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FLASH GENE
Symbol PIK3R1 contributors: mct - updated : 06-09-2017
HGNC name phosphoinositide-3-kinase, regulatory subunit, polypeptide 1 (p85 alpha)
HGNC id 8979
Corresponding disease
IMD36 Immunodeficiency 36
SHORT SHORT syndrome
Location 5q13.1      Physical location : 67.522.461 - 67.597.647
Synonym name phosphatidylinositol 3-kinase-associated p-85 alpha
Synonym symbol(s) PI3KA, GRB1, p85-ALPHA, AGM7, IMD36, p85
EC.number 2.7.1.-
DNA
TYPE functioning gene
STRUCTURE 86.08 kb     16 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status provisional
Physical map
LOC202227 5q13.1 similar to peptidylprolyl isomerase A (cyclophilin A) LOC375449 5q13.1 similar to microtubule associated testis specific serine/threonine protein kinase KIAA0303 5q11.2-q12 similar to microtubule associated testis specific serine/threonine protein kinase LY64 5q12 lymphocyte antigen 64 homolog, radioprotective 105kDa (mouse) LOC206227 5q13.1 similar to B-cell lymphoma 9 protein (Bcl-9) (Legless homolog) LOC359819 5q12.3 mitochondrial ribosomal protein L39 pseudogene EEF1B3 5q12-q14 eukaryotic translation elongation factor 1 beta 3 PIK3R1 5q12-q13 phosphoinositide-3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) SLC30A5 5q12.1 solute carrier family 30 (zinc transporter), member 5 CCNB1 5q11-q12 cyclin B1 CENPH 5p15.2 centromere protein H MRPS36 5q13.3 mitochondrial ribosomal protein S36 CDK7 2p15-pcen cyclin-dependent kinase 7 (MO15 homolog, Xenopus laevis, cdk-activating kinase) KENAE 5q13.1 Kenae LOC285653 5q13.1 similar to chromosome 7 open reading frame 17 protein; 16.7kD protein TAF9 5q12 TAF9 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 32kDa RAD17 5q12-q13.1 RAD17 homolog (S. pombe) FLJ30532 5q13.1 hypothetical protein FLJ30532 OCLN 5q13.1 occludin GTF2H2 5q13.1 general transcription factor IIH, polypeptide 2, 44kDa BIRC1 5q13.1 baculoviral IAP repeat-containing 1 SMN1 5q13.1 survival of motor neuron 1, telomeric LOC391791 5 similar to cadherin 12, type 2 preproprotein; Br-cadherin; cadherin-12; N-cadherin 2; brain-cadherin; neuronal cadherin 2; cadherin, neural type, 2 SMA3 5q13 SMA3
RNA
TRANSCRIPTS type messenger
text with three alternatively spliced isoforms : p85 alpha, p55 alpha and p50 alpha (Inukai)
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
16 - 6991 85 724 - 2005 16166093
  • p85 alpha
  • 10 - 5691 55 454 - 2005 16166093
  • p55 alpha
  • 10 - 5823 50 424 - 2005 16166093
  • p50 alpha
  • 9 - 5554 - 361 - 2005 16166093
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Lymphoid/Immunespleen   highly
    Nervousnerve   highly
    Reproductivefemale systemuterus  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
     adipocyte
    Lymphoid/ImmuneB cell
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal SH3,
  • a Rho-GAP domain
  • two SH2 domains (nSH2 and cSH2)
  • a region of homology to the C terminal region of BCR
  • a compact beta-barrel fold very similar to that of PIK3R2 but the ligand-binding specificity differs slightly between the SH3 domains of PIK3R1 and PIK3R2, despite their high structural similarity
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY enzyme , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • acting as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane
  • required for insulin-stimulated increase in glucose uptake and glycogen synthesis
  • PIK3R1, PIK3R2 modulate PI 3-kinase-dependent signaling by multiple mechanisms and transmit signals independent of PI 3-kinase activation
  • is likely a determining factor in ICOS-mediated PI3K activity in T cells
  • PIK3R1 and PIK3CB are essential for androgen-stimulated androgen receptor transactivation, and their aberrant expression or activation might play an important role in prostate cancer progression
  • critical regulators of various cellular process including cell survival, growth, proliferation, and motility
  • PIK3R1 regulatory isoform has partially overlapping functions with PIK3R1 in B cells as well as a unique role in opposing BCR responses
  • plays an important role in regulating many cellular processes including cell growth, survival, proliferation, and motility
  • its expression plays a critical role in mediating adipose tissue (AT) insulin sensitivity, suggesting that reduced PIK3R1 activity is a key step in the initiation and propagation of the inflammatory response in obese AT
  • is a highly dynamic molecule whose conformational flexibility allows it to transiently associate with multiple binding proteins
  • novel role of PIK3R1 that was independent of the regulatory function of phosphoinositide 3-kinase in mediating the metabolic action of glucocorticoids
  • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    adipocyte differentiation
    a component
  • interacting with inositol polyphosphatase 4-phosphatase and inositol polyphosphatase 5-phosphatase forming complex with SHIP (INPP5D) and SHP2 (PTPN11)
  • heterodimer of a p110 catalytic subunit and a p85 regulatory subunit
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain)
  • interacting with tyrosine kinase (signal transduction)
  • interacting with IRS1 and playing a potential role in glucose homeostasis
  • COASY is involved in signaling events in the cell and forms a functional complex with PIK3R1
  • directly interacting with the estrogen receptor alpha
  • CMIP interacts with the PIK3R1, PIK3R2 and inactivates LCK, which results in Erk1/2 and MAPK14 activation
  • regulatory subunits PIK3R1, PIK3R2, interact with XBP1 and increase its nuclear translocation
  • CBL ubiquitination of PIK3R1 is essential for EPO-induced EPOR endocytosis
  • is a glucocorticoid receptor target gene
  • cell & other
    REGULATION
    Phosphorylated by PRKD1 (mediates phosphorylation of S652 in the C-terminal SH2 domain)
    ASSOCIATED DISORDERS
    corresponding disease(s) SHORT , IMD36
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    may be one of the earliest molecular alterations in the mechanism of the insulin resistance associated with overfeeding
    tumoral germinal mutation     loss of function
    inactivating mutations in TSC2 and PIK3R1 in urothelial carcinoma
    tumoral somatic mutation      
    in endometrioid endometrial cancers (EEC)
    tumoral     --low  
    in prostate, lung, ovarian, bladder, and liver cancers, consistent with the possibility that PIK3R1 has tumor suppressor properties
    tumoral     --low  
    significantly decreased in primary in renal cell carcinoma (RCC), which promotes propagation, migration, EMT and stem-like phenotype in renal cancer cells, and may contribute to progression and metastasis of RCC
    tumoral somatic mutation      
    in glioblastoma (GBM)
    Susceptibility to diabetes with insulin resistance in healthy women of normal weight
    Variant & Polymorphism SNP Met326Ile variant modifying insulin action
    Candidate gene
    Marker
    Therapy target potential role for reducing p85alpha as a therapeutic strategy for enhancing insulin sensitivity in skeletal muscle
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    therapeutic target for breast cancer therapy
    diabete  
    modulation of PIK3R1 can protect pancreatic beta-cells from ER stress, pointing to a potentially therapeutic target in diabetic states
    ANIMAL & CELL MODELS