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Protein

Deoxyguanosine kinase, mitochondrial

Gene

DGUOK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Phosphorylates deoxyguanosine and deoxyadenosine in the mitochondrial matrix, with the highest efficiency for deoxyguanosine. In non-replicating cells, where cytosolic dNTP synthesis is down-regulated, mtDNA synthesis depends solely on DGUOK and TK2. Phosphorylates certain nucleoside analogs. Widely used as target of antiviral and chemotherapeutic agents.4 Publications

Catalytic activityi

ATP + deoxyguanosine = ADP + dGMP.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei70SubstrateBy similarity1
Binding sitei100Substrate1
Binding sitei111Substrate1
Binding sitei118Substrate1
Active sitei141Proton acceptorSequence analysis1
Binding sitei142Substrate1
Binding sitei147SubstrateBy similarity1
Binding sitei211Substrate1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi45 – 53ATP9
Nucleotide bindingi206 – 208ATP3

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • deoxyguanosine kinase activity Source: UniProtKB
  • deoxynucleoside kinase activity Source: GO_Central
  • nucleoside kinase activity Source: Reactome

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS03819-MONOMER
BRENDAi2.7.1.113 2681
ReactomeiR-HSA-74217 Purine salvage
SABIO-RKiQ16854

Names & Taxonomyi

Protein namesi
Recommended name:
Deoxyguanosine kinase, mitochondrial (EC:2.7.1.113)
Short name:
dGK
Gene namesi
Name:DGUOK
Synonyms:DGK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000114956.19
HGNCiHGNC:2858 DGUOK
MIMi601465 gene
neXtProtiNX_Q16854

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

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Mitochondrial DNA depletion syndrome 3 (MTDPS3)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:251880
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019417142R → K in MTDPS3. 1 PublicationCorresponds to variant dbSNP:rs104893631EnsemblClinVar.1
Natural variantiVAR_019418227E → K in MTDPS3. 1 PublicationCorresponds to variant dbSNP:rs104893632EnsemblClinVar.1
Natural variantiVAR_023789250L → S in MTDPS3; significant reduction of activity. 1 PublicationCorresponds to variant dbSNP:rs749464475EnsemblClinVar.1
Portal hypertension, non-cirrhotic (NCPH)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by portal hypertension associated with hepatosplenomegaly, in absence of cirrhosis, extrahepatic diseases, and splanchnic venous thrombosis. Portal hypertension is defined by a portal venous system pressure that is at least 5 mm Hg higher than the pressure in the inferior vena cava. High pressure in the portal venous system leads to shunting of blood through vessels that are poorly suited to carrying large blood volumes, resulting in collateral circulation and splenomegaly. NCPH patients show normal liver function.
See also OMIM:617068
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07698046N → S in NCPH; impairs adenosine triphosphate binding; reduction of activity. 2 PublicationsCorresponds to variant dbSNP:rs763615602EnsemblClinVar.1
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 (PEOB4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of progressive external ophthalmoplegia, a mitochondrial myopathy characterized by progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. PEOB4 patients manifest clinically variable features including mitochondrial myopathy with or without progressive external ophthalmoplegia, recurrent rhabdomyolysis, and adult-onset lower motor neuron syndrome with mild cognitive impairment.
See also OMIM:617070
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07697944E → K in PEOB4; decreased protein levels. 1 PublicationCorresponds to variant dbSNP:rs762550967EnsemblClinVar.1
Natural variantiVAR_076981154N → K in PEOB4; decreased protein levels. 1 PublicationCorresponds to variant dbSNP:rs144181978EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Neuropathy, Primary mitochondrial disease, Progressive external ophthalmoplegia

Organism-specific databases

DisGeNETi1716
GeneReviewsiDGUOK
MalaCardsiDGUOK
MIMi251880 phenotype
617068 phenotype
617070 phenotype
OpenTargetsiENSG00000114956
Orphaneti329314 Adult-onset multiple mitochondrial DNA deletion syndrome due to DGUOK deficiency
494348 Early-onset familial noncirrhotic portal hypertension
279934 Mitochondrial DNA depletion syndrome, hepatocerebral form due to DGUOK deficiency
PharmGKBiPA27319

Chemistry databases

ChEMBLiCHEMBL5997
DrugBankiDB01280 Nelarabine

Polymorphism and mutation databases

BioMutaiDGUOK
DMDMi23503050

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 39MitochondrionSequence analysisAdd BLAST39
ChainiPRO_000001684040 – 277Deoxyguanosine kinase, mitochondrialAdd BLAST238

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei275N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ16854
MaxQBiQ16854
PaxDbiQ16854
PeptideAtlasiQ16854
PRIDEiQ16854
ProteomicsDBi61106
61107 [Q16854-2]
61108 [Q16854-3]
61109 [Q16854-4]
61110 [Q16854-5]

PTM databases

iPTMnetiQ16854
PhosphoSitePlusiQ16854

Expressioni

Tissue specificityi

Ubiquitous. Highest expression in muscle, brain, liver and lymphoid tissues.1 Publication

Gene expression databases

BgeeiENSG00000114956 Expressed in 232 organ(s), highest expression level in adenohypophysis
CleanExiHS_DGUOK
ExpressionAtlasiQ16854 baseline and differential
GenevisibleiQ16854 HS

Organism-specific databases

HPAiHPA034766
HPA057246

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi108062, 72 interactors
IntActiQ16854, 1 interactor
STRINGi9606.ENSP00000264093

Chemistry databases

BindingDBiQ16854

Structurei

Secondary structure

1277
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ16854
SMRiQ16854
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16854

Family & Domainsi

Sequence similaritiesi

Belongs to the DCK/DGK family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG4235 Eukaryota
COG1428 LUCA
GeneTreeiENSGT00510000046588
HOGENOMiHOG000290165
HOVERGENiHBG006216
InParanoidiQ16854
KOiK00904
OMAiLLDMMYQ
OrthoDBiEOG091G0G7H
PhylomeDBiQ16854
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

Sequences (6)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q16854-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MAAGRLFLSR LRAPFSSMAK SPLEGVSSSR GLHAGRGPRR LSIEGNIAVG
60 70 80 90 100
KSTFVKLLTK TYPEWHVATE PVATWQNIQA AGTQKACTAQ SLGNLLDMMY
110 120 130 140 150
REPARWSYTF QTFSFLSRLK VQLEPFPEKL LQARKPVQIF ERSVYSDRYI
160 170 180 190 200
FAKNLFENGS LSDIEWHIYQ DWHSFLLWEF ASRITLHGFI YLQASPQVCL
210 220 230 240 250
KRLYQRAREE EKGIELAYLE QLHGQHEAWL IHKTTKLHFE ALMNIPVLVL
260 270
DVNDDFSEEV TKQEDLMREV NTFVKNL
Length:277
Mass (Da):32,056
Last modified:September 19, 2002 - v2
Checksum:i53E4514BFC2CB5E5
GO
Isoform 2 (identifier: Q16854-2) [UniParc]FASTAAdd to basket

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

Show »
Length:189
Mass (Da):21,439
Checksum:i0E0CBD1BBBE34002
GO
Isoform 3 (identifier: Q16854-3) [UniParc]FASTAAdd to basket

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

Show »
Length:239
Mass (Da):27,873
Checksum:i786237AC41F6BF66
GO
Isoform 4 (identifier: Q16854-4) [UniParc]FASTAAdd to basket

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

Show »
Length:151
Mass (Da):17,256
Checksum:iAA10F42F818838E5
GO
Isoform 5 (identifier: Q16854-5) [UniParc]FASTAAdd to basket

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

Show »
Length:255
Mass (Da):29,649
Checksum:i24ABF9B977115020
GO
Isoform 6 (identifier: Q16854-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     48-89: AVGKSTFVKL...AAGTQKACTA → GLHCPKSWKL...PPESTAGALP
     90-277: Missing.

Note: No experimental confirmation available.
Show »
Length:89
Mass (Da):9,442
Checksum:i32692C4B9DA9F035
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti83T → N in AAC50624 (PubMed:8692979).Curated1
Sequence conflicti159G → D in CAA66054 (PubMed:8706825).Curated1
Sequence conflicti212K → E in CAA66054 (PubMed:8706825).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07697944E → K in PEOB4; decreased protein levels. 1 PublicationCorresponds to variant dbSNP:rs762550967EnsemblClinVar.1
Natural variantiVAR_07698046N → S in NCPH; impairs adenosine triphosphate binding; reduction of activity. 2 PublicationsCorresponds to variant dbSNP:rs763615602EnsemblClinVar.1
Natural variantiVAR_019417142R → K in MTDPS3. 1 PublicationCorresponds to variant dbSNP:rs104893631EnsemblClinVar.1
Natural variantiVAR_076981154N → K in PEOB4; decreased protein levels. 1 PublicationCorresponds to variant dbSNP:rs144181978EnsemblClinVar.1
Natural variantiVAR_076982170Q → R Unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs74874677EnsemblClinVar.1
Natural variantiVAR_019418227E → K in MTDPS3. 1 PublicationCorresponds to variant dbSNP:rs104893632EnsemblClinVar.1
Natural variantiVAR_023789250L → S in MTDPS3; significant reduction of activity. 1 PublicationCorresponds to variant dbSNP:rs749464475EnsemblClinVar.1
Natural variantiVAR_076983266L → R Reduction of activity. 1 PublicationCorresponds to variant dbSNP:rs886037846EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00302647I → IGNILKQIRGRAPIQET in isoform 5. Curated1
Alternative sequenceiVSP_05602648 – 89AVGKS…KACTA → GLHCPKSWKLAGYDVPGAST MVLHIPDIFLFEPPESTAGA LP in isoform 6. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_00302448 – 85Missing in isoform 3, isoform 4 and isoform 5. CuratedAdd BLAST38
Alternative sequenceiVSP_05602790 – 277Missing in isoform 6. 1 PublicationAdd BLAST188
Alternative sequenceiVSP_003025149 – 236Missing in isoform 2 and isoform 4. CuratedAdd BLAST88

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U41668 mRNA Translation: AAC50624.1
AC073046 Genomic DNA Translation: AAX88910.1
CH471053 Genomic DNA Translation: EAW99704.1
CH471053 Genomic DNA Translation: EAW99707.1
CH471053 Genomic DNA Translation: EAW99709.1
BC015757 mRNA Translation: AAH15757.1
BC024019 mRNA Translation: AAH24019.1
X97386 mRNA Translation: CAA66054.1
U81499 Genomic DNA Translation: AAB39858.1
CCDSiCCDS1931.1 [Q16854-1]
CCDS1932.1 [Q16854-2]
PIRiJC6142
S71315
RefSeqiNP_001305788.1, NM_001318859.1
NP_001305789.1, NM_001318860.1
NP_001305790.1, NM_001318861.1
NP_001305791.1, NM_001318862.1
NP_001305792.1, NM_001318863.1
NP_550438.1, NM_080916.2 [Q16854-1]
NP_550440.1, NM_080918.2 [Q16854-2]
UniGeneiHs.469022

Genome annotation databases

EnsembliENST00000264093; ENSP00000264093; ENSG00000114956 [Q16854-1]
ENST00000348222; ENSP00000306964; ENSG00000114956 [Q16854-2]
ENST00000418996; ENSP00000408209; ENSG00000114956 [Q16854-6]
ENST00000629438; ENSP00000487122; ENSG00000114956 [Q16854-6]
GeneIDi1716
KEGGihsa:1716
UCSCiuc002sjx.3 human [Q16854-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U41668 mRNA Translation: AAC50624.1
AC073046 Genomic DNA Translation: AAX88910.1
CH471053 Genomic DNA Translation: EAW99704.1
CH471053 Genomic DNA Translation: EAW99707.1
CH471053 Genomic DNA Translation: EAW99709.1
BC015757 mRNA Translation: AAH15757.1
BC024019 mRNA Translation: AAH24019.1
X97386 mRNA Translation: CAA66054.1
U81499 Genomic DNA Translation: AAB39858.1
CCDSiCCDS1931.1 [Q16854-1]
CCDS1932.1 [Q16854-2]
PIRiJC6142
S71315
RefSeqiNP_001305788.1, NM_001318859.1
NP_001305789.1, NM_001318860.1
NP_001305790.1, NM_001318861.1
NP_001305791.1, NM_001318862.1
NP_001305792.1, NM_001318863.1
NP_550438.1, NM_080916.2 [Q16854-1]
NP_550440.1, NM_080918.2 [Q16854-2]
UniGeneiHs.469022

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2OCPX-ray2.80A/B/C/D/E/F/G/H37-277[»]
ProteinModelPortaliQ16854
SMRiQ16854
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108062, 72 interactors
IntActiQ16854, 1 interactor
STRINGi9606.ENSP00000264093

Chemistry databases

BindingDBiQ16854
ChEMBLiCHEMBL5997
DrugBankiDB01280 Nelarabine

PTM databases

iPTMnetiQ16854
PhosphoSitePlusiQ16854

Polymorphism and mutation databases

BioMutaiDGUOK
DMDMi23503050

Proteomic databases

EPDiQ16854
MaxQBiQ16854
PaxDbiQ16854
PeptideAtlasiQ16854
PRIDEiQ16854
ProteomicsDBi61106
61107 [Q16854-2]
61108 [Q16854-3]
61109 [Q16854-4]
61110 [Q16854-5]

Protocols and materials databases

DNASUi1716
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264093; ENSP00000264093; ENSG00000114956 [Q16854-1]
ENST00000348222; ENSP00000306964; ENSG00000114956 [Q16854-2]
ENST00000418996; ENSP00000408209; ENSG00000114956 [Q16854-6]
ENST00000629438; ENSP00000487122; ENSG00000114956 [Q16854-6]
GeneIDi1716
KEGGihsa:1716
UCSCiuc002sjx.3 human [Q16854-1]

Organism-specific databases

CTDi1716
DisGeNETi1716
EuPathDBiHostDB:ENSG00000114956.19
GeneCardsiDGUOK
GeneReviewsiDGUOK
HGNCiHGNC:2858 DGUOK
HPAiHPA034766
HPA057246
MalaCardsiDGUOK
MIMi251880 phenotype
601465 gene
617068 phenotype
617070 phenotype
neXtProtiNX_Q16854
OpenTargetsiENSG00000114956
Orphaneti329314 Adult-onset multiple mitochondrial DNA deletion syndrome due to DGUOK deficiency
494348 Early-onset familial noncirrhotic portal hypertension
279934 Mitochondrial DNA depletion syndrome, hepatocerebral form due to DGUOK deficiency
PharmGKBiPA27319
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4235 Eukaryota
COG1428 LUCA
GeneTreeiENSGT00510000046588
HOGENOMiHOG000290165
HOVERGENiHBG006216
InParanoidiQ16854
KOiK00904
OMAiLLDMMYQ
OrthoDBiEOG091G0G7H
PhylomeDBiQ16854
TreeFamiTF324413

Enzyme and pathway databases

BioCyciMetaCyc:HS03819-MONOMER
BRENDAi2.7.1.113 2681
ReactomeiR-HSA-74217 Purine salvage
SABIO-RKiQ16854

Miscellaneous databases

ChiTaRSiDGUOK human
EvolutionaryTraceiQ16854
GeneWikiiDGUOK
GenomeRNAii1716
PROiPR:Q16854
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114956 Expressed in 232 organ(s), highest expression level in adenohypophysis
CleanExiHS_DGUOK
ExpressionAtlasiQ16854 baseline and differential
GenevisibleiQ16854 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 nameiDGUOK_HUMAN
AccessioniPrimary (citable) accession number: Q16854
Secondary accession number(s): P78532
, Q16759, Q4ZG09, Q7L1W9, Q96BC1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 19, 2002
Last modified: November 7, 2018
This is version 177 of the entry and version 2 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, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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