5'-AMP-activated protein kinase beta subunit, interation domain
SMART accession number:
SM01010
Description:
This region is found in the beta subunit of the 5'-AMP-activated protein kinase complex, and its yeast homologues Sip1, Sip2 and Gal83, which are found in the SNF1 kinase complex. This region is sufficient for interaction of this subunit with the kinase complex, but is not solely responsible for the interaction, and the interaction partner is not known. The isoamylase N-terminal domain is sometimes found in proteins belonging to this family.
Association with the SNF1 complex (ASC) domain is found in the Sip1/Sip2/Gal83/AMPKbeta subunits of the SNF1/AMP-activated protein kinase (AMPK) complex [ (PUBMED:11252725) ]. SNF1/AMPK are heterotrimeric enzymes composed of a catalytic alpha-subunit, a regulatory gamma-subunit and a regulatory/targeting beta-subunit [ (PUBMED:9121458) ]. Saccharomyces cerevisiae encodes three beta-subunit genes, Sip1, Sip2 and Gal83 [ (PUBMED:7813428) (PUBMED:10990457) ]. The beta-subunits function as target selective adaptors that recruit the catalytic kinase and regulator Snf4/gamma-subunits. The ASC domain is required for interaction with Snf4 [ (PUBMED:11252725) (PUBMED:9121458) ].
The SNF1 kinase complex is required for transcriptional, metabolic, and developmental adaptations in response to glucose limitation [ (PUBMED:17981722) (PUBMED:10207618) ]. As glucose levels decrease, Snf1 is activated and promotes the use of alternative carbon sources.
Non-catalytic beta- and gamma-subunit isoforms of the 5'-AMP-activatedprotein kinase.
J Biol Chem. 1996; 271: 8675-81
Display abstract
The mammalian 5'-AMP-activated protein kinase (AMPK) is a heterotrimericprotein consisting of alpha-, beta-, and gamma-subunits. The alpha-subunitis the catalytic subunit and is related to the yeast Snf1p kinase. In thisstudy, we report the cloning of full-length cDNAs for the non-catalyticbeta- and gamma-subunits. The rat liver AMPK beta-subunit clone predicts aprotein of 30,464 Da, which is related to the Sip1p, Sip2p, and Gal83psubfamily of yeast proteins that interact with Snf1p and are involved inglucose regulation of gene expression. The AMPK beta-subunit, whenexpressed in bacteria and in mammalian cells, migrates anomalously on SDSgels at an apparent molecular mass of 40 kDa. Rat and human liver AMPKgamma-subunit clones predict a protein of 37,577 Da (AMPK-gamma1), whichis related to the yeast Snf4p protein that copurifies with Snf1p and to alarger family of other human AMPK gamma-isoforms. The mRNAs for both AMPK-beta and AMPK-gamma1 are widely expressed in rat tissues, consistent witha broad role for AMPK in cellular regulation. These data reveal amammalian multisubunit protein kinase strikingly similar to themultisubunit glucose-sensing Snf1 kinase complex. The identification ofisoform families for the AMPK subunits indicates the potential diversityof the roles of this highly conserved signaling system in nutrientregulation and utilization in mammalian cells.
A family of proteins containing a conserved domain that mediatesinteraction with the yeast SNF1 protein kinase complex.
EMBO J. 1994; 13: 5878-86
Display abstract
The SNF1 protein kinase is required for the regulatory response to glucosestarvation in Saccharomyces cerevisiae. SNF1 is a protein serine/threoninekinase that has been widely conserved in both plants and mammals.Previously, we identified SIP1 and SIP2 as proteins that interact withSNF1 in vivo by the two-hybrid system. We have cloned the SIP2 gene andthe encoded protein is homologous to SIP1 and to GAL83, which affectsglucose repression of the GAL genes. We show that SIP2 and GAL83, likeSIP1, co-immunoprecipitate with SNF1 and are phosphorylated in vitro. An80 amino acid sequence, designated the ASC domain, is highly conserved atthe C-termini of all three proteins. We show that this small domain canmediate protein-protein interaction with the SNF1 kinase complex. Thus,SIP1, SIP2 and GAL83 define a family of homologous proteins that aretightly associated with the SNF1 kinase, probably in alternative forms ofthe complex. Genetic evidence suggests that the three proteins havedistinct, but related, functions in the SNF1 pathway, and deletion ofGAL83 dramatically reduces SNF1 activity in immune complex assays. Wepropose that SIP1, SIP2 and GAL83 act as adaptors that promote theactivity of SNF1 towards specific targets.
Crystal structure of the adenylate sensor from AMP-activated protein kinase in complex with 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranotide (ZMP)
