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Description

AMP-activated protein kinase alpha subunit, isoform A (EC 2.7.11.16, UniProt O18645, also known as AMP-activated protein kinase alpha subunit, isoform B, AMP-activated protein kinase alpha subunit, isoform C, EG:132E8.2 protein, FI03728p, SNF1A/AMP-activated protein kinase) is encoded by the AMPKalpha (also known as EG:132E8.2, SNF1A, SNF1A-RA) gene (ORF CG3051/Dmel_CG3051, Gene ID 43904) in Drosophila melanogaster (Fruit fly) species. The yeast sucrose non-fermenting 1 (SNF1) and the AMP-activated protein kinase (AMPK) in drosphila and mammals are orthologous heterotrimeric serine-threonine kinases, each consisting of a catalytic &alpha, subunit and regulatory &beta, and &gamma, subunits, that sense decreased cellular energy levels when the AMP to ATP ratio rises due to a high rate of metabolism or decreased nutrient availability. AMP binding to the &gamma, subunit results in an enhanced phosphorylation of the catalytic &alpha, subunit on an activation loop threonine and AMPK allosteric activation. Activated AMPK phosphorylates downstream targets, leading to energy conservation and inhibition of ATP consumption. For example, the high rate of ATP use in contracting muscle causes AMPK-mediated phosphorylation/inactivation of acetyl-CoA carboxylase (ACC), thereby increasing fatty acid oxidation and restoring cellular energy. AMPK functions as a positive regulator of autophagy by phosphorylating the protein kinase ULK1 that initiates autophagy as well as by inhibiting the mammalian TOR (mTOR) pathway activity via phosphorylating mTOR-binding partner raptor. In mammals, there exist two different &alpha, (encoded by the PRKAA1 and PRKAA2 gene), two different &beta, (encoded by the PRKAB1 and PRKAB2 gene), and three different &gamma, (encoded by the PRKAG1, PRKAG2, and PRKAG3 gene) subunits.