5'-AMP-activated protein kinase subunit gamma-1 (PRKAG1)
The protein contains 331 amino acids for an estimated molecular weight of 37579 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs1126930 | |
| dbSNP:rs34210356 |
Biological Process
Cell cycle arrest
Cellular response to glucose starvation
Fatty acid biosynthetic process
Import into nucleus
Insulin receptor signaling pathway
Macroautophagy
Membrane organization
Mitochondrion organization
Organelle organization
Positive regulation of gene expression
Positive regulation of protein kinase activity
Protein heterooligomerization
Protein phosphorylation
Regulation of catalytic activity
Regulation of glycolytic process
Regulation of macroautophagy
Regulation of protein serine/threonine kinase activity
Regulation of signal transduction by p53 class mediator
Signal transduction
Spermatogenesis
The reference OMIM entry for this protein is 602742
Protein kinase, amp-activated, noncatalytic, gamma-1; prkag1
Amp-activated protein kinase, noncatalytic, gamma-1
Ampk-gamma-1
DESCRIPTION
AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that is activated by various cellular stresses that increase AMP levels and decrease ATP levels. Once activated, AMPK switches on catabolic pathways and switches off many ATP-consuming processes. AMPK is a heterotrimeric complex consisting of a catalytic alpha subunit (e.g., PRKAA1; 602739), a noncatalytic beta subunit (e.g., PRKAB1; 6027740), and a noncatalytic gamma subunit (e.g., PRKAG1). AMPK is evolutionarily conserved, and orthologs for all 3 subunits are found throughout eukaryotes (review by Sanz, 2008).CLONING
By PCR with degenerate oligonucleotides based on the rat Ampk-gamma-1 protein sequence, Woods et al. (1996) isolated rat liver cDNAs encoding Ampk-gamma-1. Both the Ampk-gamma-1 mRNA and protein are widely expressed in rat tissues. Gao et al. (1996) screened a human fetal liver cDNA library with the rat Ampk-gamma-1 cDNA and isolated a cDNA encoding AMPK-gamma-1. The predicted 331-amino acid human protein has a mass of 37.5 kD by SDS-PAGE.GENE FUNCTION
By site-directed mutagenesis, Hamilton et al. (2001) introduced an arg70-to-glu mutation into PRKAG1. The mutation caused a marked increase in AMPK activity, and the activity was largely AMP-independent. Activation was associated with increased threonine phosphorylation within the activation loop of the alpha subunit, PRKAA1. There was also increased phosphorylation of one of its major substrates, acetyl-CoA carboxylase (200350). Minokoshi et al. (2004) investigated the potential role of AMP-activated protein kinase (AMPK) in the hypothalamus in the regulation of food intake. Minokoshi et al. (2004) reported that AMPK activity is inhibited in arcuate and paraventricular hypothalamus by the anorexigenic hormone leptin (164160), and in multiple hypothalamic regions by insulin (176730), high glucose, and refeeding. A melanocortin receptor (see 155555) agonist, a potent anorexigen, decreased AMPK activity in paraventricular hypothalamus, whereas agouti-related protein (602311), an orexigen, increased AMPK activity. Melanocortin receptor signaling is required for leptin and refeeding effects of AMPK in the paraventricular hypothalamus. Dominant-negative AMPK expression in the hypothalamus was sufficient to reduce food intake and body weight, whereas constitutively active AMPK increased both. Alterations of hypothalamic AMPK activity augmented changes in arcuate neuropeptide expression induced by fasting and feeding. Furthermore, inhibition of hypothalamic AMPK is necessary for leptin's effects on food intake and body weight, as constitutively active AMPK blocks these effects. Thus, Minokoshi et al. (2004) concluded that hypothalamic AMPK plays a critical role in hormonal and nutrient-derived anorexigenic and orexigenic signals and in energy balance. Baba et al. (2006) showed that FNIP1 (610594) interacted with the alpha, beta, and gamma subunits of AMPK. FNIP1 was phosphorylated by AMPK, and its phosphorylation was inhibited in a dose-dependent manner by an AMPK inhibitor, resulting in reduced FNIP1 expression. FLCN (607273) phosphorylation was diminished by rapamycin and amino acid starvation and facilitated by FNIP1 overexpression, suggesting that FLCN phosphorylation may be regulated by mTOR (FRAP1; 601231) and AMPK signaling. Baba et al. (2006) concluded that FLCN and FNIP1 may be involved in energy and/or nutrient sensing through the AMPK and mTOR signalin ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 16, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 26, 2017: Protein entry updated
Automatic update: model status changed
March 15, 2016: Protein entry updated
Automatic update: OMIM entry 602742 was added.
Sept. 16, 2015: Protein entry updated
Automatic update: model status changed