AAV38744.1; -; mRNA.
DR EMBL; BT019942; AAV38745.1; -; mRNA.
DR EMBL; CH471057; EAX05637.1; -; Genomic_DNA.
DR EMBL; BC103764; AAI03765.1; -; mRNA.
DR EMBL; BC114617; AAI14618.1; -; mRNA.
DR CCDS; CCDS3548.1; -.
DR PIR; A38585; A38585.
DR RefSeq; NP_000779.1; NM_000788.2.
DR PDB; 1P5Z; X-ray; 1.60 A; B=1-260.
DR PDB; 1P60; X-ray; 1.96 A; A/B=1-260.
DR PDB; 1P61; X-ray; 2.21 A; B=1-260.
DR PDB; 1P62; X-ray; 1.90 A; B=1-260.
DR PDB; 2A2Z; X-ray; 3.02 A; A/B/C/D=1-260.
DR PDB; 2A30; X-ray; 3.02 A; A/B/C/D=1-260.
DR PDB; 2A7Q; X-ray; 2.55 A; A=1-260.
DR PDB; 2NO0; X-ray; 1.80 A; A/B=1-260.
DR PDB; 2NO1; X-ray; 1.91 A; A/B=1-260.
DR PDB; 2NO6; X-ray; 1.90 A; A/B=1-260.
DR PDB; 2NO7; X-ray; 1.70 A; A/B=1-260.
DR PDB; 2NO9; X-ray; 2.15 A; A/B=1-260.
DR PDB; 2NOA; X-ray; 1.80 A; A/B=1-260.
DR PDB; 2QRN; X-ray; 3.40 A; A/B/C/D=1-260.
DR PDB; 2QRO; X-ray; 3.45 A; A/B/C/D=1-260.
DR PDB; 2ZI3; X-ray; 2.30 A; A/B=1-260.
DR PDB; 2ZI4; X-ray; 2.10 A; A=1-260.
DR PDB; 2ZI5; X-ray; 1.77 A; A/B/C/D=1-260.
DR PDB; 2ZI6; X-ray; 1.77 A; A/B/C/D=1-260.
DR PDB; 2ZI7; X-ray; 1.97 A; A/B=1-260.
DR PDB; 2ZI9; X-ray; 2.51 A; A/B=1-260.
DR PDB; 2ZIA; X-ray; 1.80 A; A/B=1-260.
DR PDB; 3HP1; X-ray; 2.31 A; A=1-260.
DR PDB; 3IPX; X-ray; 2.00 A; A=20-260.
DR PDB; 3IPY; X-ray; 2.54 A; A/B=20-260.
DR PDB; 3KFX; X-ray; 1.96 A; A/B=1-260.
DR PDB; 3MJR; X-ray; 2.10 A; A/B/C/D=1-260.
DR PDB; 3QEJ; X-ray; 2.49 A; A/B=1-260.
DR PDB; 3QEN; X-ray; 2.00 A; A/B=1-260.
DR PDB; 3QEO; X-ray; 1.90 A; A/B=1-260.
DR PDB; 4JLJ; X-ray; 2.00 A; A/B=1-260.
DR PDB; 4JLK; X-ray; 1.89 A; A/B=1-260.
DR PDB; 4JLM; X-ray; 2.18 A; A/B=1-260.
DR PDB; 4JLN; X-ray; 2.15 A; A/B=1-260.
DR PDB; 4KCG; X-ray; 2.09 A; A/B=1-260.
DR PDB; 4L5B; X-ray; 1.94 A; A/B=1-260.
DR PDB; 4Q18; X-ray; 2.00 A; A/B=1-260.
DR PDB; 4Q19; X-ray; 2.09 A; A/B=1-260.
DR PDB; 4Q1A; X-ray; 1.90 A; A/B=1-260.
DR PDB; 4Q1B; X-ray; 2.15 A; A/B=1-260.
DR PDB; 4Q1C; X-ray; 2.00 A; A/B=1-260.
DR PDB; 4Q1D; X-ray; 2.00 A; A/B=1-260.
DR PDB; 4Q1E; X-ray; 1.85 A; A/B=1-260.
DR PDB; 4Q1F; X-ray; 2.10 A; A/B=1-260.
DR PDB; 5MQJ; X-ray; 3.70 A; A/B/C/D=2-260.
DR PDB; 5MQL; X-ray; 3.25 A; A/B/C/D=1-260.
DR PDB; 5MQT; X-ray; 3.20 A; A/B/C/D=1-260.
DR PDBsum; 1P5Z; -.
DR PDBsum; 1P60; -.
DR PDBsum; 1P61; -.
DR PDBsum; 1P62; -.
DR PDBsum; 2A2Z; -.
DR PDBsum; 2A30; -.
DR PDBsum; 2A7Q; -.
DR PDBsum; 2NO0; -.
DR PDBsum; 2NO1; -.
DR PDBsum; 2NO6; -.
DR PDBsum; 2NO7; -.
DR PDBsum; 2NO9; -.
DR PDBsum; 2NOA; -.
DR PDBsum; 2QRN; -.
DR PDBsum; 2QRO; -.
DR PDBsum; 2ZI3; -.
DR PDBsum; 2ZI4; -.
DR PDBsum; 2ZI5; -.
DR PDBsum; 2ZI6; -.
DR PDBsum; 2ZI7; -.
DR PDBsum; 2ZI9; -.
DR PDBsum; 2ZIA; -.
DR PDBsum; 3HP1; -.
DR PDBsum; 3IPX; -.
DR PDBsum; 3IPY; -.
DR PDBsum; 3KFX; -.
DR PDBsum; 3MJR; -.
DR PDBsum; 3QEJ; -.
DR PDBsum; 3QEN; -.
DR PDBsum; 3QEO; -.
DR PDBsum; 4JLJ; -.
DR PDBsum; 4JLK; -.
DR PDBsum; 4JLM; -.
DR PDBsum; 4JLN; -.
DR PDBsum; 4KCG; -.
DR PDBsum; 4L5B; -.
DR PDBsum; 4Q18; -.
DR PDBsum; 4Q19; -.
DR PDBsum; 4Q1A; -.
DR PDBsum; 4Q1B; -.
DR PDBsum; 4Q1C; -.
DR PDBsum; 4Q1D; -.
DR PDBsum; 4Q1E; -.
DR PDBsum; 4Q1F; -.
DR PDBsum; 5MQJ; -.
DR PDBsum; 5MQL; -.
DR PDBsum; 5MQT; -.
DR AlphaFoldDB; P27707; -.
DR SMR; P27707; -.
DR BioGRID; 108001; 53.
DR IntAct; P27707; 9.
DR MINT; P27707; -.
DR STRING; 9606.ENSP00000286648; -.
DR BindingDB; P27707; -.
DR ChEMBL; CHEMBL2447; -.
DR DrugBank; DB02594; 2'-Deoxycytidine.
DR DrugBank; DB00242; Cladribine.
DR DrugBank; DB00631; Clofarabine.
DR DrugBank; DB00987; Cytarabine.
DR DrugBank; DB01262; Decitabine.
DR DrugBank; DB05494; Elacytarabine.
DR DrugBank; DB00879; Emtricitabine.
DR DrugBank; DB01073; Fludarabine.
DR DrugBank; DB00441; Gemcitabine.
DR DrugBank; DB00709; Lamivudine.
DR DrugBank; DB01280; Nelarabine.
DR DrugBank; DB00642; Pemetrexed.
DR DrugBank; DB04961; Troxacitabine.
DR DrugBank; DB00943; Zalcitabine.
DR DrugCentral; P27707; -.
DR iPTMnet; P27707; -.
DR PhosphoSitePlus; P27707; -.
DR BioMuta; DCK; -.
DR DMDM; 118447; -.
DR EPD; P27707; -.
DR jPOST; P27707; -.
DR MassIVE; P27707; -.
DR MaxQB; P27707; -.
DR PaxDb; P27707; -.
DR PeptideAtlas; P27707; -.
DR PRIDE; P27707; -.
DR ProteomicsDB; 54408; -.
DR Antibodypedia; 12905; 616 antibodies from 38 providers.
DR DNASU; 1633; -.
DR Ensembl; ENST00000286648.10; ENSP00000286648.5; ENSG00000156136.10.
DR GeneID; 1633; -.
DR KEGG; hsa:1633; -.
DR MANE-Select; ENST00000286648.10; ENSP00000286648.5; NM_000788.3; NP_000779.1.
DR UCSC; uc003hfx.4; human.
DR CTD; 1633; -.
DR DisGeNET; 1633; -.
DR GeneCards; DCK; -.
DR HGNC; HGNC:2704; DCK.
DR HPA; ENSG00000156136; Tissue enhanced (lymphoid).
DR MIM; 125450; gene.
DR neXtProt; NX_P27707; -.
DR OpenTargets; ENSG00000156136; -.
DR PharmGKB; PA137; -.
DR VEuPathDB; HostDB:ENSG00000156136; -.
DR eggNOG; KOG4235; Eukaryota.
DR GeneTree; ENSGT00940000157321; -.
DR HOGENOM; CLU_030466_1_1_1; -.
DR InParanoid; P27707; -.
DR OMA; YQDWHEW; -.
DR OrthoDB; 1505356at2759; -.
DR PhylomeDB; P27707; -.
DR TreeFam; TF324413; -.
DR BioCyc; MetaCyc:HS08100-MON; -.
DR BRENDA; 2.7.1.74; 2681.
DR PathwayCommons; P27707; -.
DR Reactome; R-HSA-73614; Pyrimidine salvage.
DR Reactome; R-HSA-74217; Purine salvage.
DR SABIO-RK; P27707; -.
DR SignaLink; P27707; -.
DR BioGRID-ORCS; 1633; 12 hits in 1079 CRISPR screens.
DR ChiTaRS; DCK; human.
DR EvolutionaryTrace; P27707; -.
DR GeneWiki; Deoxycytidine_kinase; -.
DR GenomeRNAi; 1633; -.
DR Pharos; P27707; Tchem.
DR PRO; PR:P27707; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P27707; protein.
DR Bgee; ENSG00000156136; Expressed in trabecular bone tissue and 200 other tissues.
DR ExpressionAtlas; P27707; baseline and differential.
DR Genevisible; P27707; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043771; F:cytidine kinase activity; IDA:FlyBase.
DR GO; GO:0004136; F:deoxyadenosine kinase activity; IDA:FlyBase.
DR GO; GO:0004137; F:deoxycytidine kinase activity; IDA:UniProtKB.
DR GO; GO:0004138; F:deoxyguanosine kinase activity; IDA:FlyBase.
DR GO; GO:0019136; F:deoxynucleoside kinase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0106383; P:dAMP salvage; IEA:Ensembl.
DR GO; GO:1901293; P:nucleoside phosphate biosynthetic process; IDA:FlyBase.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0006220; P:pyrimidine nucleotide metabolic process; IDA:UniProtKB.
DR CDD; cd01673; dNK; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR002624; DCK/DGK.
DR InterPro; IPR031314; DNK_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF01712; dNK; 1.
DR PIRSF; PIRSF000705; DNK; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Direct protein sequencing; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1..260
FT /note="Deoxycytidine kinase"
FT /id="PRO_0000175090"
FT ACT_SITE 127
FT /note="Proton acceptor"
FT /evidence="ECO:0000255"
FT BINDING 28..36
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 53
FT /ligand="substrate"
FT BINDING 86
FT /ligand="substrate"
FT BINDING 97
FT /ligand="substrate"
FT BINDING 128
FT /ligand="substrate"
FT BINDING 133
FT /ligand="substrate"
FT BINDING 188..192
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 197
FT /ligand="substrate"
FT BINDING 240..242
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 11
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000305|PubMed:20637175"
FT MOD_RES 15
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000305|PubMed:20637175"
FT MOD_RES 72
FT /note="Phosphothreonine; by CK1"
FT /evidence="ECO:0000305|PubMed:20637175"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20637175,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MUTAGEN 74
FT /note="S->A: 4.5-fold increase in Km."
FT /evidence="ECO:0000269|PubMed:20637175"
FT MUTAGEN 100
FT /note="A->V: Strongly increased catalytic efficiency
FT towards deoxycytidine; when associated with M-104 and A-
FT 133."
FT /evidence="ECO:0000269|PubMed:12808445"
FT MUTAGEN 104
FT /note="R->L: Strongly increased catalytic efficiency
FT towards deoxythymidine; when associated with A-133."
FT /evidence="ECO:0000269|PubMed:12808445,
FT ECO:0000269|PubMed:19159229, ECO:0000269|PubMed:20614893"
FT MUTAGEN 104
FT /note="R->M: Strongly increased catalytic efficiency
FT towards deoxycytidine; when associated with V-100 and A-
FT 133."
FT /evidence="ECO:0000269|PubMed:12808445,
FT ECO:0000269|PubMed:19159229, ECO:0000269|PubMed:20614893"
FT MUTAGEN 133
FT /note="D->A: Strongly increased catalytic efficiency
FT towards deoxycytidine; when associated with V-100 and M-
FT 104. Strongly increased catalytic efficiency towards
FT deoxythymidine; when associated with L-104."
FT /evidence="ECO:0000269|PubMed:12808445,
FT ECO:0000269|PubMed:19159229, ECO:0000269|PubMed:20614893"
FT CONFLICT 122
FT /note="P -> S (in Ref. 4; AAV38744/AAV38745)"
FT /evidence="ECO:0000305"
FT STRAND 22..27
FT /evidence="ECO:0007829|PDB:1P5Z"
FT HELIX 34..38
FT /evidence="ECO:0007829|PDB:1P5Z"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:1P5Z"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:1P5Z"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:1P5Z"
FT HELIX 55..58
FT /evidence="ECO:0007829|PDB:1P5Z"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:2A2Z"
FT HELIX 69..72
FT /evidence="ECO:0007829|PDB:2NO7"
FT HELIX 73..77
FT /evidence="ECO:0007829|PDB:2ZI6"
FT HELIX 81..87
FT /evidence="ECO:0007829|PDB:1P5Z"
FT HELIX 89..112
FT /evidence="ECO:0007829|PDB:1P5Z"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:1P5Z"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:1P5Z"
FT STRAND 123..128
FT /evidence="ECO:0007829|PDB:1P5Z"
FT HELIX 130..135
FT /evidence="ECO:0007829|PDB:1P5Z"
FT HELIX 137..143
FT /evidence="ECO:0007829|PDB:1P5Z"
FT HELIX 149..170
FT /evidence="ECO:0007829|PDB:1P5Z"
FT STRAND 173..179
FT /evidence="ECO:0007829|PDB:1P5Z"
FT HELIX 182..192
FT /evidence="ECO:0007829|PDB:1P5Z"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:1P5Z"
FT HELIX 202..216
FT /evidence="ECO:0007829|PDB:1P5Z"
FT HELIX 226..230
FT /evidence="ECO:0007829|PDB:1P5Z"
FT STRAND 233..237
FT /evidence="ECO:0007829|PDB:1P5Z"
FT HELIX 242..258
FT /evidence="ECO:0007829|PDB:1P5Z"
SQ SEQUENCE 260 AA; 30519 MW; 626B9D2D6BED8DBC CRC64;
MATPPKRSCP SFSASSEGTR IKKISIEGNI AAGKSTFVNI LKQLCEDWEV VPEPVARWCN
VQSTQDEFEE LTMSQKNGGN VLQMMYEKPE RWSFTFQTYA CLSRIRAQLA SLNGKLKDAE
KPVLFFERSV YSDRYIFASN LYESECMNET EWTIYQDWHD WMNNQFGQSL ELDGIIYLQA
TPETCLHRIY LRGRNEEQGI PLEYLEKLHY KHESWLLHRT LKTNFDYLQE VPILTLDVNE
DFKDKYESLV EKVKEFLSTL
