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FLASH GENE
Symbol PIK3C3 contributors: mct/ - updated : 07-03-2015
HGNC name phosphoinositide-3-kinase, class 3
HGNC id 8974
Location 18q12.3      Physical location : 39.535.198 - 39.661.444
Synonym name
  • vacuolar protein sorting 34 (yeast)
  • PtdIns-3-kinase type 3
  • phosphatidylinositol 3-kinase p100 subunit
  • PI3-kinase type 3
  • Synonym symbol(s) VPS34, MGC61518
    EC.number 2.7.1.137
    DNA
    TYPE functioning gene
    STRUCTURE 126.25 kb     25 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    BRUNOL4 18q12 bruno-like 4, RNA binding protein (Drosophila) LOC388474 18 similar to 60S ribosomal protein L7a (Surfeit locus protein 3) (PLA-X polypeptide) NPM1P1 18q12.3 nucleophosmin 1 (nucleolar phosphoprotein B23, numatrin) pseudogene 1 PIK3C3 18q12.3 phosphoinositide-3-kinase, class 3 LOC284260 18q12.3 hypothetical gene supported by BC011527; BC021928; BC011527; BC021928 RIT2 18q12.3 Ras-like without CAAX 2 SYT4 18q12.3 synaptotagmin IV LOC342732 18q21.1 similar to cytokeratin 8 LOC388475 18 LOC388475 SETBP1 18q21.1 SET binding protein 1 SLC14A2 18q12.1-q21.1 solute carrier family 14 (urea transporter), member 2 SLC14A1 18q12 solute carrier family 14 (urea transporter), member 1 (Kidd blood group) LOC284266 KIAA1632 18q21.1 KIAA1632 protein PSTPIP2 18q12 proline-serine-threonine phosphatase interacting protein 2 ATP5A1 18q12-q21 ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit, isoform 1, cardiac muscle LOC115106 MGC12909 18q21.1 hypothetical protein MGC12909 FLJ34218 18q21.1 hypothetical protein FLJ34218 FLJ32670 18q21.1 hypothetical protein FLJ32670
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 - 3083 101.42 887 - 1995 7628435
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Urinarykidneynephronrenal capsuleglomerulus  Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Urinarypodocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • PIK domain
  • C2 domain
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to yeast vps34
    Homologene
    FAMILY
  • PI3/PI4-kinase family
  • CATEGORY enzyme , signaling , receptor membrane , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • phosphorylating phosphoinositide
  • regulates both the endosomal and autophagic pathways
  • specifically catalyzes the formation of phosphatidylinositol-3-phosphate (PI3P)
  • essential for neuronal integrity and survival
  • plays important roles in the endocytic and autophagic pathways, both of which are essential for maintaining neuronal integrity
  • phosphatidylinositol 3-kinase class III sub-complex containing PIK3R4, PIK3C3, BECN1, UVRAG and SH3GLB1 regulates cytokinesis and degradative endocytic traffic
  • regulate various intracellular membrane trafficking events
  • plays an essential role in regulating functional autophagy and is indispensable for normal liver and heart function
  • is necessary for autophagic flux in the heart, and PIK3C3 ablation leads to heart failure and death
  • essential role of PIK3C3 in regulating autophagy, and liver and heart function
  • is required for the maintenance of na
  • ve T cells, acting in a cell-intrinsic manner
  • PIK3C3-dependent canonical autophagy plays a critical role in maintaining T-cell homeostasis by promoting T-cell survival through quality control of mitochondria
  • is a major regulator of endolysosomal pathways in podocytes, suggesting the fundamental roles of endocytosis and fluid-phase uptake for the maintenance of the glomerular filtration barrier
  • indispensable role for PIK3C3 in the regulation of intracellular vesicle trafficking and processing to protect the normal cellular metabolism, structure and function of podocytes
  • activity of the PIK3C3/PIK3R4 complex is critical in disease conditions such as autophagic vacuolar myopathy (AVM), and possibly a variety of other lysosomal storage diseases
  • plays a critical role in intracellular membrane trafficking and autophagy induction
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    text diversion of proteins from the secretory pathway to vacuoles
    PATHWAY
    metabolism
    signaling signal transduction
  • PIK3C3-PLD1 pathway acts independently of, and in parallel to, the Rag pathway in regulating amino acid activation of MTOR
  • a component
  • component of a complex with PIK3R4
  • part of the BECN1-PIK3C3 complex that regulate APP processing and play an important role in Alzheimer Disease pathology
  • forms multiple complexes and the ATG14-containing PIK3C3 is specifically involved in autophagy induction
  • BECN1/PIK3C3 complex plays a crucial role in autophagosome formation
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PIK3R4
  • BECN1 coiled coil domain (CCD) serves as an interaction platform for assembly of distinct ATG14- and UVRAG-containing complexes to modulate PIK3C3 activity
  • SLAMF1 interacts with the class III PIK3C3 in a complex with BECN1 and UVRAG
  • SLAMF1 recruits a subset of PIK3C3-associated proteins, which is involved in membrane fusion and CYBB regulation
  • DEDD interacts with PI3KC3 to activate autophagy and attenuate epithelial-mesenchymal transition in human breast cancer
  • ATG14 dictates the differential regulation (either inhibition or activation) of different PIK3C3 complexes in response to glucose starvation
  • AMPK directly phosphorylates PIK3C3 and BECN1 to regulate non- and pro-autophagic PIK3C3 complexes, respectively
  • WASH1 can suppress BECN1 ubiquitination to inactivate PIK3C3 activity leading to suppression of autophagy
  • PRNP interacts with BECN1 to recruit the PIK3C3 complex into lipid rafts and thus activates autophagy in response to Abeta42, defining a novel role of PRNP in the regulation of autophagy
  • DACT1 enhances the ATG14-BECN1-PIK3C3 complex formation and PIK3C3 kinase activity
  • NRBF2 may interact with the ATG14-containing BECN1-PIK3C3 protein complex to modulate protein-protein interactions within the complex, leading to suppression of PIK3C3 activity, autophagosome biogenesis, and autophagic flux
  • GADD45A inhibits autophagy via impairing the BECN1-PIK3C3 complex formation
  • at the Golgi, PIK3R4 and GOLGA2 form a protein complex devoid of PIK3C3 to ensure the IFT20-dependent sorting and transport of membrane proteins from the cis-Golgi to the primary cilium
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    results in neurodegeneration because of drastic defects in the endo-lysosomal pathways
    Susceptibility to schizophrenia and bipolar diseases
    Variant & Polymorphism other polymorphism in the promoter region was associated with schizophrenia and bipolar diseases
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    systemic use of PIK3C3 inhibitors as anticancer drugs may have serious side effects
    ANIMAL & CELL MODELS
  • Mtor signaling is drastically reduced in Pik3c3 null embryos, which could be a major contributor to the observed proliferation and embryogenesis defects
  • in mice, podocyte-specific conditional knockout of Vps34 led to early proteinuria, glomerular scarring, and death within 3-9 weeks of age