ADK_MOUSE
ID ADK_MOUSE Reviewed; 361 AA.
AC P55264; Q6JAM3; Q91VJ3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Adenosine kinase;
DE Short=AK;
DE EC=2.7.1.20 {ECO:0000269|PubMed:15317590};
DE AltName: Full=Adenosine 5'-phosphotransferase;
GN Name=Adk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP SER-48; SER-85; SER-272 AND SER-328.
RC TISSUE=Brain;
RX PubMed=15317590; DOI=10.1111/j.1432-1033.2004.04291.x;
RA Sahin B., Kansy J.W., Nairn A.C., Spychala J., Ealick S.E., Fienberg A.A.,
RA Greene R.W., Bibb J.A.;
RT "Molecular characterization of recombinant mouse adenosine kinase and
RT evaluation as a target for protein phosphorylation.";
RL Eur. J. Biochem. 271:3547-3555(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 84-361.
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:15317590}.
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:15317590};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20825;
CC Evidence={ECO:0000269|PubMed:15317590};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P55263};
CC Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:P55263};
CC -!- ACTIVITY REGULATION: Activity is inhibited by 5-iodotubercidin and 5'-
CC amino-5'-deoxyadenosine. {ECO:0000250|UniProtKB:P55263}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 1]:
CC Kinetic parameters:
CC KM=20 nM for adenosine {ECO:0000269|PubMed:15317590};
CC Vmax=16 nmol/min/ug enzyme with adenosine as substrat
CC {ECO:0000269|PubMed:15317590};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 2]:
CC Kinetic parameters:
CC KM=20 nM for adenosine {ECO:0000269|PubMed:15317590};
CC Vmax=16 nmol/min/ug enzyme with adenosine as substrat
CC {ECO:0000269|PubMed:15317590};
CC -!- PATHWAY: Purine metabolism; AMP biosynthesis via salvage pathway; AMP
CC from adenosine: step 1/1.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000250|UniProtKB:P55263}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000250|UniProtKB:P55263}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=AK-L {ECO:0000303|PubMed:15317590}, Long;
CC IsoId=P55264-1; Sequence=Displayed;
CC Name=2; Synonyms=AK-S {ECO:0000303|PubMed:15317590}, Short;
CC IsoId=P55264-2; Sequence=VSP_014756;
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:15317590). Highly
CC expressed in liver, testis, kidney and spleen (at protein level). In
CC brain, expression in most forebrain structures and the cerebellum is
CC higher than in the midbrain and brainstem (at protein level)
CC (PubMed:15317590). {ECO:0000269|PubMed:15317590}.
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Major isoform in testis and kidney.
CC Not detected in most brain regions, except in the cerebellum, where it
CC is expressed at a similar level to that of isoform 2 (at protein
CC level). {ECO:0000269|PubMed:15317590}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Major isoform in spleen and in most
CC brain regions, except in the cerebellum, where it is expressed at a
CC similar level to that of isoform 1 (at protein level).
CC {ECO:0000269|PubMed:15317590}.
CC -!- SIMILARITY: Belongs to the carbohydrate kinase PfkB family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA91649.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY540996; AAT07065.1; -; mRNA.
DR EMBL; AY540997; AAT07066.1; -; mRNA.
DR EMBL; BC009659; AAH09659.1; -; mRNA.
DR EMBL; U26589; AAA91649.1; ALT_INIT; mRNA.
DR CCDS; CCDS26862.1; -. [P55264-1]
DR CCDS; CCDS88589.1; -. [P55264-2]
DR RefSeq; NP_001229970.1; NM_001243041.1. [P55264-2]
DR RefSeq; NP_598840.1; NM_134079.4. [P55264-1]
DR PDB; 5KB5; X-ray; 1.80 A; A=20-361.
DR PDB; 5KB6; X-ray; 1.20 A; A/B=1-361.
DR PDBsum; 5KB5; -.
DR PDBsum; 5KB6; -.
DR AlphaFoldDB; P55264; -.
DR SMR; P55264; -.
DR BioGRID; 197988; 2.
DR IntAct; P55264; 2.
DR MINT; P55264; -.
DR STRING; 10090.ENSMUSP00000047665; -.
DR iPTMnet; P55264; -.
DR PhosphoSitePlus; P55264; -.
DR SwissPalm; P55264; -.
DR REPRODUCTION-2DPAGE; P55264; -.
DR EPD; P55264; -.
DR jPOST; P55264; -.
DR MaxQB; P55264; -.
DR PaxDb; P55264; -.
DR PeptideAtlas; P55264; -.
DR PRIDE; P55264; -.
DR ProteomicsDB; 296069; -. [P55264-1]
DR ProteomicsDB; 296070; -. [P55264-2]
DR Antibodypedia; 29612; 463 antibodies from 37 providers.
DR DNASU; 11534; -.
DR Ensembl; ENSMUST00000045376; ENSMUSP00000047665; ENSMUSG00000039197. [P55264-1]
DR Ensembl; ENSMUST00000224069; ENSMUSP00000153089; ENSMUSG00000039197. [P55264-2]
DR GeneID; 11534; -.
DR KEGG; mmu:11534; -.
DR UCSC; uc007sld.2; mouse. [P55264-1]
DR UCSC; uc007sle.2; mouse. [P55264-2]
DR CTD; 132; -.
DR MGI; MGI:87930; Adk.
DR VEuPathDB; HostDB:ENSMUSG00000039197; -.
DR eggNOG; KOG2854; Eukaryota.
DR GeneTree; ENSGT00390000014320; -.
DR HOGENOM; CLU_045832_0_0_1; -.
DR InParanoid; P55264; -.
DR OMA; GGAAMNT; -.
DR PhylomeDB; P55264; -.
DR TreeFam; TF300745; -.
DR BRENDA; 2.7.1.20; 3474.
DR Reactome; R-MMU-74217; Purine salvage.
DR UniPathway; UPA00588; UER00659.
DR BioGRID-ORCS; 11534; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Adk; mouse.
DR PRO; PR:P55264; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P55264; protein.
DR Bgee; ENSMUSG00000039197; Expressed in left lobe of liver and 291 other tissues.
DR ExpressionAtlas; P55264; baseline and differential.
DR Genevisible; P55264; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0004001; F:adenosine kinase activity; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004136; F:deoxyadenosine kinase activity; IMP:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046085; P:adenosine metabolic process; ISO:MGI.
DR GO; GO:0044209; P:AMP salvage; IDA:MGI.
DR GO; GO:0106383; P:dAMP salvage; IMP:MGI.
DR GO; GO:0006175; P:dATP biosynthetic process; IMP:MGI.
DR GO; GO:0032263; P:GMP salvage; IDA:MGI.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISO:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:MGI.
DR GO; GO:0006144; P:purine nucleobase metabolic process; IBA:GO_Central.
DR GO; GO:0006166; P:purine ribonucleoside salvage; IDA:MGI.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; ISO:MGI.
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; Alternative splicing; ATP-binding; Cytoplasm; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Purine salvage; Reference proteome; Transferase.
FT CHAIN 1..361
FT /note="Adenosine kinase"
FT /id="PRO_0000080054"
FT MOTIF 7..15
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P55263"
FT ACT_SITE 316
FT /evidence="ECO:0000250|UniProtKB:P55263"
FT ACT_SITE 316
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P55263"
FT BINDING 34
FT /ligand="adenosine"
FT /ligand_id="ChEBI:CHEBI:16335"
FT /evidence="ECO:0000250|UniProtKB:P55263"
FT BINDING 48
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P55263"
FT BINDING 147
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P55263"
FT BINDING 305
FT /ligand="adenosine"
FT /ligand_id="ChEBI:CHEBI:16335"
FT /evidence="ECO:0000250|UniProtKB:P55263"
FT MOD_RES 76
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P55263"
FT VAR_SEQ 1..20
FT /note="MAAADEPKPKKLKVEAPQAL -> MTST (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15317590"
FT /id="VSP_014756"
FT MUTAGEN 48
FT /note="S->A: No effect on in vitro phosphorylation by PKC."
FT /evidence="ECO:0000269|PubMed:15317590"
FT MUTAGEN 85
FT /note="S->A: No effect on in vitro phosphorylation by PKC."
FT /evidence="ECO:0000269|PubMed:15317590"
FT MUTAGEN 272
FT /note="S->A: No effect on in vitro phosphorylation by PKC."
FT /evidence="ECO:0000269|PubMed:15317590"
FT MUTAGEN 328
FT /note="S->A: No effect on in vitro phosphorylation by PKC."
FT /evidence="ECO:0000269|PubMed:15317590"
FT CONFLICT 92
FT /note="L -> M (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 98
FT /note="K -> R (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 117
FT /note="R -> S (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 155
FT /note="A -> R (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 170
FT /note="R -> N (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="V -> M (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="V -> T (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="D -> A (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 256
FT /note="D -> G (in Ref. 1; AAT07066)"
FT /evidence="ECO:0000305"
FT CONFLICT 262..264
FT /note="KKA -> RKT (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 281
FT /note="T -> RN (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 291..292
FT /note="AE -> TG (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 303
FT /note="Q -> E (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="I -> V (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 314
FT /note="A -> V (in Ref. 1; AAT07066)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="D -> N (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT CONFLICT 359
FT /note="D -> N (in Ref. 3; AAA91649)"
FT /evidence="ECO:0000305"
FT STRAND 25..29
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 32..38
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 41..46
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 64..71
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 81..93
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 100..109
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 110..121
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 125..134
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 138..144
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 147..153
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 155..159
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:5KB6"
FT TURN 165..167
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 169..176
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 179..184
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 185..189
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 192..204
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 208..212
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 216..221
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 223..229
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 230..232
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 234..239
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 240..249
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 257..265
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 277..282
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 285..290
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 295..298
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 305..307
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 314..326
FT /evidence="ECO:0007829|PDB:5KB6"
FT TURN 327..329
FT /evidence="ECO:0007829|PDB:5KB6"
FT HELIX 332..346
FT /evidence="ECO:0007829|PDB:5KB6"
FT STRAND 349..352
FT /evidence="ECO:0007829|PDB:5KB6"
SQ SEQUENCE 361 AA; 40149 MW; 73D5D0451B606757 CRC64;
MAAADEPKPK KLKVEAPQAL SENVLFGMGN PLLDISAVVD KDFLDKYSLK PNDQILAEDK
HKELFDELVK KFKVEYHAGG STQNSMKVAQ WLIQEPHKAA TFFGCIGIDK FGEILKRKAA
DAHVDAHYYE QNEQPTGTCA ACITGGNRSL VANLAAANCY KKEKHLDLER NWVLVEKARV
YYIAGFFLTV SPESVLKVAR YAAENNRVFT LNLSAPFISQ FFKEALMDVM PYVDILFGNE
TEAATFAREQ GFETKDIKEI AKKAQALPKV NSKRQRTVIF TQGRDDTIVA AENDVTAFPV
LDQNQEEIID TNGAGDAFVG GFLSQLVSDK PLTECIRAGH YAASVIIRRT GCTFPEKPDF
H
