ID DGUOK_HUMAN Reviewed; 277 AA. AC Q16854; P78532; Q16759; Q4ZG09; Q96BC1; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 19-SEP-2002, sequence version 2. DT 16-APR-2014, entry version 140. DE RecName: Full=Deoxyguanosine kinase, mitochondrial; DE Short=dGK; DE EC=2.7.1.113; DE Flags: Precursor; GN Name=DGUOK; Synonyms=DGK; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RX PubMed=8692979; DOI=10.1073/pnas.93.14.7258; RA Johansson M., Karlsson A.; RT "Cloning and expression of human deoxyguanosine kinase cDNA."; RL Proc. Natl. Acad. Sci. U.S.A. 93:7258-7262(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=B-cell; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 18-277, CATALYTIC ACTIVITY, FUNCTION, RP AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=8706825; DOI=10.1016/0014-5793(96)00623-0; RA Wang L., Hellman U., Eriksson S.; RT "Cloning and expression of human mitochondrial deoxyguanosine kinase RT cDNA."; RL FEBS Lett. 390:39-43(1996). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-47. RA Stegmann A.P.A., Mitchell B.S.; RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases. RN [7] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-275, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 37-277 IN COMPLEX WITH RP DEOXYADENOSINE 5'-TRIPHOSPHATE, AND SUBUNIT. RX PubMed=11427893; DOI=10.1038/89661; RA Johansson K., Ramaswamy S., Ljungcrantz C., Knecht W., Piskur J., RA Munch-Petersen B., Eriksson S., Eklund H.; RT "Structural basis for substrate specificities of cellular RT deoxyribonucleoside kinases."; RL Nat. Struct. Biol. 8:616-620(2001). RN [9] RP VARIANTS MTDPS3 LYS-142 AND LYS-227. RX PubMed=12205643; DOI=10.1002/ana.10284; RA Salviati L., Sacconi S., Mancuso M., Otaegui D., Camano P., Marina A., RA Rabinowitz S., Shiffman R., Thompson K., Wilson C.M., Feigenbaum A., RA Naini A.B., Hirano M., Bonilla E., DiMauro S., Vu T.H.; RT "Mitochondrial DNA depletion and dGK gene mutations."; RL Ann. Neurol. 52:311-317(2002). RN [10] RP VARIANT MTDPS3 SER-250, AND CHARACTERIZATION OF VARIANT MTDPS3 RP SER-250. RX PubMed=15639197; DOI=10.1016/j.ymgme.2004.09.005; RA Wang L., Limongelli A., Vila M.R., Carrara F., Zeviani M., RA Eriksson S.; RT "Molecular insight into mitochondrial DNA depletion syndrome in two RT patients with novel mutations in the deoxyguanosine kinase and RT thymidine kinase 2 genes."; RL Mol. Genet. Metab. 84:75-82(2005). CC -!- FUNCTION: Required for the phosphorylation of several CC deoxyribonucleosides and certain nucleoside analogs widely CC employed as antiviral and chemotherapeutic agents. CC -!- CATALYTIC ACTIVITY: ATP + deoxyguanosine = ADP + dGMP. CC -!- SUBUNIT: Homodimer. CC -!- SUBCELLULAR LOCATION: Mitochondrion. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=Q16854-1; Sequence=Displayed; CC Name=2; CC IsoId=Q16854-2; Sequence=VSP_003025; CC Name=3; CC IsoId=Q16854-3; Sequence=VSP_003024; CC Name=4; CC IsoId=Q16854-4; Sequence=VSP_003024, VSP_003025; CC Name=5; CC IsoId=Q16854-5; Sequence=VSP_003026, VSP_003024; CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest expression in muscle, CC brain, liver and lymphoid tissues. CC -!- DISEASE: Mitochondrial DNA depletion syndrome 3 (MTDPS3) CC [MIM:251880]: A disorder due to mitochondrial dysfunction CC characterized by onset in infancy of progressive liver failure, CC hypoglycemia, increased lactate in body fluids, and neurologic CC abnormalities including hypotonia, encephalopathy, peripheral CC neuropathy. Affected tissues show both decreased activity of the CC mtDNA-encoded respiratory chain complexes and mtDNA depletion. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the DCK/DGK family. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/books/NBK1116/?term=DGUOK[genesymbol]"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U41668; AAC50624.1; -; mRNA. DR EMBL; AC073046; AAX88910.1; -; Genomic_DNA. DR EMBL; CH471053; EAW99709.1; -; Genomic_DNA. DR EMBL; BC015757; AAH15757.1; -; mRNA. DR EMBL; X97386; CAA66054.1; -; mRNA. DR EMBL; U81499; AAB39858.1; -; Genomic_DNA. DR PIR; JC6142; JC6142. DR PIR; S71315; S71315. DR RefSeq; NP_550438.1; NM_080916.2. DR RefSeq; NP_550440.1; NM_080918.2. DR UniGene; Hs.469022; -. DR PDB; 2OCP; X-ray; 2.80 A; A/B/C/D/E/F/G/H=37-277. DR PDBsum; 2OCP; -. DR ProteinModelPortal; Q16854; -. DR SMR; Q16854; 37-277. DR BioGrid; 108062; 6. DR IntAct; Q16854; 1. DR STRING; 9606.ENSP00000264093; -. DR BindingDB; Q16854; -. DR ChEMBL; CHEMBL5997; -. DR PhosphoSite; Q16854; -. DR DMDM; 23503050; -. DR PaxDb; Q16854; -. DR PRIDE; Q16854; -. DR DNASU; 1716; -. DR Ensembl; ENST00000264093; ENSP00000264093; ENSG00000114956. [Q16854-1] DR Ensembl; ENST00000348222; ENSP00000306964; ENSG00000114956. [Q16854-2] DR GeneID; 1716; -. DR KEGG; hsa:1716; -. DR UCSC; uc002sjx.3; human. [Q16854-1] DR CTD; 1716; -. DR GeneCards; GC02P074153; -. DR HGNC; HGNC:2858; DGUOK. DR HPA; HPA034766; -. DR MIM; 251880; phenotype. DR MIM; 601465; gene. DR neXtProt; NX_Q16854; -. DR Orphanet; 329314; Adult-onset multiple mitochondrial DNA deletion syndrome due to DGUOK deficiency. DR Orphanet; 279934; Mitochondrial DNA depletion syndrome, hepatocerebral form due to DGUOK deficiency. DR PharmGKB; PA27319; -. DR eggNOG; COG1428; -. DR HOGENOM; HOG000290165; -. DR HOVERGEN; HBG006216; -. DR InParanoid; Q16854; -. DR KO; K00904; -. DR OMA; LLTKTYP; -. DR OrthoDB; EOG70PBZM; -. DR PhylomeDB; Q16854; -. DR TreeFam; TF324413; -. DR BioCyc; MetaCyc:HS03819-MONOMER; -. DR BRENDA; 2.7.1.113; 2681. DR Reactome; REACT_111217; Metabolism. DR SABIO-RK; Q16854; -. DR ChiTaRS; DGUOK; human. DR EvolutionaryTrace; Q16854; -. DR GeneWiki; DGUOK; -. DR GenomeRNAi; 1716; -. DR NextBio; 6950; -. DR PRO; PR:Q16854; -. DR ArrayExpress; Q16854; -. DR Bgee; Q16854; -. DR CleanEx; HS_DGUOK; -. DR Genevestigator; Q16854; -. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; TAS:ProtInc. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004138; F:deoxyguanosine kinase activity; IDA:UniProtKB. DR GO; GO:0019206; F:nucleoside kinase activity; EXP:Reactome. DR GO; GO:0016773; F:phosphotransferase activity, alcohol group as acceptor; IEA:InterPro. DR GO; GO:0009157; P:deoxyribonucleoside monophosphate biosynthetic process; IDA:GOC. DR GO; GO:0046070; P:dGTP metabolic process; IEA:Ensembl. DR GO; GO:0008617; P:guanosine metabolic process; TAS:ProtInc. DR GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl. DR GO; GO:0055086; P:nucleobase-containing small molecule metabolic process; TAS:Reactome. DR GO; GO:0009165; P:nucleotide biosynthetic process; EXP:GOC. DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl. DR GO; GO:0046122; P:purine deoxyribonucleoside metabolic process; IDA:UniProtKB. DR GO; GO:0006144; P:purine nucleobase metabolic process; TAS:Reactome. DR GO; GO:0043101; P:purine-containing compound salvage; TAS:Reactome. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR002624; Deoxynucleoside_kinase. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR10513; PTHR10513; 1. DR Pfam; PF01712; dNK; 1. DR SUPFAM; SSF52540; SSF52540; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; KW Complete proteome; Disease mutation; Kinase; Mitochondrion; KW Neuropathy; Nucleotide-binding; Reference proteome; Transferase; KW Transit peptide. FT TRANSIT 1 39 Mitochondrion (Potential). FT CHAIN 40 277 Deoxyguanosine kinase, mitochondrial. FT /FTId=PRO_0000016840. FT NP_BIND 45 53 ATP. FT NP_BIND 206 208 ATP. FT ACT_SITE 141 141 Proton acceptor (Potential). FT BINDING 70 70 Substrate (By similarity). FT BINDING 100 100 Substrate. FT BINDING 111 111 Substrate. FT BINDING 118 118 Substrate. FT BINDING 142 142 Substrate. FT BINDING 147 147 Substrate (By similarity). FT BINDING 211 211 Substrate. FT MOD_RES 275 275 N6-acetyllysine. FT VAR_SEQ 47 47 I -> IGNILKQIRGRAPIQET (in isoform 5). FT /FTId=VSP_003026. FT VAR_SEQ 48 85 Missing (in isoform 3, isoform 4 and FT isoform 5). FT /FTId=VSP_003024. FT VAR_SEQ 149 236 Missing (in isoform 2 and isoform 4). FT /FTId=VSP_003025. FT VARIANT 142 142 R -> K (in MTDPS3). FT /FTId=VAR_019417. FT VARIANT 227 227 E -> K (in MTDPS3). FT /FTId=VAR_019418. FT VARIANT 250 250 L -> S (in MTDPS3; significant reduction FT of activity). FT /FTId=VAR_023789. FT CONFLICT 83 83 T -> N (in Ref. 1; AAC50624). FT CONFLICT 159 159 G -> D (in Ref. 5; CAA66054). FT CONFLICT 212 212 K -> E (in Ref. 5; CAA66054). FT STRAND 39 45 FT HELIX 51 61 FT STRAND 65 68 FT HELIX 72 74 FT HELIX 95 101 FT HELIX 103 123 FT HELIX 128 131 FT STRAND 137 142 FT HELIX 144 149 FT HELIX 151 157 FT HELIX 163 179 FT HELIX 181 184 FT STRAND 188 193 FT HELIX 196 205 FT TURN 209 213 FT HELIX 216 230 FT HELIX 242 244 FT STRAND 247 251 FT TURN 256 258 FT HELIX 260 275 SQ SEQUENCE 277 AA; 32056 MW; 53E4514BFC2CB5E5 CRC64; MAAGRLFLSR LRAPFSSMAK SPLEGVSSSR GLHAGRGPRR LSIEGNIAVG KSTFVKLLTK TYPEWHVATE PVATWQNIQA AGTQKACTAQ SLGNLLDMMY REPARWSYTF QTFSFLSRLK VQLEPFPEKL LQARKPVQIF ERSVYSDRYI FAKNLFENGS LSDIEWHIYQ DWHSFLLWEF ASRITLHGFI YLQASPQVCL KRLYQRAREE EKGIELAYLE QLHGQHEAWL IHKTTKLHFE ALMNIPVLVL DVNDDFSEEV TKQEDLMREV NTFVKNL //