Reviewed, UniProtKB/Swiss-Prot P27707 (DCK_HUMAN)

Names and origin

Protein names

Recommended name:
    Deoxycytidine kinase
      Short name=dCK
    EC=2.7.1.74

Gene names

Name:

DCK

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	260 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.
Catalytic activity	NTP + deoxycytidine = NDP + dCMP.
Subunit structure	Homodimer.
Subcellular location	Nucleus. Ref.8
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR By similarity.
Sequence similarities	Belongs to the DCK/DGK family.

Ontologies

Keywords
Cellular component	Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	pyrimidine nucleotide metabolic process Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytosol Inferred from Experiment. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW deoxycytidine kinase activity Ref.1 Traceable author statement. Source: ProtInc phosphotransferase activity, alcohol group as acceptor Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 260

260

Deoxycytidine kinase

PRO_0000175090

Regions

Nucleotide binding

28 – 35

8

ATP Probable

Amino acid modifications

Modified residue

3

1

Phosphothreonine Ref.9

Modified residue

8

1

Phosphoserine Ref.9

Modified residue

11

1

Phosphoserine Ref.9

Modified residue

15

1

Phosphoserine Ref.9

Modified residue

74

1

Phosphoserine Ref.9 Ref.10

Experimental info

Sequence conflict

122

1

P → S in AAV38744. Ref.4

Sequence conflict

122

1

P → S in AAV38745. Ref.4

Secondary structure

1

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260

Helix Strand Turn

Details...

Beta strand

22 – 27

6

Helix

34 – 38

5

Turn

39 – 41

3

Helix

42 – 44

3

Beta strand

48 – 51

4

Helix

55 – 58

4

Helix

81 – 87

7

Helix

89 – 112

24

Helix

115 – 118

4

Beta strand

119 – 121

3

Beta strand

123 – 128

6

Helix

130 – 135

6

Helix

137 – 143

7

Helix

149 – 170

22

Beta strand

173 – 179

7

Helix

182 – 192

11

Helix

195 – 197

3

Helix

202 – 216

15

Helix

226 – 230

5

Beta strand

233 – 237

5

Helix

242 – 258

17

Sequences

	Sequence		Length	Mass (Da)
	P27707-1 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 626B9D2D6BED8DBC	FASTA	260	30,519
	10 20 30 40 50 60 MATPPKRSCP SFSASSEGTR IKKISIEGNI AAGKSTFVNI LKQLCEDWEV VPEPVARWCN 70 80 90 100 110 120 VQSTQDEFEE LTMSQKNGGN VLQMMYEKPE RWSFTFQTYA CLSRIRAQLA SLNGKLKDAE 130 140 150 160 170 180 KPVLFFERSV YSDRYIFASN LYESECMNET EWTIYQDWHD WMNNQFGQSL ELDGIIYLQA 190 200 210 220 230 240 TPETCLHRIY LRGRNEEQGI PLEYLEKLHY KHESWLLHRT LKTNFDYLQE VPILTLDVNE 250 260 DFKDKYESLV EKVKEFLSTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of human deoxycytidine kinase cDNA." Chottiner E.G., Shewach D.S., Datta N.S., Ashcraft E., Gribbin D., Ginsburg D., Fox I.H., Mitchell B.S. Proc. Natl. Acad. Sci. U.S.A. 88:1531-1535(1991) [PubMed: 1996353] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 58-70; 119-127 AND 189-192.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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 T.-O., 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. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Uterus.
[7]	"Characterization of human deoxycytidine kinase. Correlation with cDNA sequences." Eriksson S., Cederlund E., Bergman T., Joernvall H., Bohman C. FEBS Lett. 280:363-366(1991) [PubMed: 2013338] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, CHARACTERIZATION.
[8]	"Human deoxycytidine kinase is located in the cell nucleus." Johansson M., Brismar S., Karlsson A. Proc. Natl. Acad. Sci. U.S.A. 94:11941-11945(1997) [PubMed: 9342341] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3; SER-8; SER-11; SER-15 AND SER-74, MASS SPECTROMETRY.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74, MASS SPECTROMETRY.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[12]	"Structure of human dCK suggests strategies to improve anticancer and antiviral therapy." Sabini E., Ort S., Monnerjahn C., Konrad M., Lavie A. Nat. Struct. Biol. 10:513-519(2003) [PubMed: 12808445] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

IPI

IPI00020454.

PIR

A38585.

RefSeq

NP_000779.1.

UniGene

Hs.709

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1P5Z	X-ray	1.60	B	1-260	[»]
1P60	X-ray	1.96	A/B	1-260	[»]
1P61	X-ray	2.21	B	1-260	[»]
1P62	X-ray	1.90	B	1-260	[»]
2A2Z	X-ray	3.02	A/B/C/D	4-260	[»]
2A30	X-ray	3.02	A/B/C/D	4-260	[»]
2A7Q	X-ray	2.55	A	1-260	[»]
2NO0	X-ray	1.80	A/B	1-260	[»]
2NO1	X-ray	1.91	A/B	1-260	[»]
2NO6	X-ray	1.90	A/B	1-260	[»]
2NO7	X-ray	1.70	A/B	1-260	[»]
2NO9	X-ray	2.15	A/B	1-260	[»]
2NOA	X-ray	1.80	A/B	1-260	[»]
2QRN	X-ray	3.40	A/B/C/D	1-260	[»]
2QRO	X-ray	3.45	A/B/C/D	1-260	[»]
2ZI3	X-ray	2.30	A/B	1-260	[»]
2ZI4	X-ray	2.10	A	1-260	[»]
2ZI5	X-ray	1.77	A/B/C/D	1-260	[»]
2ZI6	X-ray	1.77	A/B/C/D	1-260	[»]
2ZI7	X-ray	1.97	A/B	1-260	[»]
2ZI9	X-ray	2.51	A/B	1-260	[»]
2ZIA	X-ray	1.80	A/B	1-260	[»]
3EXK	X-ray	2.30	A	1-260	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P27707. 4 interactions.

PTM databases

PhosphoSite

P27707.

Proteomic databases

PeptideAtlas

P27707.

PRIDE

P27707.

Genome annotation databases

Ensembl

ENSG00000156136. Homo sapiens. [Contig view]

GeneID

1633.

KEGG

hsa:1633.

UCSC

uc003hfx.1. human.

Organism-specific databases

GeneCards

GC04P072078.

H-InvDB

HIX0031480.

HGNC

HGNC:2704. DCK.

MIM

125450. gene.

PharmGKB

PA137.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P27707.

HOVERGEN

P27707.

OMA

P27707. HRTLKTN.

Enzyme and pathway databases

BRENDA

2.7.1.74. 247.

Reactome

REACT_1698. Metablism of nucleotides.

Gene expression databases

ArrayExpress

P27707.

Bgee

P27707.

CleanEx

HS_DCK.

GermOnline

ENSG00000156136. Homo sapiens.

Family and domain databases

InterPro

IPR002624. Deoxynucleoside_kinase.
[Graphical view]

PANTHER

PTHR10513. dNK. 1 hit.

Pfam

PF01712. dNK. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00242. Cladribine.
DB00631. Clofarabine.
DB01262. Decitabine.
DB01073. Fludarabine.
DB00441. Gemcitabine.
DB00642. Pemetrexed.
DB00943. Zalcitabine.

NextBio

6698.

SOURCE

Search...

Entry information

Entry name

DCK_HUMAN

Accession

Primary (citable) accession number: P27707
Secondary accession number(s): B2R8V6, Q5TZY7, Q6FI11

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	July 7, 2009
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)