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FLASH GENE
Symbol PRKAA1 contributors: mct - updated : 07-06-2016
HGNC name protein kinase, AMP-activated, alpha 1 catalytic subunit
HGNC id 9376
Location 5p13.1      Physical location : 40.759.481 - 40.798.297
Synonym name
  • AMPK, alpha-1 chain
  • 5'-AMP-activated protein kinase, catalytic alpha-1 chain
  • Synonym symbol(s) AMPKA1, AMPK, AMPK1, MGC33776, MGC57364
    EC.number 2.7.11.1/2.7.11.26/2.7.11.27
    DNA
    TYPE functioning gene
    STRUCTURE 38.82 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    GDNF 5p13-p12 glial cell derived neurotrophic factor FLJ39155 5p13.2 hypothetical protein FLJ39155 LIFR 5p13-p12 leukemia inhibitory factor receptor LOC253254 5p13.2 hypothetical LOC253254 OSMR 5p13.2 oncostatin M receptor KIAA1999 MGC39830 5p13.2 hypothetical protein MGC39830 FYB 5p13.1 FYN binding protein (FYB-120/130) C9 5p13 complement component 9 DAB2 5p13-p12.1 disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila) LOC285634 5p13.2 similar to DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 26; RNA helicase HDB; deleted in cancer 1; RNA helicase HDB/DICE1; DEAD box protein LOC389285 5 LOC389285 PTGER4 5p13.1 prostaglandin E receptor 4 (subtype EP4) OSRF 5p15.2-p12 osmosis responsive factor PRKAA1 5p14-p11 protein kinase, AMP-activated, alpha 1 catalytic subunit LOC389286 5 similar to FKSG62 RPL37 5p13-p12 ribosomal protein L37 CARD6 5p12 caspase recruitment domain family, member 6 C7 5p13 complement component 7 FLJ40243 5p13.1 hypothetical protein FLJ40243 C6 5p13 complement component 6 LOC345557 5p13.1 similar to RIKEN cDNA B130016O10 gene TCP1L2 5pter-p15.32 t-complex 1-like 2 OXCT 5p13 3-oxoacid CoA transferase LOC285636 5p13.1 hypothetical protein LOC285636 FBXO4 5p12 F-box only protein 4 LOC391779 5 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) GHR 5p13.1-p12 growth hormone receptor LOC389287 5 similar to synaptonemal complex protein SYP-1, SYnaPsis in meiosis abnormal SYP-1 (56.6 kD) (syp-1) SEPP1 5q31 selenoprotein P, plasma, 1 LOC391780 5 similar to peptidyl-Pro cis trans isomerase LOC340065 5p13.1 hypothetical LOC340065 LOC389288 5 LOC389288 LOC389289 5 similar to annexin II receptor LOC153684 5p13.1 hypothetical protein LOC153684 FLJ90723 5p13.1 hypothetical protein FLJ90723 FLJ10246 5p13.1 hypothetical protein FLJ10246 MGC42105 5p13.1 hypothetical protein MGC42105 HMGCS1 5p14-p13 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (soluble) CCL28 5p12 chemokine (C-C motif) ligand 28 FLJ21657 5p12 hypothetical protein FLJ21657 FLJ32363 5p12 FLJ32363 protein PAIP1 5q31.1-q31.3 Homo sapiens polyadenylate binding protein-interacting protein 1 (PAIP1), transcript variant 3, mRNA. NNT 5p13.1-cen nicotinamide nucleotide transhydrogenase
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 5085 64 559 - 1996 9224708
    10 - 5130 65.4 574 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   moderately
    Digestiveesophagus   moderately
     mouthtongue  moderately
    Endocrineparathyroid   highly
    Hearing/Equilibriumear   moderately
    Nervousnerve   moderately
    Reproductivemale systemtestis  moderately
    Respiratoryrespiratory tractlarynx  moderately
     respiratory tracttrachea  predominantly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  moderately
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    conjugated PhosphoP
    mono polymer heteromer , trimer
    HOMOLOGY
    interspecies ortholog to rattus Prkaa1 (99.1pc)
    ortholog to murine Prkaa1 (98.7pc)
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • SNF1 subfamily
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • responsible for the regulation of fatty acid synthesis by phosphorylation of acetyl-CoA carboxylase
  • regulating cholesterol synthesis via phosphorylation and inactivation of hormone-sensitive lipase and hydroxymethylglutaryl-CoA reductase
  • energy-sensing enzyme believed to be a critical regulator of glucose and fat metabolism in skeletal muscle during exercise
  • appearing to act as a metabolic stress-sensing protein kinase switching off biosynthetic pathways when cellular ATP levels are depleted and when 5'-AMP rises in response to fuel limitation and/or hypoxia
  • heterotrimeric protein complex that responds to the cellular energy status by switching off ATP-consuming pathways and switching on ATP-generating pathways when ATP is limiting
  • acting as a cAMP-dependent protein kinase
  • acting as an eukaryotic elongation factor-2 kinase activator
  • involved in the activation of MAPK
  • had no role in oxidative stress-induced breakdown of RPE barrier function
  • involved in the pathogenesis of Alzheimer disease
  • critical roles in regulating growth and reprogramming metabolism, and has recently been connected to cellular processes such as autophagy and cell polarity
  • in addition to its function in ATP homeostasis, has a key function in NADPH maintenance, which is critical for cancer cell survival under energy stress conditions
  • maintain intracellular ATP level under conditions of energy stress
  • is critical for cancer cell survival during metabolic stress, which can occur in the solid tumour microenvironment
  • mediates spindle pole-associated MYL2(ser19) to control spindle orientation via regulation of actin cortex-astral microtubule attachments
  • PRKAA1-dependent autophagy-mediated clearance of damaged mitochondria is required for erythrocyte maturation and homeostasis
  • may play a role in the Hh signaling pathway, through which it regulates tumorigenesis
  • PRKAA1 and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest
  • is a key mediator linking obesity and impaired muscle regeneration
  • play roles in regulating various cellular processes such as mitochondrial biogenesis
  • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    text positive regulation of anti-apoptosis
    PATHWAY
    metabolism lipid/lipoprotein
    signaling signal transduction
    fatty acid biosynthesis (positive regulation of fatty acid oxidation)
  • cholesterol biosynthesis (positive regulation)
  • steroid biosynthesis
  • sterol biosynthesis
  • negative regulation of glucosylceramide biosynthesis
  • negative regulation of protein biosynthesis
  • positive regulation of gluconeogenesis
  • positive regulation of glucose import
  • a component
  • heterotrimer of a catalytic subunit (alpha), a beta and a gamma non-catalytic subunits
  • catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK)
  • autophosphorylated
  • INTERACTION
    DNA
    RNA
    small molecule cofactor, nucleotide,
  • ATP
  • cAMP
  • regulated by NME1 independently of the AMP concentration such that the manipulation of NME1 nucleotide trans-phosphorylation activity to generate ATP enhanced the activity of PRKAA1
  • protein
  • interacting with SPARC (SPARC may be involved in regulating glucose metabolism via PRKAA1 activation)
  • PRKAA1, PRKAG1, PRKAB1 association with ULK1 plays an important role in autophagy induction, at least in part, by phosphorylation of raptor to lift the inhibitory effect of MTOR on the ULK1 autophagic complex
  • CRBN directly interacts with the alpha1 subunit of AMP-activated protein kinase (PRKAA1) and inhibits the activation of AMPK activation
  • PRKAA1 might regulate NADPH homeostasis by inhibiting ACACA and ACACB
  • PRKAA1-mediated inhibition of ACACA is required to maintain the NADPH and reactive oxygen species levels after matrix detachment
  • renin synthesis and secretion are regulated by PRKAA1 and coupled to metabolism by phosphorylation of ACACA
  • is required for IL10 activation of the PI3K/AKT1/MTOR and STAT3-mediated anti-inflammatory pathways regulating macrophage functional polarization
  • PRKAA1 stimulates ubiquitination of the gap junction protein GJA1, thereby contributing to gap junction remodeling following pressure overload
  • PDLIM5 is a novel PRKAA1 substrate and it plays a critical role in the inhibition of cell migration
  • reciprocal regulation of GPLD1 by PRKAA1 and regulation of PRKAA1 by GPLD1 and phosphatidic acid (PA)
  • FNDC5 plays an important role in glucose metabolism via the ROS-mediated PRKAA1 pathway in skeletal muscle cells
  • MAP3K11 serves as a common upstream kinase of PRKAA1 and JNK and functions as a direct upstream kinase for PRKAA1 independent of STK11
  • PRKAA1-dependent phosphorylation of ULK1 is critical for translocation of ULK1 to mitochondria and for mitophagy in response to hypoxic stress
  • regulation of DNM1L phosphorylation by PRKAA1 activation contributed to suppression of ER stress and thus presented a potential therapeutic strategy for PRKAA1 activation in the regulation of endothelium homeostasis
  • cell & other
    REGULATION
    activated by cAMP
    LEP in skeletal muscle
    metformin, phenformin, and the AMP mimetic, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR)
    inhibited by LEP in hypothalamus
    Other response to hypoxia
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    PRKAA1 activation, during energy stress, prolongs cell survival by redox regulation
    constitutional       gain of function
    activation of PRKAA1 plays a critical role in TARDBP mislocalization and the development of ALS
    tumoral     --low  
    is associated with poor survival in melanoma patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurosensorialvisual 
    PRKAA1 signaling pathway plays an important role in maintaining energy balance, and therefore may be a therapeutic target to prevent or delay retinal degeneration
    neurologyneurodegenerative 
    may be a potential drug target for ALS
    ANIMAL & CELL MODELS
  • prkaa1(-/-) mice manifest splenomegaly and anemia