Human Gene PRKAG3 (uc002vjb.1) Description and Page Index
  Description: Homo sapiens protein kinase, AMP-activated, gamma 3 non-catalytic subunit (PRKAG3), mRNA.
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]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: AJ249977.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA2158800, SAMEA2162946 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## NMD candidate :: translation inferred from conservation RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr2:219,687,106-219,696,512 Size: 9,407 Total Exon Count: 14 Strand: -
Coding Region
   Position: hg19 chr2:219,688,485-219,696,493 Size: 8,009 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:219,687,106-219,696,512)mRNA (may differ from genome)Protein (489 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  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.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PRKAG3
CDC HuGE Published Literature: PRKAG3
Positive Disease Associations: Macular Degeneration
Related Studies:
  1. Macular Degeneration
    , , . [PubMed 0]

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 12.78 RPKM in Muscle - Skeletal
Total median expression: 14.86 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -5.7019-0.300 Picture PostScript Text
3' UTR -267.48810-0.330 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000644 - Cysta_beta_synth_core

Pfam Domains:
PF00571 - CBS domain

SCOP Domains:
54631 - CBS-domain

ModBase Predicted Comparative 3D Structure on Q9UGI9
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004679 AMP-activated protein kinase activity
GO:0005524 ATP binding
GO:0019901 protein kinase binding

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

Cellular Component:
GO:0005615 extracellular space
GO:0005654 nucleoplasm
GO:0005829 cytosol
GO:0031588 nucleotide-activated protein kinase complex


-  Descriptions from all associated GenBank mRNAs
  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.
JD131145 - Sequence 112169 from Patent EP1572962.
JD321412 - Sequence 302436 from Patent EP1572962.
JD108866 - Sequence 89890 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
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04910 - Insulin signaling pathway
hsa04920 - Adipocytokine signaling pathway
hsa05410 - Hypertrophic cardiomyopathy (HCM)

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):

R-HSA-380930 Phosphorylated AMPK binds AMP
R-HSA-380949 AMPK is dephosphorylated
R-HSA-200421 Activation of cytosolic AMPK by phosphorylation
R-HSA-5631941 SESN1,2,3 bind AMPK
R-HSA-5672011 p-AMPK:AMP binds the ULK complex
R-HSA-6805470 AMPK phosphorylates TP53
R-HSA-5665868 AMPK (complex) phosphorylates ULK1 (complex)
R-HSA-5675868 ULK1 phosphorylates ATG13 and RB1CC1
R-HSA-5679239 ULK complex translocates to the ER
R-HSA-380927 p-AMPK phosphorylates TSC1:TSC2
R-HSA-447074 AMPK phosphorylates Raptor in the mTORC1 complex
R-HSA-5673768 p-AMPK:AMP phosphorylates Raptor in the mTORC1 complex
R-HSA-1454699 AMPK-alpha2 phosphorylates TBC1D1
R-HSA-1592244 AMPK phosphorylates PPARGC1A
R-HSA-1632857 ULK1 phosphorylates AMBRA1:Beclin-1 complex
R-HSA-5679205 ULK1 phosphorylates Beclin-1
R-HSA-380972 Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-5628897 TP53 Regulates Metabolic Genes
R-HSA-1632852 Macroautophagy
R-HSA-165159 mTOR signalling
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
R-HSA-3700989 Transcriptional Regulation by TP53
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-162582 Signal Transduction
R-HSA-1445148 Translocation of GLUT4 to the plasma membrane
R-HSA-2151209 Activation of PPARGC1A (PGC-1alpha) by phosphorylation
R-HSA-5633007 Regulation of TP53 Activity
R-HSA-212436 Generic Transcription Pathway
R-HSA-199991 Membrane Trafficking
R-HSA-1592230 Mitochondrial biogenesis
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-5653656 Vesicle-mediated transport
R-HSA-1852241 Organelle biogenesis and maintenance
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: AAKG3_HUMAN, AMPKG3, NM_017431, NP_059127, Q4QQG8, Q4V779, Q9NRL1, Q9UGI9
UCSC ID: uc002vjb.1
RefSeq Accession: NM_017431
Protein: Q9UGI9 (aka AAKG3_HUMAN or AAKI_HUMAN)
CCDS: CCDS2424.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: yes RNA accession: NM_017431.2
exon count: 14CDS single in 3' UTR: no RNA size: 2299
ORF size: 1470CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2740.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.