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FLASH GENE
Symbol PIK3CA contributors: mct/npt/pgu - updated : 06-07-2015
HGNC name phosphoinositide-3-kinase, catalytic, alpha polypeptide
HGNC id 8975
Corresponding disease
CLOVES congenital lipomatous overgrowth, vascular malformations, and epidermal nevi syndrome
CWS5 Cowden syndrome 5
MCAP megalencephaly-capillary malformation-polymicrogyria syndrome
Location 3q26.32      Physical location : 178.866.310 - 178.952.495
Synonym name
  • PI3-kinase p110 subunit alpha
  • phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, alpha isoform
  • PtdIns-3-kinase p110
  • Synonym symbol(s) PI3K, p110-alpha, MGC142161, MGC142163, CLOVE, MCAP, MCM, MCMTC
    EC.number 2.7.1.137, 2.7.1.153
    DNA
    TYPE functioning gene
    STRUCTURE 86.18 kb     21 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure promoter transcriptionally silenced by the tumor suppressor protein TP53
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC339845 3q26.33 similar to argininosuccinate synthetase KCNMB2 3q26.3-q27.1 potassium large conductance calcium-activated channel, subfamily M, beta member 2 WIG1 3q26.3-q27 potassium large conductance calcium-activated channel, subfamily M, beta member 2 PIK3CA 3q26.3 phosphoinositide-3-kinase, catalytic, alpha polypeptide KCNMB3 3q26.3-q27.1 potassium large conductance calcium-activated channel, subfamily M beta member 3 ANC_2H01 3q27.1 zinc finger protein ANC_2H01 MFN1 3q27.1 mitofusin 1 GNB4 21q22.3 guanine nucleotide binding protein (G protein), beta polypeptide 4 BAF53A 3q27.1 guanine nucleotide binding protein (G protein), beta polypeptide 4 MRPL47 3q27.1 mitochondrial ribosomal protein L47 NDUFB5 3q27.1 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5, 16kDa USP13 3q26.2-q26.3 ubiquitin specific protease 13 (isopeptidase T-3) PEX5R 3q27.1 Pex5p-related protein LOC391593 3 similar to Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) (38 kDa BFA-dependent ADP-ribosylation substrate) (BARS-38) LOC131054 3q27.2 similar to RalA binding protein 1 (RalBP1) (Ral interacting protein 1) (76-kDa Ral-interacting protein) (Dinitrophenyl S-glutathione ATPase) (DNP-SG ATPase) TTC14 3q27.2 tetratricopeptide repeat domain 14 DKFZp434A128 3q27.2 hypothetical protein DKFZp434A128 LOC389178 3 similar to RING finger protein 13 LOC391594 3 similar to KIAA1552 protein LOC391595 3 similar to 60S ribosomal protein L32 FXR1 3q28 fragile X mental retardation, autosomal homolog 1 LOC131118
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 3724 124.3 1068 - 1994 7713498
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
     bone marrow  highly Homo sapiens
    Connectivebone  predominantly
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal adaptor binding domain (ABD)
  • a phosphotyrosine binding domain (PTB),
  • the p85 binding domain
  • a helical domain
  • a potential RAS-binding domain(RBD)
  • a membrane-binding C2 domain
  • mono polymer heteromer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • PI3/PI4-kinase family
  • CATEGORY enzyme , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • activating Akts in the antiapoptotic PIK3 pathway
  • regulator of cell growth and apoptosis
  • mediating angiogenesis and expression of VEGF in endothelial cells
  • function as an oncogene among anaplastic thyroid carcinomas and less frequently well-differentiated thyroid carcinomas
  • with PIK3CB, regulate S-phase entry
  • mediate oncogenic signalling induced by several oncogenes such as ERRB2 or RAS
  • plays a key role in insulin action and tumorigenesis
  • positively regulates the development and function of both osteoblasts and osteoclasts
  • critical for myofiber maturation and Z-disc alignment
  • regulates the expression of genes essential for cardiac structure and Z-disc signaling
  • is essential for clonal expansion, differentiation, and effector function of B and T lymphocytes
  • PIK3CA/AKT1, may be involved in the response to hypoxia of immature and, more specifically, of mature dendritic cells to sustain their trafficking and functions within hypoxic microenvironments
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • PIK3CA/AKT1/MTOR signaling pathway, which was overactivated in aldosterone-producing adenomas (APAs), idiopathic hyperaldosteronism (IHA)compared with normal zona glomerulosa, may mediate aldosterone hypersecretion and participate in the development of primary aldosteronism (PA)
  • central role of PI3K/AKT signaling in vascular, limb and brain development
  • a component
  • heterodimerizing with p85 subunit
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • activating AKTs in the antiapoptotic PIK3 pathway
  • mediating angiogenesis and expression of VGEF in endothelial cells
  • regulates CACNA1C in cardiac myocytes
  • interacts with melusin (ITGB1BP2), and is critical for Z-disc alignment
  • key role of class I PIK3CA in IL2RA endocytosis that creates a link with IL2 signalling
  • RAB39A interacts with PIK3CA and the AAs from 34(th) to 41(st) in RAB39A were indispensable for this interaction
  • FAM3A plays crucial roles in the regulation of glucose and lipid metabolism in the liver, where it activates the PIK3CA-AKT1 signaling pathway by way of a Ca(2+) /CALM1-dependent mechanism
  • CREG1 is a novel factor in regulating endothelial differentiation and vasculogenesis via VEGFA/PIK3CA/AKT1 pathway
  • functional RAS interaction with PIK3CA in host tissue is required for the establishment of a growth-permissive environment for the tumor, particularly for tumor-induced angiogenesis
  • cell & other
    REGULATION
    activated by growth factors,through binding p85 adaptor proteins (PIK3R1,PIK3R2,PIK3R3)
    induced by the oncogenic transcription factor Y-box binding protein-1 (YBX1)
    Other antagonized by PTEN,
    ASSOCIATED DISORDERS
    corresponding disease(s) CLOVES , MCAP , CWS5
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in head and necks squamous cell carcinomas
    tumoral       gain of function
    in colorectal cancer and glioblastoma
    tumoral somatic mutation      
    in anaplastic oligodendrogliomas, in anaplastic astrocytomas, glioblastoma multiforme, and medulloblastomas
    tumoral somatic mutation      
    in breast carcinomas and hepatocellular carcinomas, modulate PI3K signalling to influence tumour behaviour and occur in up to 40p100 of breast cancers
    tumoral somatic mutation      
    in colorectal and gastric carcinomas
    tumoral   amplification    
    in thyroid carcinoma, relatively common and may be a novel mechanism in activating the PI3K/Akt pathway in some thyroid tumors
    tumoral somatic mutation      
    in epidermal nevi (EN) in seborrheic keratoses (SK)in association to mutations in FGFR3
    tumoral somatic mutation      
    are likely to occur late in the development of oral squamous cell carcinoma, and play a crucial role through the PI3K-AKT signaling pathway in cancer progression
    tumoral       gain of function
    in diffuse large B cell lymphoma
    constitutional somatic mutation      
    somatic mosaicism for postzygotic activating mutations in the PIK3CA gene
    constitutional somatic mutation     gain of function
    in Cowden and Cowden-like syndrome
    constitutional somatic mutation     gain of function
    in isolated congenital macrodactyly is caused by somatic activation of the PI3K/AKT cell-signaling pathway and is genetically and biochemically related to other overgrowth syndromes
    constitutional       gain of function
    of PIK3CA/AKT1/MTOR axis in individuals with Down syndrome, with and without AD pathology, in comparison with respective controls
    constitutional somatic mutation      
    cause 54p100 of venous malformation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerbrain 
    therapeutic target in anaplastic oligodendrogliomas, in anaplastic astrocytomas, glioblastoma multiforme, and medulloblastomas
    osteoarticularbone 
    therapeutic agents that target this enzyme have the potential to significantly affect bone homeostasis
    cancerthyroid 
    targeting in the treatment of anaplastic thyroid carcinomas
    tumorvascular 
    inhibitors of PIK3Ca might have therapeutic applications for individuals with CLOVES syndrome or other overgrowth anomalies that are also the result of somatic activating mutations in PIK3CA
    cancer  
    targeting the interaction of RAS with PIK3CA has the potential to impair tumor formation by altering the tumor-host relationship, in addition to previously described tumor cell-autonomous effects
    ANIMAL & CELL MODELS