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Gene Review

AK1  -  adenylate kinase 1

Homo sapiens

Synonyms: AK 1, ATP-AMP transphosphorylase 1, ATP:AMP phosphotransferase, Adenylate kinase isoenzyme 1, Adenylate monophosphate kinase, ...
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Disease relevance of AK1


Psychiatry related information on AK1


High impact information on AK1

  • Phosphorylation of the glycogen-binding subunit of PP-1G by A-kinase promotes translocation of the catalytic subunit from glycogen particles to cytosol in skeletal muscle, inhibiting the dephosphorylation of glycogen-metabolizing enzymes [9].
  • We found that CFTR also has adenylate kinase activity (ATP + AMP <=> ADP + ADP) that regulates gating [10].
  • An intrinsic adenylate kinase activity regulates gating of the ABC transporter CFTR [10].
  • Thus, channel activity could be regulated by two different enzymatic reactions, ATPase and adenylate kinase, that share a common ATP binding site in the second nucleotide binding domain [10].
  • In eukaryotic cells, most cAMP-inducible genes so far studied are activated by the cAMP-dependent protein kinase (A kinase), which phosphorylates transcription factors that bind the cAMP-responsive element TGACGTCA [11].

Chemical compound and disease context of AK1


Biological context of AK1

  • The AK1 gene frequency was found to be 0.9669 for Caucasians, 0.9813 for Negroes, 0.9779 for Hispanic persons, and 1.000 for Chinese [15].
  • With respect to AK1 phenotypes, there were statistically significant differences between the Central European group on the one hand and the Yemenite and South European groups on the other (p less than 0.05), and with respect to ACP1--between the Middle Eastern and the Yemenite groups (p less than 0.01) [16].
  • The comparisons of amino acid sequences and genomic structure of three isozymes revealed that a segment corresponding to either exon 5 of the AK2 gene or a part of exon 3 of the AK3 gene is missing in the AK1 gene [2].
  • The results of mRNA analysis in various tissues using the AK1 cDNA indicated that the AK1 gene expression is regulated both tissue-specifically and developmentally at the transcriptional level [2].
  • It is probable that AK4 acts on the specific mechanism of energy metabolism rather than control of the homeostasis of the ADP pool ubiquitously [17].

Anatomical context of AK1

  • Western blot analysis of AK isozymes in human heart and skeletal muscle revealed that AK2 protein was found only in heart, whereas AK1 was detected in both tissues [18].
  • The AK1 isoenzyme was partially purified from the cytosol fraction of bovine aortic smooth muscle and had an apparent Mr of 23.5 kilodaltons [19].
  • AK1 is localized in neuronal processes, sperm tail and on the cytoskeleton in cardiac cells at high concentrations, suggesting its regulatory function as a high-energy beta-phosphoryl transfer chain from ATP-synthesizing sites to the ATP-utilizing sites in the cell [20].
  • AK4 mRNA is expressed in the mammalian central nervous system in a region-specific manner from the middle stage of embryogenesis to the adulthood in the rodent [17].
  • The subcellular compartmentalization of the isoenzymes of ATP:AMP phosphotransferase (adenylate kinase) was analyzed in HeLa cells, RAG cells, and RAG-human hybrids that express human AK-2 [21].

Associations of AK1 with chemical compounds

  • Phylogenetic analysis suggested that AK1, a shorter molecule, would have been separated from a longer molecule very early in evolution of adenylate kinase.(ABSTRACT TRUNCATED AT 400 WORDS)[2]
  • In contrast to all other AK isoforms, AMP and dAMP were the preferred substrates of ADLP; CMP, TMP and shikimate acid were also good substrates [22].
  • Enzymatic characterization by hemolysate revealed that the patient's AK had an increased Michaelis constant for adenosine diphosphate and slight thermal instability [1].
  • Adenylate kinase is an ubiquitous enzyme which contributes to homeostasis of adenine nucleotide composition in the cell [2].
  • The residual activity was not inhibited by N-ethylmaleimide, which completely abolishes the activity of the normal AK1 isozyme of erythrocytes [23].

Physical interactions of AK1


Regulatory relationships of AK1

  • In addition, AK-1 was found to be expressed independently of AK-2 [26].
  • We hypothesize that during periods of high energy demand, exclusively AMP deaminase is activated as a means (1) to push the myokinase reaction toward ATP synthesis, (2) to supply allosteric effectors, and (3) to remove some of the accumulating protons through the formation of ammonium, all at the expense of the adenylate pool [27].

Other interactions of AK1

  • Subcellular localization studies showed a predominant nuclear localization for this protein, which is different from AK1-AK5, but similar to that of human AK6 [22].
  • Cloning and expression of human adenylate kinase 2 isozymes: differential expression of adenylate kinase 1 and 2 in human muscle tissues [18].
  • The gene frequencies observed are: PGM1/1: 0.715, AK1: 0.962 AND ADA1: 0.940 [28].
  • The ADA, PGM and AK enzymes were found to be polymorphic in the Turkish population [29].
  • The interpopulation heterogeneity test shows a high level of genetic differentiation in the following loci: HP, GC, ESD, AK1, TF, PGD [30].

Analytical, diagnostic and therapeutic context of AK1

  • The patient's enzyme migrated approximately half-way between the AK 1 and AK 2 position on starch-gel electrophoresis [1].
  • The adenylate kinase zymograms obtained from isoelectric focusing yielded two typical isoform patterns: (1) with a pI greater than or equal to 9 and 8.6, specific for bovine skeletal muscle, heart, aorta and brain, and (2) with a pI = 7.9 and 7.1, specific for liver and kidney [19].
  • The subsequent sequence analysis of this abnormal fragment revealed homozygous and heterozygous A-->G substitutions in the proband and in the parents and brother respectively at codon 164, corresponding to a tyrosine-->cysteine substitution in the AK protein [31].
  • On reperfusion, AK1 knockout hearts demonstrated reduced nucleotide salvage, resulting in lower ATP, GTP, ADP, and GDP levels and an altered metabolic steady state associated with diminished ATP-to-P(i) and creatine phosphate-to-P(i) ratios [32].
  • We also used Southern blot analysis and a radiation hybrid cell line, E6B, to exclude 3 genes--PBX3A, RXR alpha, and TAN1--from the AK1 to D9S114 interval [33].


  1. Red cell adenylate kinase deficiency associated with hereditary nonspherocytic hemolytic anemia: clinical and biochemical studies. Miwa, S., Fujii, H., Tani, K., Takahashi, K., Takizawa, T., Igarashi, T. Am. J. Hematol. (1983) [Pubmed]
  2. Gene structures of three vertebrate adenylate kinase isozymes. Nakazawa, A., Yamada, M., Tanaka, H., Shahjahan, M., Tanabe, T. Prog. Clin. Biol. Res. (1990) [Pubmed]
  3. Regional assignment of the loci for adenylate kinase to 9q32 and for alpha 1-acid glycoprotein to 9q31-q32. A locus for Goltz syndrome in region 9q32-qter? Zuffardi, O., Caiulo, A., Maraschio, P., Tupler, R., Bianchi, E., Amisano, P., Beluffi, G., Moratti, R., Liguri, G. Hum. Genet. (1989) [Pubmed]
  4. Evidence for the assignment of the loci AK1, AK3 and ACONs to chromosome 9 in man. Povey, S., Slaughter, C.A., Wilson, D.E., Gormley, I.P., Buckton, K.E., Perry, P., Bobrow, M. Ann. Hum. Genet. (1976) [Pubmed]
  5. No association of red cell adenylate kinase phenotypes with affective disorders. Beckman, G., Beckman, L., Perris, C., Strandman, E. Hum. Genet. (1978) [Pubmed]
  6. A case of complete adenylate kinase deficiency due to a nonsense mutation in AK-1 gene (Arg 107 --> Stop, CGA --> TGA) associated with chronic haemolytic anaemia. Bianchi, P., Zappa, M., Bredi, E., Vercellati, C., Pelissero, G., Barraco, F., Zanella, A. Br. J. Haematol. (1999) [Pubmed]
  7. Signs of brain cell injury during open heart operations: past and present. Aberg, T. Ann. Thorac. Surg. (1995) [Pubmed]
  8. Dementia--and adenylate kinase activity in cerebrospinal fluid. Ahlberg, J., Blomstrand, C., Ronquist, G., Wikkelsö, C. Acta neurologica Scandinavica. (1985) [Pubmed]
  9. The structure and regulation of protein phosphatases. Cohen, P. Annu. Rev. Biochem. (1989) [Pubmed]
  10. An intrinsic adenylate kinase activity regulates gating of the ABC transporter CFTR. Randak, C., Welsh, M.J. Cell (2003) [Pubmed]
  11. Injection of the cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation. Dash, P.K., Hochner, B., Kandel, E.R. Nature (1990) [Pubmed]
  12. Identification of hypoxically inducible mRNAs in HeLa cells using differential-display PCR. Role of hypoxia-inducible factor-1. O'Rourke, J.F., Pugh, C.W., Bartlett, S.M., Ratcliffe, P.J. Eur. J. Biochem. (1996) [Pubmed]
  13. Hereditary disorders of erythrocyte enzymes in non-glycolytic metabolic pathways. Paglia, D.E., Valentine, W.N. Haematologia (Budap) (1982) [Pubmed]
  14. Effects of ciprofloxacin, norfloxacin, and ofloxacin on in vitro adhesion and survival of Pseudomonas aeruginosa AK1 on urinary catheters. Reid, G., Sharma, S., Advikolanu, K., Tieszer, C., Martin, R.A., Bruce, A.W. Antimicrob. Agents Chemother. (1994) [Pubmed]
  15. Distribution of adenylate kinase and phosphoglucomutase isoenzymes in the population of the city of New York. Mondovano, J.A., Gaensslen, R.E. Hum. Hered. (1975) [Pubmed]
  16. Phosphoglucomutase, adenylate kinase and acid phosphatase polymorphism in some Jewish populations of Israel. Kobyliansky, E., Micl'e, S., Goldschmidt-Nathan, M., Arensburg, B., Nathan, H. Acta anthropogenetica. (1980) [Pubmed]
  17. Identification of a novel adenylate kinase system in the brain: cloning of the fourth adenylate kinase. Yoneda, T., Sato, M., Maeda, M., Takagi, H. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  18. Cloning and expression of human adenylate kinase 2 isozymes: differential expression of adenylate kinase 1 and 2 in human muscle tissues. Lee, Y., Kim, J.W., Lee, S.M., Kim, H.J., Lee, K.S., Park, C., Choe, I.S. J. Biochem. (1998) [Pubmed]
  19. Multiforms of mammalian adenylate kinase and its monoclonal antibody against AK1. Kurokawa, Y., Takenaka, H., Sumida, M., Oka, K., Hamada, M., Kuby, S.A. Enzyme (1990) [Pubmed]
  20. Dynamics of nucleotide metabolism as a supporter of life phenomena. Noma, T. J. Med. Invest. (2005) [Pubmed]
  21. Adenylate kinase 2, a mitochondrial enzyme. Bruns, G.A., Regina, V.M. Biochem. Genet. (1977) [Pubmed]
  22. A novel nuclear-localized protein with special adenylate kinase properties from Caenorhabditis elegans. Zhai, R., Meng, G., Zhao, Y., Liu, B., Zhang, G., Zheng, X. FEBS Lett. (2006) [Pubmed]
  23. Metabolic compensation for profound erythrocyte adenylate kinase deficiency. A hereditary enzyme defect without hemolytic anemia. Beutler, E., Carson, D., Dannawi, H., Forman, L., Kuhl, W., West, C., Westwood, B. J. Clin. Invest. (1983) [Pubmed]
  24. Inhibition of ATPase, GTPase and adenylate kinase activities of the second nucleotide-binding fold of the cystic fibrosis transmembrane conductance regulator by genistein. Randak, C., Auerswald, E.A., Assfalg-Machleidt, I., Reenstra, W.W., Machleidt, W. Biochem. J. (1999) [Pubmed]
  25. Study on ATP-generating system and related hexokinase activity in mitochondria isolated from undifferentiated or differentiated HT29 adenocarcinoma cells. Gauthier, T., Denis-Pouxviel, C., Paris, H., Murat, J.C. Biochim. Biophys. Acta (1989) [Pubmed]
  26. Expression of the human adenylate kinase isozymes, phosphopyruvate hydratase, 6-phosphogluconate dehydrogenase, and phosphoglucomutase-1 in man-rodent somatic cell hybrids. Bruns, G.A., Gerald, P.S. Biochem. Genet. (1976) [Pubmed]
  27. The purine nucleotide cycle as two temporally separated metabolic units: a study on trout muscle. Mommsen, T.P., Hochachka, P.W. Metab. Clin. Exp. (1988) [Pubmed]
  28. Polymorphism of red cell phosphoglucomutase, adenylate kinase and adenosine deaminase in a Polish population. Turowska, B. Hum. Hered. (1975) [Pubmed]
  29. Population data of five genetic markers in the Turkish population: comparison with four American population groups. Kurtuluş-Ulküer, M., Ulküer, U., Kesici, T., Menevşe, S. Anthropologischer Anzeiger; Bericht über die biologisch-anthropologische Literatur. (2002) [Pubmed]
  30. Genetic polymorphisms of the Caucasus ethnic groups: distribution of some serum protein and red cell enzyme genetic markers (Part I). Nasidze, I.S. Gene geography : a computerized bulletin on human gene frequencies. (1995) [Pubmed]
  31. Severe erythrocyte adenylate kinase deficiency due to homozygous A-->G substitution at codon 164 of human AK1 gene associated with chronic haemolytic anaemia. Qualtieri, A., Pedace, V., Bisconte, M.G., Bria, M., Gulino, B., Andreoli, V., Brancati, C. Br. J. Haematol. (1997) [Pubmed]
  32. Adenylate kinase AK1 knockout heart: energetics and functional performance under ischemia-reperfusion. Pucar, D., Bast, P., Gumina, R.J., Lim, L., Drahl, C., Juranic, N., Macura, S., Janssen, E., Wieringa, B., Terzic, A., Dzeja, P.P. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  33. A 5.4-Mb continuous pulsed-field gel electrophoresis map of human 9q34.1 between ABL and D9S114, including the tuberous sclerosis (TSC1) region. Henske, E.P., Kwiatkowski, D.J. Genomics (1995) [Pubmed]
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