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FLASH GENE
Symbol PICK1 contributors: mct/pgu - updated : 13-09-2016
HGNC name protein interacting with PRKCA 1
HGNC id 9394
Location 22q13.1      Physical location : 38.453.261 - 38.471.707
Synonym name
  • protein interacting with C kinase 1 (and ARF)
  • protein kinase C, alpha binding protein
  • Synonym symbol(s) PRKCABP, dJ1039K5, MGC15204, PICK
    DNA
    TYPE functioning gene
    STRUCTURE 18.45 kb     13 Exon(s)
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 2224 46 415 - 2007 17914463
    13 - 2126 46 415 - 2007 17914463
    differs in the 5' UTR compared to variant 1
    12 - 2073 46 415 - 2007 17914463
    differs in the 5' UTR compared to variant 1
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen   highly
    Reproductivemale systemtestis  highly Homo sapiens
    Urinarybladder   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    not specificepithelial cell
    Reproductivespermatid Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a single PDZ-BAR-domain known to mediate interaction with the C termini of several receptors, transporters, ion channels, and kinases
  • a region homologous to arfaptin 1 and 2
  • mono polymer homomer , monomer , dimer
    HOMOLOGY
    interspecies ortholog to murine Prkcabp
    ortholog to rattus Prkcabp
    Homologene
    FAMILY
  • PRK family
  • CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,adherens
        intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,granule
    intracellular,cytoplasm,cytoskeleton
    text
  • concentrated in perinuclear region and in excitatory synapses
  • localised at adherens junctions in epithelial cells
  • diffuse cytoplasmic localization, but it clusters on vesicle-like structures that colocalize with the trans-Golgi network marker TGN38 upon deletion of either the ACT or PDZ domain
  • localise to the Golgi apparatus and the proacrosomal granules that are transported in the acrosome
  • basic FUNCTION
  • Ca2+-binding protein, that may function as an adaptor that binds to and organizes the subcellular localization of a variety of membrane proteins
  • acting as an anchoring protein that specifically targets PRKCA to mitochondria in a ligand-specific manner
  • protein kinase binding protein, potentially involved in vesicular trafficking
  • playing an essential role in the control of synaptic transmission by GRM7
  • may regulate ACCN3-ACCN2 heteromeric cation channel
  • involved in the clustering of various receptors, possibly by acting at the receptor internalization level
  • could be involved in the regulation of both adherens and tight junctions in epithelial cells
  • postsynaptic Ca2+-binding protein that provides a direct mechanistic link between N-methyl-D-aspartate receptor-mediated Ca2+ influx and AMPAR endocytosis
  • inhibiting potently Arp2/3-mediated actin polymerization
  • being critical for a specific form of vesicle trafficking, and also for the development of neuronal architecture
  • plays a crucial role in the response to oxygen and glucose deprivation that results in altered synaptic transmission and neuronal death
  • having a role in synaptic plasticity established most clearly in the cerebellum, where long-term depression at multiple synapses requires intact PICK1 function
  • its function is specific to NMDAR-dependent long-term depression(LTD) and the underlying AMPAR trafficking
  • implicated in the regulation of AMPAR trafficking underlying several forms of synaptic plasticity, and is essential for the intracellular retention of AMPA receptors underlying long-term depression
  • AMPA-type glutamate receptors (AMPARs) mediate the majority of fast excitatory neurotransmission in the mammalian central nervous system
  • developmentally regulated role for PICK1 in hippocampal synaptic plasticity and learning, and in normal brain function
  • regulates spine size in hippocampal neurons via inhibition of the Arp2/3 complex
  • functions as a crucial factor in both structural and functional plasticity
  • important role of PICK1 in inactivity-induced synaptic scaling by regulating the subunit composition, abundance, and trafficking of GluA2-containing AMPARs
  • KIRREL, KIRREL2, KIRREL3 and PICK1 synergistically regulate cell recognition and contact formation
  • non-neural function of PICK1 is an important negative regulator of TGFB1 signaling
  • may not only affect glutamatergic neurotransmission by its regulatory effect on glutamate receptors but may also affect neuronal excitability via an increased SLC2A1-mediated leak current
  • is involved in regulating the cell-cell junction in epithelial cells, and this may influence therapeutic strategy decisions with regards to cell adhesion molecules in metastatic disease
  • functions in vesicle biogenesis and is necessary to maintain normal vesicle numbers and size
  • modular scaffold implicated in synaptic receptor trafficking
  • is crucial for vesicle trafficking, and its deficiency in sperm cells leads to abnormal vesicle trafficking from the Golgi to the acrosome
  • PDZ domain-containing protein, known to increase the reuptake activities of dopamine transporters by increasing their expressions on the cell surface
  • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS development
    text development of neuronal architecture
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with GRM7
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to GTP-bound forms of ARFA/ARF3 and ARF1
  • binding to the short alternative splice variant of AMPA receptor
  • interacting with third PDZ domain of DLG2 (PDZ domains are protein-protein interaction modules that generally bind to the C termini of their target proteins)
  • parkin substrate (binds PICK1 via a PDZ-mediated interaction, which predominantly promotes PICK1 monoubiquitination rather than polyubiquitination)
  • ERBB2, EPHA7, EPHB1, EPHB2, PRKCA
  • interacting with SLC6A2 and SLC6A3
  • interacting with ACCN1 and ACCN2
  • interacting with BTG2, with GRIA2, GRIA3, the isoform A of GRM4, GRM7 and GRM8 and with NAPA and NAPB
  • interacting with UNC5A, CXADR
  • interacts directly with Nectins in a DLG4 domain-dependent manner
  • binds the AMPAR GLUR2 subunit and is involved in AMPAR internalisation
  • interacting with GRM7
  • binding filamentous (F)-actin and the actin-nucleating Arp2/3 complex
  • KLHL24 interacts with PICK1 in heterologous cells
  • PRKCA and PICK1 are NPHS1-binding proteins
  • KIRREL-interacting protein
  • via its C terminus, TSPAN7 interacts with the PDZ domain of PICK1, to regulate PICK1 and GluR2/3 association and AMPA receptor trafficking
  • interaction between PICK1 and PACSIN1 is regulated by PACSIN1 phosphorylation within the variable region and is required for AMPAR endocytosis
  • ability of SORCS3 to functionally interact with PICK1, an adaptor that sorts glutamate receptors at the postsynapse
  • PICK1 is the first DHHC8 substrate required for a specific form of synaptic plasticity
  • GRIA2-PICK1 interactions are a key component of the effects of APP on synapses
  • PICK1 binds RAC1 and CDC42, via distinct but overlapping binding sites
  • ICA1L is expressed in testes and brain, and is the major binding partner for PICK1 in testes
  • PICK1 mediates vesicle trafficking by interacting with GOLSYN, a kinesin-binding protein that mediates the trafficking of both synaptic vesicles and mitochondria in axons
  • in the central nervous system (CNS), PICK1 interacts with numerous neurotransmitters receptors, transporters, ion channels, and enzymes, and controls their trafficking
  • both ASIC1 and calcineurin have been shown to interact with the scaffolding protein PICK1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    defects in parkin-mediated PICK1 monoubiquitination could enhance ACCN2 activity and thereby promote neurodegeneration in Parkinson disease
    constitutional germinal mutation      
    cause globozoospermia, a male infertility disorder
    Susceptibility
    Variant & Polymorphism
    Candidate gene may play a role in the pathogenesis of schizophrenia
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    FSC231 inhibitor of PICK1 might serve as a lead in the future development of new therapeutics against neuropathic pain
    psychiatry  
    FSC231 inhibitor of PICK1 might serve as a lead in the future development of new therapeutics against excitotoxicity, depression and cocaine addiction
    diabetetype 1 
    PRKCA and PICK1 are promising therapeutic targets for diabetic nephropathy
    ANIMAL & CELL MODELS
  • of the mGluR7a-PICK1 complex is sufficient to induce absence epilepsy-like seizures in rats and mouse
  • loss of Pick1 has no significant effect on synaptic plasticity in juvenile mice but impairs some forms of long-term potentiation and multiple distinct forms of long-term depression in adult mice