ADK_HUMAN
ID ADK_HUMAN Reviewed; 362 AA.
AC P55263; B7Z783; B7Z800; O00741; O00742; Q16710; Q5JQ10; Q5JQ11; Q9BTN2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 213.
DE RecName: Full=Adenosine kinase;
DE Short=AK;
DE EC=2.7.1.20 {ECO:0000269|PubMed:21963049, ECO:0000269|PubMed:8577746, ECO:0000269|PubMed:9070863};
DE AltName: Full=Adenosine 5'-phosphotransferase;
GN Name=ADK {ECO:0000312|HGNC:HGNC:257};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 94-133; 175-200
RP AND 272-289, CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RC TISSUE=Liver;
RX PubMed=8577746; DOI=10.1073/pnas.93.3.1232;
RA Spychala J., Datta N.S., Takabayashi K., Datta M., Fox I.H., Gribbin T.,
RA Mitchell B.S.;
RT "Cloning of human adenosine kinase cDNA: sequence similarity to microbial
RT ribokinases and fructokinases.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:1232-1237(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8917457; DOI=10.1111/j.1432-1033.1996.00564.x;
RA Singh B., Hao W., Wu Z.-C., Eigl B., Gupta R.S.;
RT "Cloning and characterization of cDNA for adenosine kinase from mammalian
RT (Chinese hamster, mouse, human and rat) species. High frequency mutants of
RT Chinese hamster ovary cells involve structural alterations in the gene.";
RL Eur. J. Biochem. 241:564-571(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING,
RP CATALYTIC ACTIVITY, FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP TISSUE SPECIFICITY.
RX PubMed=9070863; DOI=10.1006/bbrc.1997.6157;
RA McNally T., Helfrich R.J., Cowart M., Dorwin S.A., Meuth J.L., Idler K.B.,
RA Klute K.A., Simmer R.L., Kowaluk E.A., Halbert D.N.;
RT "Cloning and expression of the adenosine kinase gene from rat and human
RT tissues.";
RL Biochem. Biophys. Res. Commun. 231:645-650(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
RC TISSUE=Mammary gland, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skin;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), NUCLEAR LOCALIZATION SIGNAL, AND
RP MUTAGENESIS OF 11-LYS-LYS-12.
RX PubMed=19635462; DOI=10.1016/j.bbrc.2009.07.106;
RA Cui X.A., Singh B., Park J., Gupta R.S.;
RT "Subcellular localization of adenosine kinase in mammalian cells: The long
RT isoform of AdK is localized in the nucleus.";
RL Biochem. Biophys. Res. Commun. 388:46-50(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF ISOFORM 2 IN COMPLEX WITH
RP MAGNESIUM AND ADENOSINE.
RX PubMed=9843365; DOI=10.1021/bi9815445;
RA Mathews I.I., Erion M.D., Ealick S.E.;
RT "Structure of human adenosine kinase at 1.5-A resolution.";
RL Biochemistry 37:15607-15620(1998).
RN [14]
RP PHOSPHORYLATION AT TYR-77.
RX PubMed=12112843;
RX DOI=10.1002/1615-9861(200206)2:6<642::aid-prot642>3.0.co;2-i;
RA Maguire P.B., Wynne K.J., Harney D.F., O'Donoghue N.M., Stephens G.,
RA Fitzgerald D.J.;
RT "Identification of the phosphotyrosine proteome from thrombin activated
RT platelets.";
RL Proteomics 2:642-648(2002).
RN [15]
RP VARIANTS HMAKD GLU-30; ALA-235 AND GLU-318, CHARACTERIZATION OF VARIANTS
RP HMAKD GLU-30; ALA-235 AND GLU-318, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=21963049; DOI=10.1016/j.ajhg.2011.09.004;
RA Bjursell M.K., Blom H.J., Cayuela J.A., Engvall M.L., Lesko N.,
RA Balasubramaniam S., Brandberg G., Halldin M., Falkenberg M., Jakobs C.,
RA Smith D., Struys E., von Dobeln U., Gustafsson C.M., Lundeberg J.,
RA Wedell A.;
RT "Adenosine kinase deficiency disrupts the methionine cycle and causes
RT hypermethioninemia, encephalopathy, and abnormal liver function.";
RL Am. J. Hum. Genet. 89:507-515(2011).
CC -!- FUNCTION: Catalyzes the phosphorylation of the purine nucleoside
CC adenosine at the 5' position in an ATP-dependent manner. Serves as a
CC potential regulator of concentrations of extracellular adenosine and
CC intracellular adenine nucleotides. {ECO:0000269|PubMed:21963049,
CC ECO:0000269|PubMed:8577746, ECO:0000269|PubMed:9070863}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine + ATP = ADP + AMP + H(+); Xref=Rhea:RHEA:20824,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16335, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:456215, ChEBI:CHEBI:456216; EC=2.7.1.20;
CC Evidence={ECO:0000269|PubMed:21963049, ECO:0000269|PubMed:8577746,
CC ECO:0000269|PubMed:9070863};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20825;
CC Evidence={ECO:0000305|PubMed:8577746};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:9070863};
CC Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000269|PubMed:9070863};
CC -!- ACTIVITY REGULATION: Activity is inhibited by 5-iodotubercidin and 5'-
CC amino-5'-deoxyadenosine. {ECO:0000269|PubMed:9070863}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 1]:
CC Kinetic parameters:
CC KM=41 nM for adenosine {ECO:0000269|PubMed:8577746};
CC KM=0.13 uM for ATP {ECO:0000269|PubMed:9070863};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 2]:
CC Kinetic parameters:
CC KM=0.12 uM for ATP {ECO:0000269|PubMed:9070863};
CC -!- PATHWAY: Purine metabolism; AMP biosynthesis via salvage pathway; AMP
CC from adenosine: step 1/1.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000269|PubMed:19635462}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:19635462}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=AK-L, Long {ECO:0000303|PubMed:9070863};
CC IsoId=P55263-1; Sequence=Displayed;
CC Name=2; Synonyms=AK-S, Short {ECO:0000303|PubMed:9070863};
CC IsoId=P55263-2; Sequence=VSP_046713;
CC Name=3;
CC IsoId=P55263-3; Sequence=VSP_043526;
CC Name=4;
CC IsoId=P55263-4; Sequence=VSP_004668;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest level in placenta, liver,
CC muscle and kidney. {ECO:0000269|PubMed:9070863}.
CC -!- DISEASE: Hypermethioninemia due to adenosine kinase deficiency (HMAKD)
CC [MIM:614300]: A metabolic disorder characterized by global
CC developmental delay, early-onset seizures, mild dysmorphic features,
CC and characteristic biochemical anomalies, including persistent
CC hypermethioninemia with increased levels of S-adenosylmethionine and S-
CC adenosylhomocysteine. Homocysteine levels are typically normal.
CC {ECO:0000269|PubMed:21963049}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the carbohydrate kinase PfkB family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB01689.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U50196; AAA97893.1; -; mRNA.
DR EMBL; U33936; AAB01689.1; ALT_FRAME; mRNA.
DR EMBL; U90338; AAB50234.1; -; mRNA.
DR EMBL; U90339; AAB50235.1; -; mRNA.
DR EMBL; AK290633; BAF83322.1; -; mRNA.
DR EMBL; AK301590; BAH13519.1; -; mRNA.
DR EMBL; AK302706; BAH13786.1; -; mRNA.
DR EMBL; AC012046; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022026; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022540; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091699; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL357037; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL731576; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54555.1; -; Genomic_DNA.
DR EMBL; CH471083; EAW54556.1; -; Genomic_DNA.
DR EMBL; BC003568; AAH03568.1; -; mRNA.
DR CCDS; CCDS55716.1; -. [P55263-3]
DR CCDS; CCDS55717.1; -. [P55263-4]
DR CCDS; CCDS7343.1; -. [P55263-1]
DR CCDS; CCDS7344.1; -. [P55263-2]
DR PIR; JC5363; JC5363.
DR PIR; JC5364; JC5364.
DR RefSeq; NP_001114.2; NM_001123.3. [P55263-2]
DR RefSeq; NP_001189378.1; NM_001202449.1. [P55263-4]
DR RefSeq; NP_001189379.1; NM_001202450.1. [P55263-3]
DR RefSeq; NP_006712.2; NM_006721.3. [P55263-1]
DR PDB; 1BX4; X-ray; 1.50 A; A=22-362.
DR PDB; 2I6A; X-ray; 2.20 A; A/B/C/D=22-362.
DR PDB; 2I6B; X-ray; 2.30 A; A/B=22-362.
DR PDB; 4O1L; X-ray; 2.50 A; A/B=17-362.
DR PDBsum; 1BX4; -.
DR PDBsum; 2I6A; -.
DR PDBsum; 2I6B; -.
DR PDBsum; 4O1L; -.
DR AlphaFoldDB; P55263; -.
DR SMR; P55263; -.
DR BioGRID; 106644; 41.
DR IntAct; P55263; 6.
DR STRING; 9606.ENSP00000286621; -.
DR BindingDB; P55263; -.
DR ChEMBL; CHEMBL3589; -.
DR DrugBank; DB07280; 5-[4-(DIMETHYLAMINO)PHENYL]-6-[(6-MORPHOLIN-4-YLPYRIDIN-3-YL)ETHYNYL]PYRIMIDIN-4-AMINE.
DR DrugBank; DB07173; 7-(5-DEOXY-BETA-D-RIBOFURANOSYL)-5-IODO-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE.
DR DrugBank; DB01048; Abacavir.
DR DrugBank; DB00640; Adenosine.
DR DrugBank; DB00131; Adenosine phosphate.
DR DrugBank; DB00171; ATP.
DR DrugBank; DB00811; Ribavirin.
DR DrugCentral; P55263; -.
DR GuidetoPHARMACOLOGY; 1231; -.
DR GlyGen; P55263; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P55263; -.
DR MetOSite; P55263; -.
DR PhosphoSitePlus; P55263; -.
DR SwissPalm; P55263; -.
DR BioMuta; ADK; -.
DR DMDM; 6840802; -.
DR REPRODUCTION-2DPAGE; IPI00234368; -.
DR CPTAC; CPTAC-162; -.
DR EPD; P55263; -.
DR jPOST; P55263; -.
DR MassIVE; P55263; -.
DR MaxQB; P55263; -.
DR PaxDb; P55263; -.
DR PeptideAtlas; P55263; -.
DR PRIDE; P55263; -.
DR ProteomicsDB; 56823; -. [P55263-1]
DR ProteomicsDB; 56824; -. [P55263-2]
DR ProteomicsDB; 56825; -. [P55263-3]
DR ProteomicsDB; 6910; -.
DR Antibodypedia; 29612; 463 antibodies from 37 providers.
DR DNASU; 132; -.
DR Ensembl; ENST00000372734.5; ENSP00000361819.3; ENSG00000156110.15. [P55263-2]
DR Ensembl; ENST00000539909.6; ENSP00000443965.2; ENSG00000156110.15. [P55263-1]
DR Ensembl; ENST00000672429.1; ENSP00000500292.1; ENSG00000156110.15. [P55263-3]
DR Ensembl; ENST00000673027.1; ENSP00000500201.1; ENSG00000156110.15. [P55263-4]
DR GeneID; 132; -.
DR KEGG; hsa:132; -.
DR MANE-Select; ENST00000539909.6; ENSP00000443965.2; NM_006721.4; NP_006712.2.
DR UCSC; uc001jwi.4; human. [P55263-1]
DR CTD; 132; -.
DR DisGeNET; 132; -.
DR GeneCards; ADK; -.
DR HGNC; HGNC:257; ADK.
DR HPA; ENSG00000156110; Tissue enhanced (liver).
DR MalaCards; ADK; -.
DR MIM; 102750; gene.
DR MIM; 614300; phenotype.
DR neXtProt; NX_P55263; -.
DR OpenTargets; ENSG00000156110; -.
DR Orphanet; 289290; Hypermethioninemia encephalopathy due to adenosine kinase deficiency.
DR PharmGKB; PA24579; -.
DR VEuPathDB; HostDB:ENSG00000156110; -.
DR eggNOG; KOG2854; Eukaryota.
DR GeneTree; ENSGT00390000014320; -.
DR HOGENOM; CLU_045832_0_0_1; -.
DR InParanoid; P55263; -.
DR OMA; GGAAMNT; -.
DR OrthoDB; 1226324at2759; -.
DR PhylomeDB; P55263; -.
DR TreeFam; TF300745; -.
DR BioCyc; MetaCyc:HS08097-MON; -.
DR BRENDA; 2.7.1.20; 2681.
DR PathwayCommons; P55263; -.
DR Reactome; R-HSA-74217; Purine salvage.
DR SABIO-RK; P55263; -.
DR SignaLink; P55263; -.
DR SIGNOR; P55263; -.
DR UniPathway; UPA00588; UER00659.
DR BioGRID-ORCS; 132; 10 hits in 1087 CRISPR screens.
DR ChiTaRS; ADK; human.
DR EvolutionaryTrace; P55263; -.
DR GeneWiki; ADK_(gene); -.
DR GenomeRNAi; 132; -.
DR Pharos; P55263; Tchem.
DR PRO; PR:P55263; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P55263; protein.
DR Bgee; ENSG00000156110; Expressed in cartilage tissue and 200 other tissues.
DR ExpressionAtlas; P55263; baseline and differential.
DR Genevisible; P55263; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0004001; F:adenosine kinase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004136; F:deoxyadenosine kinase activity; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0044209; P:AMP salvage; IEA:UniProtKB-UniPathway.
DR GO; GO:0106383; P:dAMP salvage; IEA:Ensembl.
DR GO; GO:0006175; P:dATP biosynthetic process; IEA:Ensembl.
DR GO; GO:0032263; P:GMP salvage; IEA:Ensembl.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0006144; P:purine nucleobase metabolic process; IBA:GO_Central.
DR GO; GO:0006166; P:purine ribonucleoside salvage; IEA:UniProtKB-KW.
DR GO; GO:0009156; P:ribonucleoside monophosphate biosynthetic process; TAS:ProtInc.
DR Gene3D; 3.40.1190.20; -; 1.
DR InterPro; IPR001805; Adenokinase.
DR InterPro; IPR002173; Carboh/pur_kinase_PfkB_CS.
DR InterPro; IPR011611; PfkB_dom.
DR InterPro; IPR029056; Ribokinase-like.
DR PANTHER; PTHR45769; PTHR45769; 1.
DR Pfam; PF00294; PfkB; 1.
DR PRINTS; PR00989; ADENOKINASE.
DR SUPFAM; SSF53613; SSF53613; 1.
DR PROSITE; PS00584; PFKB_KINASES_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm;
KW Direct protein sequencing; Disease variant; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Purine salvage;
KW Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..362
FT /note="Adenosine kinase"
FT /id="PRO_0000080053"
FT MOTIF 8..16
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:19635462"
FT ACT_SITE 317
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:9843365,
FT ECO:0007744|PDB:1BX4"
FT BINDING 35
FT /ligand="adenosine"
FT /ligand_id="ChEBI:CHEBI:16335"
FT /evidence="ECO:0000269|PubMed:9843365,
FT ECO:0007744|PDB:1BX4"
FT BINDING 49
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9843365,
FT ECO:0007744|PDB:1BX4"
FT BINDING 147
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9843365,
FT ECO:0007744|PDB:1BX4"
FT BINDING 148
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9843365,
FT ECO:0007744|PDB:1BX4"
FT BINDING 306
FT /ligand="adenosine"
FT /ligand_id="ChEBI:CHEBI:16335"
FT /evidence="ECO:0000269|PubMed:9843365,
FT ECO:0007744|PDB:1BX4"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 77
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12112843"
FT VAR_SEQ 1..65
FT /note="MAAAEEEPKPKKLKVEAPQALRENILFGMGNPLLDISAVVDKDFLDKYSLKP
FT NDQILAEDKHKEL -> MTSVRENILFGMGNPLLDISAVVDKDFLDK (in isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_004668"
FT VAR_SEQ 1..21
FT /note="MAAAEEEPKPKKLKVEAPQAL -> MTSV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8577746,
FT ECO:0000303|PubMed:9070863"
FT /id="VSP_046713"
FT VAR_SEQ 186..242
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043526"
FT VARIANT 30
FT /note="G -> E (in HMAKD; the mutant shows some residual
FT adenosine kinase activity; dbSNP:rs397514454)"
FT /evidence="ECO:0000269|PubMed:21963049"
FT /id="VAR_066640"
FT VARIANT 235
FT /note="D -> A (in HMAKD; the mutant shows some residual
FT adenosine kinase activity; dbSNP:rs397514453)"
FT /evidence="ECO:0000269|PubMed:21963049"
FT /id="VAR_066641"
FT VARIANT 318
FT /note="A -> E (in HMAKD; complete loss of adenosine kinase
FT activity; dbSNP:rs397514452)"
FT /evidence="ECO:0000269|PubMed:21963049"
FT /id="VAR_066642"
FT MUTAGEN 11..12
FT /note="KK->AA,AD: Abolishes nuclear localization."
FT /evidence="ECO:0000269|PubMed:19635462"
FT CONFLICT 98
FT /note="H -> A (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 133
FT /note="N -> D (in Ref. 2; AAB01689)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="K -> R (in Ref. 2; AAB01689)"
FT /evidence="ECO:0000305"
FT CONFLICT 190
FT /note="T -> H (in Ref. 1; AAA97893)"
FT /evidence="ECO:0000305"
FT CONFLICT 219
FT /note="I -> F (in Ref. 7; AAH03568)"
FT /evidence="ECO:0000305"
FT CONFLICT 273
FT /note="S -> V (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 289
FT /note="I -> N (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="K -> R (in Ref. 2; AAB01689)"
FT /evidence="ECO:0000305"
FT STRAND 26..29
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 33..39
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 42..47
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 52..57
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 63..72
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 82..94
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 96..99
FT /evidence="ECO:0007829|PDB:2I6B"
FT STRAND 101..110
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 111..122
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 126..135
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 139..145
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 148..154
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 156..160
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:1BX4"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 170..178
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 180..185
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 186..190
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 193..205
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 209..213
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 217..222
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 224..230
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 235..240
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 241..250
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 258..266
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 278..283
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 286..291
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 296..299
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 312..327
FT /evidence="ECO:0007829|PDB:1BX4"
FT TURN 328..330
FT /evidence="ECO:0007829|PDB:1BX4"
FT HELIX 333..347
FT /evidence="ECO:0007829|PDB:1BX4"
FT STRAND 350..353
FT /evidence="ECO:0007829|PDB:1BX4"
SQ SEQUENCE 362 AA; 40545 MW; 48AA4925865BFE70 CRC64;
MAAAEEEPKP KKLKVEAPQA LRENILFGMG NPLLDISAVV DKDFLDKYSL KPNDQILAED
KHKELFDELV KKFKVEYHAG GSTQNSIKVA QWMIQQPHKA ATFFGCIGID KFGEILKRKA
AEAHVDAHYY EQNEQPTGTC AACITGDNRS LIANLAAANC YKKEKHLDLE KNWMLVEKAR
VCYIAGFFLT VSPESVLKVA HHASENNRIF TLNLSAPFIS QFYKESLMKV MPYVDILFGN
ETEAATFARE QGFETKDIKE IAKKTQALPK MNSKRQRIVI FTQGRDDTIM ATESEVTAFA
VLDQDQKEII DTNGAGDAFV GGFLSQLVSD KPLTECIRAG HYAASIIIRR TGCTFPEKPD
FH
