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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
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
  • signaling pathway that controls angiogenesis immediately downstream of PIK3CA through ARAP3 to the RHO and ARF family of small GTPases
  • 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
  • PIK3CA signalling prevents NUAK1-dependent phosphorylation of PPP1R12A protein, thereby allowing myosin light chain phosphatase (MLCP) activity and ultimately downregulating actomyosin contractility
  • 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