Q16854 (DGUOK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Deoxyguanosine kinase, mitochondrial
Short name=dGK
EC=2.7.1.113

Gene names

Name:	DGUOK
Synonyms:	DGK

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	277 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for the phosphorylation of several deoxyribonucleosides and certain nucleoside analogs widely employed as antiviral and chemotherapeutic agents. Ref.5
Catalytic activity	ATP + deoxyguanosine = ADP + dGMP. Ref.5
Subunit structure	Homodimer. Ref.8
Subcellular location	Mitochondrion.
Tissue specificity	Ubiquitous. Highest expression in muscle, brain, liver and lymphoid tissues. Ref.5
Involvement in disease	Mitochondrial DNA depletion syndrome 3 (MTDPS3) [MIM:251880]: A disorder due to mitochondrial dysfunction characterized by onset in infancy of progressive liver failure, hypoglycemia, increased lactate in body fluids, and neurologic abnormalities including hypotonia, encephalopathy, peripheral neuropathy. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes and mtDNA depletion. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10
Sequence similarities	Belongs to the DCK/DGK family.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Neuropathy
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	dGTP metabolic process Inferred from electronic annotation. Source: Compara guanosine metabolic process Traceable author statement Ref.1. Source: ProtInc negative regulation of neuron projection development Inferred from electronic annotation. Source: Compara protein phosphorylation Inferred from electronic annotation. Source: Compara purine deoxyribonucleoside metabolic process Inferred from direct assay Ref.5. Source: UniProtKB purine nucleobase metabolic process Traceable author statement. Source: Reactome purine-containing compound salvage Traceable author statement. Source: Reactome
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW deoxyguanosine kinase activity Inferred from direct assay Ref.5. Source: UniProtKB phosphotransferase activity, alcohol group as acceptor Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q16854-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q16854-2)

The sequence of this isoform differs from the canonical sequence as follows:
     149-236: Missing.

Isoform 3 (identifier: Q16854-3)

The sequence of this isoform differs from the canonical sequence as follows:
     48-85: Missing.

Isoform 4 (identifier: Q16854-4)

The sequence of this isoform differs from the canonical sequence as follows:
     48-85: Missing.
     149-236: Missing.

Isoform 5 (identifier: Q16854-5)

The sequence of this isoform differs from the canonical sequence as follows:
     47-47: I → IGNILKQIRGRAPIQET
     48-85: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 39

39

Mitochondrion Potential

Chain

40 – 277

238

Deoxyguanosine kinase, mitochondrial

PRO_0000016840

Regions

Nucleotide binding

45 – 53

9

ATP

Nucleotide binding

206 – 208

3

ATP

Sites

Active site

141

1

Proton acceptor Potential

Binding site

70

1

Substrate By similarity

Binding site

100

1

Substrate

Binding site

111

1

Substrate

Binding site

118

1

Substrate

Binding site

142

1

Substrate

Binding site

147

1

Substrate By similarity

Binding site

211

1

Substrate

Amino acid modifications

Modified residue

275

1

N6-acetyllysine Ref.7

Natural variations

Alternative sequence

47

1

I → IGNILKQIRGRAPIQET in isoform 5.

VSP_003026

Alternative sequence

48 – 85

38

Missing in isoform 3, isoform 4 and isoform 5.

VSP_003024

Alternative sequence

149 – 236

88

Missing in isoform 2 and isoform 4.

VSP_003025

Natural variant

142

1

R → K in MTDPS3. Ref.9

VAR_019417

Natural variant

227

1

E → K in MTDPS3. Ref.9

VAR_019418

Natural variant

250

1

L → S in MTDPS3; significant reduction of activity. Ref.10

VAR_023789

Experimental info

Sequence conflict

83

1

T → N in AAC50624. Ref.1

Sequence conflict

159

1

G → D in CAA66054. Ref.5

Sequence conflict

212

1

K → E in CAA66054. Ref.5

Secondary structure

1

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277

Helix Strand Turn

Details...

Beta strand

39 – 45

7

Helix

51 – 61

11

Beta strand

65 – 68

4

Helix

72 – 74

3

Helix

95 – 101

7

Helix

103 – 123

21

Helix

128 – 131

4

Beta strand

137 – 142

6

Helix

144 – 149

6

Helix

151 – 157

7

Helix

163 – 179

17

Helix

181 – 184

4

Beta strand

188 – 193

6

Helix

196 – 205

10

Turn

209 – 213

5

Helix

216 – 230

15

Helix

242 – 244

3

Beta strand

247 – 251

5

Turn

256 – 258

3

Helix

260 – 275

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 19, 2002. Version 2. Checksum: 53E4514BFC2CB5E5	FASTA	277	32,056
	10 20 30 40 50 60 MAAGRLFLSR LRAPFSSMAK SPLEGVSSSR GLHAGRGPRR LSIEGNIAVG KSTFVKLLTK 70 80 90 100 110 120 TYPEWHVATE PVATWQNIQA AGTQKACTAQ SLGNLLDMMY REPARWSYTF QTFSFLSRLK 130 140 150 160 170 180 VQLEPFPEKL LQARKPVQIF ERSVYSDRYI FAKNLFENGS LSDIEWHIYQ DWHSFLLWEF 190 200 210 220 230 240 ASRITLHGFI YLQASPQVCL KRLYQRAREE EKGIELAYLE QLHGQHEAWL IHKTTKLHFE 250 260 270 ALMNIPVLVL DVNDDFSEEV TKQEDLMREV NTFVKNL
	Isoform 2 [UniParc]. Checksum: 0E0CBD1BBBE34002	FASTA	189	21,439
	10 20 30 40 50 60 MAAGRLFLSR LRAPFSSMAK SPLEGVSSSR GLHAGRGPRR LSIEGNIAVG KSTFVKLLTK 70 80 90 100 110 120 TYPEWHVATE PVATWQNIQA AGTQKACTAQ SLGNLLDMMY REPARWSYTF QTFSFLSRLK 130 140 150 160 170 180 VQLEPFPEKL LQARKPVQIF ERSVYSDRLH FEALMNIPVL VLDVNDDFSE EVTKQEDLMR EVNTFVKNL
	Isoform 3 [UniParc]. Checksum: 786237AC41F6BF66	FASTA	239	27,873
	10 20 30 40 50 60 MAAGRLFLSR LRAPFSSMAK SPLEGVSSSR GLHAGRGPRR LSIEGNIACT AQSLGNLLDM 70 80 90 100 110 120 MYREPARWSY TFQTFSFLSR LKVQLEPFPE KLLQARKPVQ IFERSVYSDR YIFAKNLFEN 130 140 150 160 170 180 GSLSDIEWHI YQDWHSFLLW EFASRITLHG FIYLQASPQV CLKRLYQRAR EEEKGIELAY 190 200 210 220 230 LEQLHGQHEA WLIHKTTKLH FEALMNIPVL VLDVNDDFSE EVTKQEDLMR EVNTFVKNL
	Isoform 4 [UniParc]. Checksum: AA10F42F818838E5	FASTA	151	17,256
	10 20 30 40 50 60 MAAGRLFLSR LRAPFSSMAK SPLEGVSSSR GLHAGRGPRR LSIEGNIACT AQSLGNLLDM 70 80 90 100 110 120 MYREPARWSY TFQTFSFLSR LKVQLEPFPE KLLQARKPVQ IFERSVYSDR LHFEALMNIP 130 140 150 VLVLDVNDDF SEEVTKQEDL MREVNTFVKN L
	Isoform 5 [UniParc]. Checksum: 24ABF9B977115020	FASTA	255	29,649
	10 20 30 40 50 60 MAAGRLFLSR LRAPFSSMAK SPLEGVSSSR GLHAGRGPRR LSIEGNIGNI LKQIRGRAPI 70 80 90 100 110 120 QETACTAQSL GNLLDMMYRE PARWSYTFQT FSFLSRLKVQ LEPFPEKLLQ ARKPVQIFER 130 140 150 160 170 180 SVYSDRYIFA KNLFENGSLS DIEWHIYQDW HSFLLWEFAS RITLHGFIYL QASPQVCLKR 190 200 210 220 230 240 LYQRAREEEK GIELAYLEQL HGQHEAWLIH KTTKLHFEAL MNIPVLVLDV NDDFSEEVTK 250 QEDLMREVNT FVKNL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of human deoxyguanosine kinase cDNA." Johansson M., Karlsson A. Proc. Natl. Acad. Sci. U.S.A. 93:7258-7262(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: B-cell.
[5]	"Cloning and expression of human mitochondrial deoxyguanosine kinase cDNA." Wang L., Hellman U., Eriksson S. FEBS Lett. 390:39-43(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 18-277, CATALYTIC ACTIVITY, FUNCTION, TISSUE SPECIFICITY. Tissue: Brain.
[6]	Stegmann A.P.A., Mitchell B.S. Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-47.
[7]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-275, MASS SPECTROMETRY.
[8]	"Structural basis for substrate specificities of cellular deoxyribonucleoside kinases." Johansson K., Ramaswamy S., Ljungcrantz C., Knecht W., Piskur J., Munch-Petersen B., Eriksson S., Eklund H. Nat. Struct. Biol. 8:616-620(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 37-277 IN COMPLEX WITH DEOXYADENOSINE 5'-TRIPHOSPHATE, SUBUNIT.
[9]	"Mitochondrial DNA depletion and dGK gene mutations." Salviati L., Sacconi S., Mancuso M., Otaegui D., Camano P., Marina A., Rabinowitz S., Shiffman R., Thompson K., Wilson C.M., Feigenbaum A., Naini A.B., Hirano M., Bonilla E., DiMauro S., Vu T.H. Ann. Neurol. 52:311-317(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MTDPS3 LYS-142 AND LYS-227.
[10]	"Molecular insight into mitochondrial DNA depletion syndrome in two patients with novel mutations in the deoxyguanosine kinase and thymidine kinase 2 genes." Wang L., Limongelli A., Vila M.R., Carrara F., Zeviani M., Eriksson S. Mol. Genet. Metab. 84:75-82(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MTDPS3 SER-250, CHARACTERIZATION OF VARIANT MTDPS3 SER-250.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U41668 mRNA. Translation: AAC50624.1.
AC073046 Genomic DNA. Translation: AAX88910.1.
CH471053 Genomic DNA. Translation: EAW99709.1.
BC015757 mRNA. Translation: AAH15757.1.
X97386 mRNA. Translation: CAA66054.1.
U81499 Genomic DNA. Translation: AAB39858.1.

IPI

IPI00004461.
IPI00221317.
IPI00221318.
IPI00221319.
IPI00221320.

PIR

JC6142.
S71315.

RefSeq

NP_550438.1. NM_080916.2.
NP_550440.1. NM_080918.2.

UniGene

Hs.469022.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2OCP	X-ray	2.80	A/B/C/D/E/F/G/H	37-277	[»]

ProteinModelPortal

Q16854.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16854. 1 interaction.

STRING

9606.ENSP00000264093.

PTM databases

PhosphoSite

Q16854.

Polymorphism databases

DMDM

23503050.

Proteomic databases

PaxDb

Q16854.

PRIDE

Q16854.

Protocols and materials databases

DNASU

1716.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264093; ENSP00000264093; ENSG00000114956.
ENST00000348222; ENSP00000306964; ENSG00000114956.

GeneID

1716.

KEGG

hsa:1716.

UCSC

uc002sjx.3. human.

Organism-specific databases

CTD

1716.

GeneCards

GC02P074153.

HGNC

HGNC:2858. DGUOK.

HPA

HPA034766.

MIM

251880. phenotype.
601465. gene.

neXtProt

NX_Q16854.

Orphanet

279934. Mitochondrial DNA depletion syndrome, hepatocerebral form due to DGUOK deficiency.

PharmGKB

PA27319.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1428.

HOGENOM

HOG000290165.

HOVERGEN

HBG006216.

InParanoid

Q16854.

KO

K00904.

OMA

KLLTKTY.

OrthoDB

EOG4KKZ3T.

Enzyme and pathway databases

BRENDA

2.7.1.113. 2681.

Reactome

REACT_111217. Metabolism.

SABIO-RK

Q16854.

Gene expression databases

ArrayExpress

Q16854.

Bgee

Q16854.

CleanEx

HS_DGUOK.

Genevestigator

Q16854.

GermOnline

ENSG00000114956. Homo sapiens.

Family and domain databases

InterPro

IPR002624. Deoxynucleoside_kinase.
[Graphical view]

PANTHER

PTHR10513. PTHR10513. 1 hit.

Pfam

PF01712. dNK. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q16854.

ChEMBL

CHEMBL5997.

ChiTaRS

DGUOK. human.

EvolutionaryTrace

Q16854.

GenomeRNAi

1716.

NextBio

6950.

SOURCE

Search...

Entry information

Entry name

DGUOK_HUMAN

Accession

Primary (citable) accession number: Q16854
Secondary accession number(s): P78532 , Q16759, Q4ZG09, Q96BC1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	September 19, 2002
Last modified:	May 1, 2013
This is version 130 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.