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Aliases for PRKAG3 Gene

Aliases for PRKAG3 Gene

  • Protein Kinase AMP-Activated Non-Catalytic Subunit Gamma 3 2 3 5
  • Protein Kinase, AMP-Activated, Gamma 3 Non-Catalytic Subunit 2 3
  • AMPK Subunit Gamma-3 3 4
  • AMPK Gamma3 3 4
  • AMPKG3 3 4
  • 5-AMP-Activated Protein Kinase, Gamma-3 Subunit 3
  • 5-AMP-Activated Protein Kinase Subunit Gamma-3 3
  • AMPK Gamma-3 Chain 3

External Ids for PRKAG3 Gene

Previous GeneCards Identifiers for PRKAG3 Gene

  • GC02M217702
  • GC02M218408
  • GC02M219651
  • GC02M219889
  • GC02M219512
  • GC02M219395
  • GC02M211540

Summaries for PRKAG3 Gene

Entrez Gene Summary for PRKAG3 Gene

  • 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]

GeneCards Summary for PRKAG3 Gene

PRKAG3 (Protein Kinase AMP-Activated Non-Catalytic Subunit Gamma 3) is a Protein Coding gene. Among its related pathways are Longevity regulating pathway and Nanog in Mammalian ESC Pluripotency. GO annotations related to this gene include protein kinase binding and adenyl nucleotide binding. An important paralog of this gene is PRKAG2.

UniProtKB/Swiss-Prot for PRKAG3 Gene

  • 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.

Gene Wiki entry for PRKAG3 Gene

Additional gene information for PRKAG3 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PRKAG3 Gene

Genomics for PRKAG3 Gene

Regulatory Elements for PRKAG3 Gene

Enhancers for PRKAG3 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH02H218908 2 FANTOM5 Ensembl ENCODE dbSUPER 10.7 -77.5 -77513 2.4 HDGF PKNOX1 FOXA2 MLX ARNT ZFP64 ARID4B SIN3A DMAP1 ZBTB7B CNOT9 STK36 ZNF142 USP37 AAMP OBSL1 NHEJ1 CDK5R2 ENSG00000235024 ENSG00000269068
GH02H218781 1.6 FANTOM5 Ensembl ENCODE 11.6 +48.5 48473 6 PKNOX1 FOXA2 MLX ZFP64 ARID4B DMAP1 YY1 FOS SP5 MXD4 CYP27A1 PLCD4 TTLL4 PRKAG3 PNKD SLC11A1 RNF25 TMBIM1 ENSG00000272555
GH02H218743 1.5 Ensembl ENCODE dbSUPER 10.9 +87.0 87003 3.6 HDGF PKNOX1 ATF1 ARNT ARID4B DMAP1 ATF7 RUNX3 NCOA1 JUNB CYP27A1 PLCD4 TTLL4 PRKAG3 STK36 RNF25 GC02P218766
GH02H218886 1.4 FANTOM5 ENCODE dbSUPER 10.8 -54.3 -54314 0.5 HDGF TBL1XR1 MAX EBF1 RELA POLR2A EED ZNF143 ATF7 RCOR1 WNT6 RNU6-642P PRKAG3 LINC00608 FEV CRYBA2 WNT10A CNOT9 LOC105373882
GH02H218876 1.1 ENCODE dbSUPER 10.4 -44.7 -44728 0.2 CTCF FOXA2 SUZ12 IRF3 ZNF384 RAD21 RELA ZNF316 SMC3 ZNF143 PRKAG3 LOC100129175 MIR375 WNT10A LOC105373882
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around PRKAG3 on UCSC Golden Path with GeneCards custom track

Genomic Locations for PRKAG3 Gene

Genomic Locations for PRKAG3 Gene
chr2:218,822,383-218,832,086
(GRCh38/hg38)
Size:
9,704 bases
Orientation:
Minus strand
chr2:219,687,106-219,696,809
(GRCh37/hg19)

Genomic View for PRKAG3 Gene

Genes around PRKAG3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PRKAG3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PRKAG3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PRKAG3 Gene

Proteins for PRKAG3 Gene

  • Protein details for PRKAG3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UGI9-AAKG3_HUMAN
    Recommended name:
    5-AMP-activated protein kinase subunit gamma-3
    Protein Accession:
    Q9UGI9
    Secondary Accessions:
    • Q4QQG8
    • Q4V779
    • Q9NRL1

    Protein attributes for PRKAG3 Gene

    Size:
    489 amino acids
    Molecular mass:
    54258 Da
    Quaternary structure:
    • 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).

    Alternative splice isoforms for PRKAG3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PRKAG3 Gene

Post-translational modifications for PRKAG3 Gene

  • Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PRKAG3 Gene

No data available for DME Specific Peptides for PRKAG3 Gene

Domains & Families for PRKAG3 Gene

Protein Domains for PRKAG3 Gene

InterPro:
Blocks:
ProtoNet:

Graphical View of Domain Structure for InterPro Entry

Q9UGI9

UniProtKB/Swiss-Prot:

AAKG3_HUMAN :
  • 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.
  • Belongs to the 5-AMP-activated protein kinase gamma subunit family.
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.
  • The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2- and 3-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.
Family:
  • Belongs to the 5-AMP-activated protein kinase gamma subunit family.
genes like me logo Genes that share domains with PRKAG3: view

Function for PRKAG3 Gene

Molecular function for PRKAG3 Gene

UniProtKB/Swiss-Prot 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.

Phenotypes From GWAS Catalog for PRKAG3 Gene

Gene Ontology (GO) - Molecular Function for PRKAG3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004679 AMP-activated protein kinase activity TAS,IEA --
GO:0005524 ATP binding IEA --
GO:0016301 kinase activity IEA --
GO:0019901 protein kinase binding IDA 10698692
genes like me logo Genes that share ontologies with PRKAG3: view
genes like me logo Genes that share phenotypes with PRKAG3: view

Animal Models for PRKAG3 Gene

MGI Knock Outs for PRKAG3:

Animal Model Products

miRNA for PRKAG3 Gene

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PRKAG3 Gene

Localization for PRKAG3 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PRKAG3 gene
Compartment Confidence
extracellular 5
cytosol 5
nucleus 4
plasma membrane 3
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for PRKAG3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IDA 22664934
GO:0005654 nucleoplasm TAS --
GO:0005829 cytosol TAS --
GO:0031588 nucleotide-activated protein kinase complex IEA --
genes like me logo Genes that share ontologies with PRKAG3: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot and Subcellular locations from the Human Protein Atlas (HPA) for PRKAG3 Gene

Pathways & Interactions for PRKAG3 Gene

genes like me logo Genes that share pathways with PRKAG3: view

SIGNOR curated interactions for PRKAG3 Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for PRKAG3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005978 glycogen biosynthetic process IEA --
GO:0006468 protein phosphorylation IEA --
GO:0006629 lipid metabolic process IEA --
GO:0006631 fatty acid metabolic process IEA --
GO:0006633 fatty acid biosynthetic process IEA --
genes like me logo Genes that share ontologies with PRKAG3: view

Drugs & Compounds for PRKAG3 Gene

(15) Drugs for PRKAG3 Gene - From: DrugBank and ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Aspirin Approved, Vet_approved Pharma Channel blocker, Target, activator 1196
AICAR Experimental Pharma AMPK activator 0
Imeglimin Investigational Pharma Antidiabetic agent 0
AICAR phosphate Pharma AMPK activator 0
Dorsomorphin Pharma AMPK inhibitor 0

(14) ApexBio Compounds for PRKAG3 Gene

Compound Action Cas Number
AICAR AMPK activator 2627-69-2
AICAR phosphate AMPK activator 681006-28-0
Dorsomorphin AMPK inhibitor 866405-64-3
Dorsomorphin 2HCl AMPK inhibitor 1219168-18-9
GSK621 AMPK agonist 1346607-05-3
Imeglimin Antidiabetic agent 775351-65-0
Imeglimin hydrochloride Antidiabetic agent 775351-61-6
Phenformin HCl 834-28-6
PT 1 AMPK activator, selective 331002-70-1
RSVA 405 140405-36-3
SAMS Peptide 125911-68-4
YLF-466D 1273323-67-3
ZLN024 723249-01-2
ZLN024 hydrochloride
genes like me logo Genes that share compounds with PRKAG3: view

Drug Products

Transcripts for PRKAG3 Gene

mRNA/cDNA for PRKAG3 Gene

(2) REFSEQ mRNAs :
(8) Additional mRNA sequences :
(10) Selected AceView cDNA sequences:
(6) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for PRKAG3 Gene

Protein kinase, AMP-activated, gamma 3 non-catalytic subunit:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for PRKAG3 Gene

No ASD Table

Relevant External Links for PRKAG3 Gene

GeneLoc Exon Structure for
PRKAG3
ECgene alternative splicing isoforms for
PRKAG3

Expression for PRKAG3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for PRKAG3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PRKAG3 Gene

This gene is overexpressed in Muscle - Skeletal (x47.0).

NURSA nuclear receptor signaling pathways regulating expression of PRKAG3 Gene:

PRKAG3

SOURCE GeneReport for Unigene cluster for PRKAG3 Gene:

Hs.591634

mRNA Expression by UniProt/SwissProt for PRKAG3 Gene:

Q9UGI9-AAKG3_HUMAN
Tissue specificity: Skeletal muscle, with weak expression in heart and pancreas.

Evidence on tissue expression from TISSUES for PRKAG3 Gene

  • Muscle(4.7)
genes like me logo Genes that share expression patterns with PRKAG3: view

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for PRKAG3 Gene

Orthologs for PRKAG3 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for PRKAG3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PRKAG3 33 34
  • 99.32 (n)
cow
(Bos Taurus)
Mammalia PRKAG3 33 34
  • 87.43 (n)
dog
(Canis familiaris)
Mammalia PRKAG3 33 34
  • 86.24 (n)
mouse
(Mus musculus)
Mammalia Prkag3 16 34 33
  • 85.31 (n)
rat
(Rattus norvegicus)
Mammalia Prkag3 33
  • 83.81 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia PRKAG3 34
  • 79 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia PRKAG3 34
  • 71 (a)
OneToOne
chicken
(Gallus gallus)
Aves PRKAG3 33 34
  • 75.6 (n)
lizard
(Anolis carolinensis)
Reptilia PRKAG3 34
  • 71 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia prkag3 33
  • 70.04 (n)
African clawed frog
(Xenopus laevis)
Amphibia prkag3-prov 33
zebrafish
(Danio rerio)
Actinopterygii prkag3b 33 34
  • 64.74 (n)
prkag3a 34
  • 62 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta SNF4Agamma 35 34
  • 53 (a)
worm
(Caenorhabditis elegans)
Secernentea Y111B2A.8 35
  • 49 (a)
T20F7.6 35
  • 37 (a)
Y41G9A.3 35
  • 32 (a)
aakg-1 34
  • 30 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SNF4 34
  • 34 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.7193 34
  • 45 (a)
OneToMany
Species where no ortholog for PRKAG3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for PRKAG3 Gene

ENSEMBL:
Gene Tree for PRKAG3 (if available)
TreeFam:
Gene Tree for PRKAG3 (if available)

Paralogs for PRKAG3 Gene

Paralogs for PRKAG3 Gene

(2) SIMAP similar genes for PRKAG3 Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with PRKAG3: view

Variants for PRKAG3 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for PRKAG3 Gene

AAKG3_HUMAN-Q9UGI9
PRKAG3 genetic variants can be associated with increased glycogen content in skeletal muscle [MIM:604976]. Muscle fibers from carriers of variant Trp-225 have approximately 90% more muscle glycogen content than controls and decreased levels of intramuscular triglyceride.

Sequence variations from dbSNP and Humsavar for PRKAG3 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs138130157 Pathogenic 218,828,561(+) TGCCC(A/G)CACAC reference, missense
rs367916025 Uncertain significance 218,827,847(+) TCTCA(A/G)TCTTA reference, missense
rs370008874 Uncertain significance 218,828,560(+) CTGCC(A/C/T)GCACA reference, missense
rs371222838 Uncertain significance 218,830,303(+) CAGGA(C/T)CAGCT reference, missense
rs372752820 Uncertain significance 218,830,073(+) GGCGC(C/T)GGGTT reference, missense

Structural Variations from Database of Genomic Variants (DGV) for PRKAG3 Gene

Variant ID Type Subtype PubMed ID
nsv528407 CNV loss 19592680
nsv1131550 CNV deletion 24896259

Variation tolerance for PRKAG3 Gene

Residual Variation Intolerance Score: 44.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.63; 78.25% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for PRKAG3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PRKAG3

Disorders for PRKAG3 Gene

Relevant External Links for PRKAG3

Genetic Association Database (GAD)
PRKAG3
Human Genome Epidemiology (HuGE) Navigator
PRKAG3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
PRKAG3

No disorders were found for PRKAG3 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for PRKAG3 Gene

Publications for PRKAG3 Gene

  1. Gain-of-function R225W mutation in human AMPKgamma(3) causing increased glycogen and decreased triglyceride in skeletal muscle. (PMID: 17878938) Costford SR … Harper ME (PloS one 2007) 3 4 22 60
  2. A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle. (PMID: 10818001) Milan D … Andersson L (Science (New York, N.Y.) 2000) 2 3 4 60
  3. Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program. (PMID: 20682687) Jablonski KA … Diabetes Prevention Program Research Group (Diabetes 2010) 3 45 60
  4. Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study. (PMID: 20800603) Flachsbart F … Nebel A (Mutation research 2010) 3 45 60
  5. Physiogenomic comparison of edema and BMI in patients receiving rosiglitazone or pioglitazone. (PMID: 18996102) Ruaño G … Hanks S (Clinica chimica acta; international journal of clinical chemistry 2009) 3 45 60

Products for PRKAG3 Gene

Sources for PRKAG3 Gene

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