Human Gene PRKAG3 (ENST00000439262.7) from GENCODE V44
Description: Homo sapiens protein kinase AMP-activated non-catalytic subunit gamma 3 (PRKAG3), mRNA. (from RefSeq NM_017431) RefSeq Summary (NM_017431): The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit is one of the gamma regulatory subunits of AMPK. It is dominantly expressed in skeletal muscle. Studies of the pig counterpart suggest that this subunit may play a key role in the regulation of energy metabolism in skeletal muscle. [provided by RefSeq, Jul 2008]. Gencode Transcript: ENST00000439262.7 Gencode Gene: ENSG00000115592.13 Transcript (Including UTRs) Position: hg38 chr2:218,822,308-218,831,803 Size: 9,496 Total Exon Count: 14 Strand: - Coding Region Position: hg38 chr2:218,823,762-218,831,770 Size: 8,009 Coding Exon Count: 13
ID:AAKG3_HUMAN DESCRIPTION: RecName: Full=5'-AMP-activated protein kinase subunit gamma-3; Short=AMPK gamma3; Short=AMPK subunit gamma-3; FUNCTION: AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive. SUBUNIT: AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non- catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2 (By similarity). TISSUE SPECIFICITY: Skeletal muscle, with weak expression in heart and pancreas. DOMAIN: The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1. DOMAIN: The CBS domains mediate binding to AMP, ADP and ATP. 2 sites bind either AMP or ATP, whereas a third site contains a tightly bound AMP that does not exchange. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. PTM: Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK. SIMILARITY: Belongs to the 5'-AMP-activated protein kinase gamma subunit family. SIMILARITY: Contains 4 CBS domains.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UGI9
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0005978 glycogen biosynthetic process GO:0006096 glycolytic process GO:0006468 protein phosphorylation GO:0006629 lipid metabolic process GO:0006631 fatty acid metabolic process GO:0006633 fatty acid biosynthetic process GO:0007050 cell cycle arrest GO:0014873 response to muscle activity involved in regulation of muscle adaptation GO:0016236 macroautophagy GO:0035556 intracellular signal transduction
AJ249977 - Homo sapiens mRNA for AMP-activated protein kinase gamma 3 subunit (AMPK gamma 3 gene). AF214519 - Homo sapiens AMP-activated protein kinase gamma subunit (PRKAG3) mRNA, complete cds. JD092853 - Sequence 73877 from Patent EP1572962. JD165882 - Sequence 146906 from Patent EP1572962. JD149965 - Sequence 130989 from Patent EP1572962. JD114153 - Sequence 95177 from Patent EP1572962. JD143306 - Sequence 124330 from Patent EP1572962. JD231611 - Sequence 212635 from Patent EP1572962. AK300078 - Homo sapiens cDNA FLJ51967 complete cds, highly similar to 5'-AMP-activated protein kinase subunit gamma-3. JD073118 - Sequence 54142 from Patent EP1572962. JD040096 - Sequence 21120 from Patent EP1572962. JD556554 - Sequence 537578 from Patent EP1572962. JD122940 - Sequence 103964 from Patent EP1572962. BC098102 - Homo sapiens protein kinase, AMP-activated, gamma 3 non-catalytic subunit, mRNA (cDNA clone MGC:119342 IMAGE:40005880), complete cds. BC098255 - Homo sapiens protein kinase, AMP-activated, gamma 3 non-catalytic subunit, mRNA (cDNA clone MGC:119343 IMAGE:40005883), complete cds. BC098277 - Homo sapiens protein kinase, AMP-activated, gamma 3 non-catalytic subunit, mRNA (cDNA clone MGC:119344 IMAGE:40005886), complete cds. BC098306 - Homo sapiens protein kinase, AMP-activated, gamma 3 non-catalytic subunit, mRNA (cDNA clone MGC:119345 IMAGE:40005888), complete cds. JD155616 - Sequence 136640 from Patent EP1572962. JD519469 - Sequence 500493 from Patent EP1572962. KJ893997 - Synthetic construct Homo sapiens clone ccsbBroadEn_03391 PRKAG3 gene, encodes complete protein. KR711482 - Synthetic construct Homo sapiens clone CCSBHm_00024344 PRKAG3 (PRKAG3) mRNA, encodes complete protein. AK300687 - Homo sapiens cDNA FLJ60036 complete cds, highly similar to 5'-AMP-activated protein kinase subunit gamma-3. AK309865 - Homo sapiens cDNA, FLJ99906.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_leptinPathway - Reversal of Insulin Resistance by Leptin h_chrebpPathway - ChREBP regulation by carbohydrates and cAMP
Reactome (by CSHL, EBI, and GO)
Protein Q9UGI9 (Reactome details) participates in the following event(s):
US Server
