Disease relevance of ADK1

• Frameshift mutations obtained after in vitro and in vivo mutagenesis were capable of complementing the adk1 temperature-conditional deficiency in Escherichia coli, indicating that the frameshift led to the expression of a protein that could phosphorylate AMP [1].

High impact information on ADK1

• A Ura6 mutant protein in which helix 5 had been replaced with the respective sequence from Aky2p was imported, and this address sequence cooperates with the N terminus in the respective double mutant in a synergistic fashion [2].
• Yeast adenylate kinase (Aky2p, Adk1p) occurs simultaneously in cytoplasm and mitochondrial intermembrane space [2].
• The extreme N terminus of Aky2p is able to direct cytoplasmic passengers to mitochondria [2].
• Thus, nascent Adk1p/Aky2p has two options: either it is synthesized to completion and folds into an enzymatically active import-incompetent conformation that remains in the cytosol; or, during synthesis and before commencement of significant tertiary structure formation, it reaches a mitochondrial surface receptor and is internalized [3].
• This is in contrast to the ADK1 gene of S. cerevisiae, the deletion of which was shown to lead to a slower cell growth rate rather than to a lethal phenotype [4].

Biological context of ADK1

• By gene disruption it is shown that the ADK1 gene is needed for normal cell proliferation but is not essential for cell viability [5].
• The gene (designated ADK1) encoding the so-called cytosolic adenylate kinase of the yeast Saccharomyces cerevisiae was isolated using a single mixed oligonucleotide hybridization probe designed from the published amino acid sequence [5].
• A cDNA clone encoding immunoreactive adenylate kinase from S. pombe was isolated from a lambda gt11 expression library by cross-reaction with antibodies raised against the recently characterized ADK1 enzyme from the budding yeast Saccharomyces cerevisiae [4].
• C. boidinii cells were transformed with plasmids harboring the S. cerevisiae ADK1 gene under the alcohol oxidase (C. boidinii AOD1) promoter [6].
• As the expression of the S. cerevisiae ADK1 in C. boidinii was under similar regulation to that of the C. boidinii AOD1, the previously cloned 1.7-kb AOD1 promoter fragment was proved to harbor sufficient cis elements for AOD1 regulation and found to be an efficient promoter for heterologous gene expression [6].

Associations of ADK1 with chemical compounds

• ADK1 was found to be identical to an adenylate kinase gene recently isolated by an approach entirely different from ours (Magdolen, V., Oechsner, U., and Bandlow, W. (1987) Curr. Genet. 12, 405-411) [5].
• Methanol-induced transformants had 10,000-fold enhanced levels of ADK activity and produced 23-fold more ATP from adenosine when compared to the control, parent strain [7].

Analytical, diagnostic and therapeutic context of ADK1

• Site-directed mutagenesis and deletions were used to study mitochondrial import of a major yeast adenylate kinase, Aky2p [8].
• In the wild type two AKY2-derived signals (a major and a minor one) were detected by a monospecific antibody after two-dimensional gel electrophoresis and Western blotting [9].

References