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FLASH GENE
Symbol PDE10A contributors: mct - updated : 29-04-2016
HGNC name phosphodiesterase 10A
HGNC id 8772
RNA
TRANSCRIPTS type messenger
text
  • without/with a phosphorylation site respectively
  • 12 splice variants characterized by unique N- and C-terminal sequences have been described (PMID: 22105073)
    • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 splicing 8189 89.4 789 - 2006 16330539
    23 splicing 8317 - 779 - 2001 14604994
  • N-terminus having a putative phosphorylation site by cAMP-dependent protein kinase (cAK)
  • phosphorylation at Thr16 by PKA caused alteration of subcellular localization of PDE10A2 from the Golgi apparatus to cytosol
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
     brainbasal nucleiputamen  Homo sapiens
    Nervousbrainbasal nucleicaudate nucleus  Homo sapiens
     brainbasal nucleistriatum predominantly Homo sapiens
    Reproductivemale systemtestis  highly Homo sapiensmRNA
    Visualeyeretina    Rattus norvegicus
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    Visualcone photoreceptor Rattus norvegicus
    Visualrod photoreceptor Rattus norvegicus
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a single N terminal putative cGMP binding sequence, and a tandem of so-called GAF domains in its N-terminal regulatory regions , and this two N-terminal domains, GAF-A and GAF-B, of which the latter binds to cAMP
  • a C terminal catalytic domain
    • HOMOLOGY
    Homologene
    FAMILY
  • cyclic nucleotide phosphodiesterase family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    text
  • cAMP signaling in the Golgi area and the cytosol in neurons is controlled through alteration of subcellular localization of PDE10A brought by activation of PKA in response to intracellular elevations of cAMP
  • most often associated with membranes in dendrites and spines
    • basic FUNCTION
  • exhibiting unique kinetic properties and inhibitor sensitivity
  • playing a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides
  • may have a role in the pain pathway of migraine as well as trigeminal neuralgia and trigeminal autonomic cephalalgias
  • potential role of PDE10A in the adaptation of cyclic nucleotide signaling to daily changes in light intensity in retinal neurons including photoreceptors
  • is potently stimulated by cAMP, and the GAF-mediated stimulation alters the enzymatic parameters such that the enzyme acts as a cAMP-specific phosphodiesterase
  • plays a pivotal role in striatal signaling and striatum-mediated salience attribution
  • critical role of PDE10A in motor control
  • contributes to the regulation of the intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
    cell & other
    REGULATION
    activated by cAMP, is the only PDE activated by cAMP
    inhibited by by the non-specific PDE inhibitor, IBMX
    by cGMP
    Other phosphorylation of PDE10A has an impact on the interaction with other signaling proteins and adds an additional line of complexity to the role of PDE10A in regulation of synaptic transmission
    ASSOCIATED DISORDERS
    corresponding disease(s) COCBS
    Susceptibility to hyperthyrotropinaemia (and possibly hypothyroidism)
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologydystonia 
    pharmacological manipulation of cAMP levels in striatal medium spiny neurons (MSNs), is a promising therapeutic strategy for the treatment of chorea and other movement disorders
    ANIMAL & CELL MODELS