Phosphoinositide 3-kinase gamma is a lipid kinase that produces the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. The kinase is composed of a catalytic subunit and one of several regulatory subunits, and is chiefly activated by G protein-coupled receptors. This gene encodes a regulatory subunit, and is distantly related to the phosphoinositide-3-kinase, regul... See more...

Aliases for PIK3R6 Gene

Aliases for PIK3R6 Gene

  • Phosphoinositide-3-Kinase Regulatory Subunit 6 2 3 5
  • P87PIKAP 2 3 4
  • Phosphoinositide 3-Kinase Regulatory Subunit 6 3 4
  • P84 PI3K Adapter Protein 3 4
  • P84 PIKAP 3 4
  • C17orf38 3 4
  • HsT41028 2 3
  • P87 Phosphoinositide 3-Kinase Gamma (PI3Kg) Adapter Protein 3
  • Phosphoinositide 3-Kinase Gamma Adapter Protein Of 87 KDa 4
  • Phosphoinositide-3-Kinase, Regulatory Subunit 6 2
  • Chromosome 17 Open Reading Frame 38 2
  • PI3Kgamma Adapter Protein Of 87 KDa 3
  • P87 PI3K Adapter Protein 4
  • P87(PIKAP) 3
  • FLJ34500 2
  • PIK3R6 5

External Ids for PIK3R6 Gene

Previous HGNC Symbols for PIK3R6 Gene

  • C17orf38

Previous GeneCards Identifiers for PIK3R6 Gene

  • GC17M008647
  • GC17M008706

Summaries for PIK3R6 Gene

Entrez Gene Summary for PIK3R6 Gene

  • Phosphoinositide 3-kinase gamma is a lipid kinase that produces the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. The kinase is composed of a catalytic subunit and one of several regulatory subunits, and is chiefly activated by G protein-coupled receptors. This gene encodes a regulatory subunit, and is distantly related to the phosphoinositide-3-kinase, regulatory subunit 5 gene which is located adjacent to this gene on chromosome 7. The orthologous protein in the mouse binds to both the catalytic subunit and to G(beta/gamma), and mediates activation of the kinase subunit downstream of G protein-coupled receptors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

GeneCards Summary for PIK3R6 Gene

PIK3R6 (Phosphoinositide-3-Kinase Regulatory Subunit 6) is a Protein Coding gene. Among its related pathways are Signaling by GPCR and Apelin signaling pathway. Gene Ontology (GO) annotations related to this gene include 1-phosphatidylinositol-3-kinase regulator activity and phosphatidylinositol-4,5-bisphosphate 3-kinase activity. An important paralog of this gene is PIK3R5.

UniProtKB/Swiss-Prot Summary for PIK3R6 Gene

  • Regulatory subunit of the PI3K gamma complex. Acts as an adapter to drive activation of PIK3CG by beta-gamma G protein dimers. The PIK3CG:PIK3R6 heterodimer is much less sensitive to beta-gamma G protein dimers than PIK3CG:PIK3R5 and its membrane recruitment and beta-gamma G protein dimer-dependent activation requires HRAS bound to PIK3CG. Recruits of the PI3K gamma complex to a PDE3B:RAPGEF3 signaling complex involved in angiogenesis; signaling seems to involve RRAS.

Additional gene information for PIK3R6 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PIK3R6 Gene

Genomics for PIK3R6 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PIK3R6 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH17J008865 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE dbSUPER 620.2 +3.1 3076 2.7 POLR2A BACH1 ZNF143 SMAD5 RUNX3 CBFB ARNT NBN HDGF CHD1 PIK3R6 LOC107985071 lnc-PIK3R6-1 ENSG00000265749 RPL26 PFAS CNTROB SPDYE4 hsa-miR-5095-210 MFSD6L
GH17J008868 Enhancer 0.8 ENCODE dbSUPER 600.7 +1.2 1204 0.2 IKZF2 RCOR1 PKNOX1 DPF2 RUNX3 BCL11A ARNT IKZF1 NR2F1 JUNB LOC107985071 PIK3R6 lnc-PIK3R6-1 MFSD6L
GH17J008856 Enhancer 1.4 FANTOM5 ENCODE CraniofacialAtlas dbSUPER 24.4 +10.6 10590 5 SP1 POLR2A BACH1 STAT3 ZNF143 RELA ZIC2 TCF12 IKZF2 TRIM22 PIK3R6 PFAS PIK3R5 RPL26 CTC1 SPDYE4 CNTROB NDEL1 lnc-PIK3R6-1 hsa-miR-5095-210
GH17J008412 Promoter/Enhancer 1.7 EPDnew FANTOM5 Ensembl ENCODE 9.1 +456.6 456621 2.4 PRDM10 ZNF629 JUND DPF2 HDAC1 SOX6 CEBPA SCRT2 CEBPB ZNF639 NDEL1 lnc-ODF4-4 WRAP53 RPL26 KRBA2 ZBTB4 SLC25A35 RANGRF PFAS PIK3R6
GH17J008872 Enhancer 0.7 Ensembl dbSUPER 20.2 -4.0 -3997 4 POLR2A ZSCAN4 MNT FOXA2 FOXP1 REST STAT5A YY1 SOX5 TAF1 PIK3R6 LOC107985063 PIK3R5
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PIK3R6 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PIK3R6

Top Transcription factor binding sites by QIAGEN in the PIK3R6 gene promoter:
  • AML1a
  • AP-1
  • c-Fos
  • c-Jun
  • MyoD
  • Pax-3
  • Pax-4a
  • POU2F1
  • POU2F1a
  • Sox5

Genomic Locations for PIK3R6 Gene

Genomic Locations for PIK3R6 Gene
chr17:8,802,722-8,870,003
(GRCh38/hg38)
Size:
67,282 bases
Orientation:
Minus strand
chr17:8,706,041-8,770,994
(GRCh37/hg19)
Size:
64,954 bases
Orientation:
Minus strand

Genomic View for PIK3R6 Gene

Genes around PIK3R6 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PIK3R6 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PIK3R6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PIK3R6 Gene

Proteins for PIK3R6 Gene

  • Protein details for PIK3R6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q5UE93-PI3R6_HUMAN
    Recommended name:
    Phosphoinositide 3-kinase regulatory subunit 6
    Protein Accession:
    Q5UE93
    Secondary Accessions:
    • Q658R3

    Protein attributes for PIK3R6 Gene

    Size:
    754 amino acids
    Molecular mass:
    84258 Da
    Quaternary structure:
    • Heterodimer of a catalytic subunit (PIK3CG) and a regulatory (PIK3R6) subunit. The binding of PIK3R6 to PIK3CG may exclude the binding of PIK3R5 to PIK3CG. Interacts with beta-gamma G protein dimers. Interacts with PDE3B; the interaction allows recruitment of the PI3K gamma complex to a PDE3B:RAPGEF3 complex.

neXtProt entry for PIK3R6 Gene

Post-translational modifications for PIK3R6 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for PIK3R6 Gene

Domains & Families for PIK3R6 Gene

Gene Families for PIK3R6 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for PIK3R6 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for PIK3R6 Gene

GenScript: Design optimal peptide antigens:
  • PIK3R6 protein (A4FVB8_HUMAN)
  • p87 PI3K adapter protein (PI3R6_HUMAN)
genes like me logo Genes that share domains with PIK3R6: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for PIK3R6 Gene

Function for PIK3R6 Gene

Molecular function for PIK3R6 Gene

UniProtKB/Swiss-Prot Function:
Regulatory subunit of the PI3K gamma complex. Acts as an adapter to drive activation of PIK3CG by beta-gamma G protein dimers. The PIK3CG:PIK3R6 heterodimer is much less sensitive to beta-gamma G protein dimers than PIK3CG:PIK3R5 and its membrane recruitment and beta-gamma G protein dimer-dependent activation requires HRAS bound to PIK3CG. Recruits of the PI3K gamma complex to a PDE3B:RAPGEF3 signaling complex involved in angiogenesis; signaling seems to involve RRAS.

Phenotypes From GWAS Catalog for PIK3R6 Gene

Gene Ontology (GO) - Molecular Function for PIK3R6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 21393242
GO:0046934 contributes_to phosphatidylinositol-4,5-bisphosphate 3-kinase activity IEA,ISS --
GO:0046935 1-phosphatidylinositol-3-kinase regulator activity IEA,ISS --
genes like me logo Genes that share ontologies with PIK3R6: view
genes like me logo Genes that share phenotypes with PIK3R6: view

Animal Models for PIK3R6 Gene

MGI Knock Outs for PIK3R6:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PIK3R6

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for PIK3R6 Gene

Localization for PIK3R6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PIK3R6 Gene

Cytoplasm. Cell membrane. Peripheral membrane protein. Note=Translocated to the plasma membrane in a Ras-dependent manner. {ECO:0000250 UniProtKB:Q3U6Q4}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PIK3R6 gene
Compartment Confidence
plasma membrane 4
cytosol 4
extracellular 1
cytoskeleton 1
nucleus 1
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Golgi apparatus (2)
  • Nucleoplasm (2)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PIK3R6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IEA --
GO:0005942 phosphatidylinositol 3-kinase complex IBA 21873635
GO:0005944 phosphatidylinositol 3-kinase complex, class IB IEA,ISS --
genes like me logo Genes that share ontologies with PIK3R6: view

Pathways & Interactions for PIK3R6 Gene

genes like me logo Genes that share pathways with PIK3R6: view

Gene Ontology (GO) - Biological Process for PIK3R6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis IEA --
GO:0006661 phosphatidylinositol biosynthetic process TAS --
GO:0007186 G protein-coupled receptor signaling pathway IEA,ISS --
GO:0030168 platelet activation TAS --
GO:0042269 regulation of natural killer cell mediated cytotoxicity IDA 11062502
genes like me logo Genes that share ontologies with PIK3R6: view

No data available for SIGNOR curated interactions for PIK3R6 Gene

Drugs & Compounds for PIK3R6 Gene

(21) Drugs for PIK3R6 Gene - From: DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
SF1126 Investigational Pharma inhibitor Kinase Inhibitors 0
BAY80-6946 Pharma Inhibition, Biomarker, inhibitor PI3K Inhibitors, Kinase Inhibitors 0
BEZ235 Pharma Inhibition, inhibitor PI3K/mTOR inhibitor, Kinase Inhibitors, Phosphatidylinositol-3- kinase (PI-3K) inhibitors, PI3K/mTOR Inhibitors 0
BGJ398 Pharma Inhibition, inhibitor FGFR inhibitor ,potent and selective, Kinase Inhibitors, Fibroblast growth factor receptor (FGFR)inhibitors 0
BKM120 Pharma Inhibition, inhibitor Inhibitor of pan-Class I PI3K, pan-PI3K inhibitor, Kinase Inhibitors, Phosphatidylinositol-3- kinase (PI-3K) inhibitors 0
genes like me logo Genes that share compounds with PIK3R6: view

Transcripts for PIK3R6 Gene

mRNA/cDNA for PIK3R6 Gene

2 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PIK3R6

Alternative Splicing Database (ASD) splice patterns (SP) for PIK3R6 Gene

No ASD Table

Relevant External Links for PIK3R6 Gene

GeneLoc Exon Structure for
PIK3R6

Expression for PIK3R6 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PIK3R6 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for PIK3R6 Gene

This gene is overexpressed in Liver, secretome (41.0), Peripheral blood mononuclear cells (21.6), and Platelet (6.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for PIK3R6 Gene



Protein tissue co-expression partners for PIK3R6 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PIK3R6

SOURCE GeneReport for Unigene cluster for PIK3R6 Gene:

Hs.255809

Evidence on tissue expression from TISSUES for PIK3R6 Gene

  • Stomach(4)
genes like me logo Genes that share expression patterns with PIK3R6: view

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for PIK3R6 Gene

Orthologs for PIK3R6 Gene

This gene was present in the common ancestor of chordates.

Orthologs for PIK3R6 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PIK3R6 30
  • 98.94 (n)
Dog
(Canis familiaris)
Mammalia PIK3R6 30
  • 86.39 (n)
Cow
(Bos Taurus)
Mammalia PIK3R6 30
  • 85.93 (n)
Mouse
(Mus musculus)
Mammalia Pik3r6 30 17
  • 82.64 (n)
Rat
(Rattus norvegicus)
Mammalia Pik3r6 30
  • 82.06 (n)
Chicken
(Gallus gallus)
Aves PIK3R6 30
  • 64.48 (n)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia pik3r6 30
  • 58.71 (n)
Zebrafish
(Danio rerio)
Actinopterygii LOC100007492 30
  • 51.47 (n)
Species where no ortholog for PIK3R6 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for PIK3R6 Gene

ENSEMBL:
Gene Tree for PIK3R6 (if available)
TreeFam:
Gene Tree for PIK3R6 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PIK3R6: view image

Paralogs for PIK3R6 Gene

Paralogs for PIK3R6 Gene

genes like me logo Genes that share paralogs with PIK3R6: view

Variants for PIK3R6 Gene

Additional dbSNP identifiers (rs#s) for PIK3R6 Gene

Structural Variations from Database of Genomic Variants (DGV) for PIK3R6 Gene

Variant ID Type Subtype PubMed ID
dgv534e199 CNV deletion 23128226
esv2530577 CNV insertion 19546169
esv2656928 CNV deletion 23128226
esv2661814 CNV deletion 23128226
esv2668684 CNV deletion 23128226
esv2677297 CNV deletion 23128226
esv2715619 CNV deletion 23290073
esv2715620 CNV deletion 23290073
esv3440912 CNV duplication 20981092
esv3554109 CNV deletion 23714750
esv3639892 CNV loss 21293372
esv3639893 CNV loss 21293372
esv3639894 CNV loss 21293372
esv994892 CNV deletion 20482838
nsv1070387 CNV deletion 25765185
nsv1071335 CNV deletion 25765185
nsv1071369 CNV deletion 25765185
nsv1071370 CNV deletion 25765185
nsv1116187 CNV deletion 24896259
nsv1134596 CNV deletion 24896259
nsv1138497 CNV deletion 24896259
nsv1138498 CNV deletion 24896259
nsv1969 CNV deletion 18451855
nsv1970 CNV deletion 18451855
nsv480842 CNV novel sequence insertion 20440878
nsv518675 CNV gain 19592680
nsv521208 CNV loss 19592680
nsv953828 CNV deletion 24416366

Variation tolerance for PIK3R6 Gene

Gene Damage Index Score: 4.02; 60.37% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PIK3R6 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PIK3R6

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PIK3R6 Gene

Disorders for PIK3R6 Gene

No disorders were found for PIK3R6 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for PIK3R6 Gene

Publications for PIK3R6 Gene

  1. Characterization of p87PIKAP, a novel regulatory subunit of phosphoinositide 3-kinase gamma that is highly expressed in heart and interacts with PDE3B. (PMID: 16476736) Voigt P … Schaefer M (The Journal of biological chemistry 2006) 2 3 4
  2. A phosphodiesterase 3B-based signaling complex integrates exchange protein activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human arterial endothelial cells. (PMID: 21393242) Wilson LS … Maurice DH (The Journal of biological chemistry 2011) 3 4
  3. p84 forms a negative regulatory complex with p110γ to control PI3Kγ signalling during cell migration. (PMID: 25753393) Turvey ME … McColl SR (Immunology and cell biology 2015) 3
  4. p87 and p101 subunits are distinct regulators determining class IB phosphoinositide 3-kinase (PI3K) specificity. (PMID: 24014027) Shymanets A … Nürnberg B (The Journal of biological chemistry 2013) 3
  5. GPCR activation of Ras and PI3Kc in neutrophils depends on PLCb2/b3 and the RasGEF RasGRP4. (PMID: 22728827) Suire S … Stephens L (The EMBO journal 2012) 3

Products for PIK3R6 Gene

Sources for PIK3R6 Gene