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Q16854 (DGUOK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Deoxyguanosine kinase, mitochondrial

Short name=dGK
EC=2.7.1.113
Gene names
Name:DGUOK
Synonyms:DGK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length277 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3939Mitochondrion Potential
Chain40 – 277238Deoxyguanosine kinase, mitochondrial
PRO_0000016840

Regions

Nucleotide binding45 – 539ATP
Nucleotide binding206 – 2083ATP

Sites

Active site1411Proton acceptor Potential
Binding site701Substrate By similarity
Binding site1001Substrate
Binding site1111Substrate
Binding site1181Substrate
Binding site1421Substrate
Binding site1471Substrate By similarity
Binding site2111Substrate

Amino acid modifications

Modified residue2751N6-acetyllysine Ref.7

Natural variations

Alternative sequence471I → IGNILKQIRGRAPIQET in isoform 5.
VSP_003026
Alternative sequence48 – 8538Missing in isoform 3, isoform 4 and isoform 5.
VSP_003024
Alternative sequence149 – 23688Missing in isoform 2 and isoform 4.
VSP_003025
Natural variant1421R → K in MTDPS3. Ref.9
VAR_019417
Natural variant2271E → K in MTDPS3. Ref.9
VAR_019418
Natural variant2501L → S in MTDPS3; significant reduction of activity. Ref.10
VAR_023789

Experimental info

Sequence conflict831T → N in AAC50624. Ref.1
Sequence conflict1591G → D in CAA66054. Ref.5
Sequence conflict2121K → E in CAA66054. Ref.5

Secondary structure

......................................... 277
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 19, 2002. Version 2.
Checksum: 53E4514BFC2CB5E5

FASTA27732,056
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 0E0CBD1BBBE34002
Show »

FASTA18921,439
Isoform 3 [UniParc].

Checksum: 786237AC41F6BF66
Show »

FASTA23927,873
Isoform 4 [UniParc].

Checksum: AA10F42F818838E5
Show »

FASTA15117,256
Isoform 5 [UniParc].

Checksum: 24ABF9B977115020
Show »

FASTA25529,649

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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

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.
PIRJC6142.
S71315.
RefSeqNP_550438.1. NM_080916.2.
NP_550440.1. NM_080918.2.
UniGeneHs.469022.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2OCPX-ray2.80A/B/C/D/E/F/G/H37-277[»]
ProteinModelPortalQ16854.
SMRQ16854. Positions 37-277.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108062. 6 interactions.
IntActQ16854. 1 interaction.
STRING9606.ENSP00000264093.

Chemistry

BindingDBQ16854.
ChEMBLCHEMBL5997.

PTM databases

PhosphoSiteQ16854.

Polymorphism databases

DMDM23503050.

Proteomic databases

PaxDbQ16854.
PRIDEQ16854.

Protocols and materials databases

DNASU1716.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264093; ENSP00000264093; ENSG00000114956. [Q16854-1]
ENST00000348222; ENSP00000306964; ENSG00000114956. [Q16854-2]
GeneID1716.
KEGGhsa:1716.
UCSCuc002sjx.3. human. [Q16854-1]

Organism-specific databases

CTD1716.
GeneCardsGC02P074153.
HGNCHGNC:2858. DGUOK.
HPAHPA034766.
MIM251880. phenotype.
601465. gene.
neXtProtNX_Q16854.
Orphanet329314. Adult-onset multiple mitochondrial DNA deletion syndrome due to DGUOK deficiency.
279934. Mitochondrial DNA depletion syndrome, hepatocerebral form due to DGUOK deficiency.
PharmGKBPA27319.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1428.
HOGENOMHOG000290165.
HOVERGENHBG006216.
InParanoidQ16854.
KOK00904.
OMALLTKTYP.
OrthoDBEOG70PBZM.
TreeFamTF324413.

Enzyme and pathway databases

BioCycMetaCyc:HS03819-MONOMER.
BRENDA2.7.1.113. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKQ16854.

Gene expression databases

ArrayExpressQ16854.
BgeeQ16854.
CleanExHS_DGUOK.
GenevestigatorQ16854.

Family and domain databases

InterProIPR002624. Deoxynucleoside_kinase.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERPTHR10513. PTHR10513. 1 hit.
PfamPF01712. dNK. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
ProtoNetSearch...

Other

ChiTaRSDGUOK. human.
EvolutionaryTraceQ16854.
GeneWikiDGUOK.
GenomeRNAi1716.
NextBio6950.
PROQ16854.
SOURCESearch...

Entry information

Entry nameDGUOK_HUMAN
AccessionPrimary (citable) accession number: Q16854
Secondary accession number(s): P78532 expand/collapse secondary AC list , Q16759, Q4ZG09, Q96BC1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 19, 2002
Last modified: March 19, 2014
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM