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FLASH GENE
Symbol AKAP5 contributors: mct/shn - updated : 15-09-2015
HGNC name a kinase (PRKA) anchor protein 5
HGNC id 375
Location 14q23.3      Physical location : 64.932.216 - 64.941.220
Synonym name
  • A-kinase anchor protein 5
  • A-kinase anchor protein 79 kDa
  • A-kinase anchor protein, 79kDa
  • A-kinase anchoring protein 75/79
  • AKAP 79
  • AKAP-5
  • OTTHUMP00000174435
  • cAMP-dependent protein kinase regulatory subunit II high affinity binding protein
  • cAMP-dependent protein kinase regulatory subunit II high affinity-binding protein
  • Synonym symbol(s) AKAP75, AKAP79, DAKAP1, H21, AKAP79/150, AKAP150
    DNA
    TYPE functioning gene
    STRUCTURE 9.01 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure intronless
    MAPPING cloned Y linked N status provisional
    Map cen - D14S63 - D14S1026 - AKAP5 - D14S982 - D14S271 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 6487 47.1 427 - 2007 17548344
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen    
    Nervousbrainforebraincerebral cortex predominantly
     braindiencephalonhypothalamus  
    Reproductivefemale systembreastmammary gland  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a positively charged N terminus for association with the cytoskeleton and for intracellular membrane
  • a C terminal region binding of RIIbeta
  • secondary structure an amphipathic helix binding domain
    mono polymer dimer
    HOMOLOGY
    interspecies ortholog to AKAP5, Mus musculus
    ortholog to Akap5, Rattus norvegicus
    ortholog to AKAP5, Pan troglodytes
    Homologene
    FAMILY
  • A-kinase anchor proteins
  • CATEGORY chaperone/stress , structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    text
  • associated with post synaptic densities at the inner surface of excitating synapses just inside the post synaptic membrane
  • remains associated with its G-protein-coupled receptor, at the cell membrane, docked with the receptor during agonist-induced internalization
  • localized to the plasma membrane (PM) through an N-terminal targeting domain consisting of three polybasic subdomains
  • its localization in lipid rafts is required for the phosphorylation of ADCY8 and regulation of Ca2+-dependent ADCY8 activity
  • basic FUNCTION
  • coordinates the location of the cAMP-dependent protein kinase, calcineurin, and protein kinase C (PKC) at the postsynaptic densities in neurons
  • a kinase (PRKA regulatory subunits RIA, RIIA, PKC) anchor protein, tethering the enzyme near its physiological substrate
  • involved in the regulation of postsynaptic events
  • multivalent signaling scaffold that binds the cAMP-dependent protein kinase (PKA), the Ca2+-dependent phosphatase calcineurin (CaN or PP2B), and PKC
  • acts as a key regulator in the two cAMP pathways to control AKT1 phosphorylation
  • function in switching signaling pathways of the receptor from adenylylcyclase to activation of the mitogen-activated protein kinase cascade
  • required for NMDA receptor-dependent long-term depression
  • provides a platform for dynamic PKA regulation of KCND2 expression, fundamentally impacting CA1 excitability
  • acts as a PPP1 regulatory subunit that can direct PPP1 activity toward specific targets in the AKAP5 complex
  • palmitoylation/depalmitoylation cycle of a key regulatory protein, such as AKAP5, can have important consequences for fine-tuning signaling transduction pathways mediated by key effector proteins that bind AKAP5
  • anchored signalling events that facilitate insulin secretion and glucose homeostasis may be set by AKAP5 associated phosphatase activity
  • significant role for the AKAP5 scaffold in signaling and trafficking of the ADRB1 in cardiac myocytes and mammalian cells
  • likely AKAP5, PRKCA, and TRPV4 channels form dynamic subcellular signaling domains that control Ca(2+) influx into arterial myocytes
  • GPER1 forms a plasma membrane complex with a membrane-associated guanylate kinase and AKAP5
  • is a component of the postsynaptic density in neurons and plays a vital role in modulating neuronal activities
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • ADCY5 and ADCY6 interact with-A-kinase anchoring protein AKAP5 in a complex which associates with PRKACA
  • PRKACA, AKT1 and RAPGEF3 were all shown to establish complexes with neuronal A-kinase anchoring protein 150 (AKAP5)
  • dimeric AKAP5 coordinates two RII 1–45 homodimers, four PP2B heterodimers, and two CALM1 molecules
  • AKAP5 and AKAP12 are capable of forming hetero-oligomeric supermolecular complexes that influence AKAP locale and function
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • protein phosphatase 2B, PP2Bbeta and calcineurin, CaN
  • calmodulin with high affinity in a Ca2+-dependent manner
  • potassium inwardly-rectifying channel, subfamily J, member 2, KCNJ2
  • beta1 and beta3 of GABA(A) receptor
  • IQ motif containing GTPase activating protein 1, IQGAP1
  • interacts with ADCY8 and regulates Ca2+-dependent cAMP synthesis in pancreatic and neuronal system
  • interacts with KCND2 complexes and the two proteins colocalize in hippocampal neurons
  • binding of Ca2+/CALM1 to AKAP5 generates an additional PP2B interaction site on the anchoring protein to activate the tethered phosphatase
  • CALM1 associated with AKAP5 is able to activate anchored PP2B within the same signaling complex
  • novel PPP1 regulatory subunit
  • directly bind to adenylyl cyclase type 8 (ADCY8) and regulate its responsiveness to store-operated Ca2+ entry (SOCE)
  • CALM1 is a known interaction partner of AKAP5 that has been shown to regulate activity of the kinase PKC in a Ca(2+) -dependent manner
  • AKAP5 can interact with CABP1, a neuronal calcium-binding protein implicated in regulation of Ca(2+) -influx and release
  • direct anchoring of both PRKACA and ADCY1 to TRPV1 by AKAP5 facilitates the response to inflammatory mediators and may be critical in the pathogenesis of thermal hyperalgesia
  • anchoring of not only PRKACA but also ADCY1 by AKAP5 is important for regulation of postsynaptic functions and specifically AMPA receptor activity
  • the extreme C-terminus of ADRB1 binds DLG1 and AKAP5 to organize a scaffold involved in trafficking of the ADRB1
  • a key region on AKAP79, between AAs 326-336, is responsible for its interaction with TRPV1
  • GPER1 interacted with membrane-associated guanylate kinases, including DLG1 and DLG4, and protein kinase A-anchoring protein (AKAP5) in the plasma membrane in a PDZ-dependent manner
  • cell & other
    REGULATION
    Other palmitoylated via two cysteines in its N-terminal region, and this palmitoylation plays a key role in targeting the AKAP5 to lipid rafts
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    gene silencing reduces basal phosphorylation of TRPV1
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    antagonizing the TRPV1-AKAP5 interaction will be a useful strategy for inhibiting inflammatory hyperalgesia
    ANIMAL & CELL MODELS
  • loss of AKAP150 in mice is associated with an exclusion of the PKA holoenzyme from hippocampal dendritic spines, changes in synaptic transmission and deficits in memory retention. AKAP150-/- mice display behavioral defects associated with perturbed cerebellar function
  • functional studies in neurons isolated from AKAP150-/- mice indicate that the anchoring protein is not required for pharmacological desensitization of TRPV1 (