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    PIK3R6 phosphoinositide-3-kinase regulatory subunit 6 [ Homo sapiens (human) ]

    Gene ID: 146850, updated on 3-Apr-2024

    Summary

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    Official Symbol
    PIK3R6provided by HGNC
    Official Full Name
    phosphoinositide-3-kinase regulatory subunit 6provided by HGNC
    Primary source
    HGNC:HGNC:27101
    See related
    Ensembl:ENSG00000276231 MIM:611462; AllianceGenome:HGNC:27101
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    C17orf38; HsT41028; p87PIKAP; p84 PIKAP; p87(PIKAP)
    Summary
    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]
    Expression
    Broad expression in spleen (RPKM 2.7), appendix (RPKM 1.8) and 19 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    17p13.1
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (8802722..8867677, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (8708926..8774833, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (8706040..8770994, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371530 Neighboring gene uncharacterized LOC124903918 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8187 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11702 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11703 Neighboring gene MPRA-validated peak2720 silencer Neighboring gene major facilitator superfamily domain containing 6 like Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:8730902-8731702 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:8731703-8732503 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11705 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:8740143-8740949 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11706 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11707 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11708 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11709 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11710 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11711 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11712 Neighboring gene uncharacterized LOC107985071 Neighboring gene uncharacterized LOC124903919 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:8788211-8788374 Neighboring gene phosphoinositide-3-kinase regulatory subunit 5

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. RBBP6 aggravates the progression of ovarian cancer by targeting PIK3R6. Liu YJ, et al. Eur Rev Med Pharmacol Sci, 2020 Oct. PMID 33155192
    2. p84 forms a negative regulatory complex with p110γ to control PI3Kγ signalling during cell migration. Turvey ME, et al. Immunol Cell Biol, 2015 Sep. PMID 25753393
    3. p87 and p101 subunits are distinct regulators determining class IB phosphoinositide 3-kinase (PI3K) specificity. Shymanets A, et al. J Biol Chem, 2013 Oct 25. PMID 24014027, Free PMC Article
    4. Pivotal role of phosphoinositide-3 kinase in regulation of cytotoxicity in natural killer cells. Jiang K, et al. Nat Immunol, 2000 Nov. PMID 11062502
    5. Function, Regulation and Biological Roles of PI3Kγ Variants. Nürnberg B, et al. Biomolecules, 2019 Aug 30. PMID 31480354, Free PMC Article

    See all (22) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. PIK3R6 Promotes Angiogenesis in Hepatocellular carcinoma by Activating STAT3 Signaling Pathway.
      Title: PIK3R6 Promotes Angiogenesis in Hepatocellular carcinoma by Activating STAT3 Signaling Pathway.
    2. RBBP6 aggravates the progression of ovarian cancer by targeting PIK3R6.
      Title: RBBP6 aggravates the progression of ovarian cancer by targeting PIK3R6.
    3. Our findings suggest that p84 binding to p110gamma may represent a novel negative feedback signal that terminates PI3Kgamma activity.
      Title: p84 forms a negative regulatory complex with p110γ to control PI3Kγ signalling during cell migration.
    4. expression and activities of PI3Kgamma are modified differently by p87 and p101 in vitro and in living cells, arguing for specific regulatory roles of the non-catalytic subunits in the differentiation of PI3Kgamma signaling pathways.
      Title: p87 and p101 subunits are distinct regulators determining class IB phosphoinositide 3-kinase (PI3K) specificity.
    5. knockdown of p84 in MDA-MB-231 cells enhanced Akt phosphorylation and lung colonization
      Title: Differential roles for the p101 and p84 regulatory subunits of PI3Kγ in tumor growth and metastasis.
    6. GPCR activation of Ras and PI3Kc in neutrophils depends on PLCb2/b3 and the RasGEF RasGRP4.
      Title: GPCR activation of Ras and PI3Kc in neutrophils depends on PLCb2/b3 and the RasGEF RasGRP4.
    7. RACK1 regulates directional cell migration by acting on G betagamma at the interface with its effectors PLC beta and PI3K gamma
      Title: RACK1 regulates directional cell migration by acting on G betagamma at the interface with its effectors PLC beta and PI3K gamma.
    8. ablation of PI3Kgamma reduced SDF1alpha-induced integrin activation in human EPCs and in murine Lin(-) BM-derived progenitor cells
      Title: Phosphatidylinositol-3-kinase-gamma is integral to homing functions of progenitor cells.
    9. p87PIKAP is a novel regulatory subunit of phosphoinositide 3-kinase gamma that is highly expressed in heart and interacts with PDE3B [p87PIKAP]
      Title: Characterization of p87PIKAP, a novel regulatory subunit of phosphoinositide 3-kinase gamma that is highly expressed in heart and interacts with PDE3B.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ34500, DKFZp666P158

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 1-phosphatidylinositol-3-kinase regulator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 1-phosphatidylinositol-3-kinase regulator activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    contributes_to 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in G protein-coupled receptor signaling pathway EXP
    Inferred from Experiment
    more info
    		 PubMed 
    involved_in G protein-coupled receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in G protein-coupled receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in angiogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in immune response NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of MAP kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of MAP kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of T cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of angiogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of natural killer cell mediated cytotoxicity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    part_of phosphatidylinositol 3-kinase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of phosphatidylinositol 3-kinase complex, class IA EXP
    Inferred from Experiment
    more info
    		 PubMed 
    part_of phosphatidylinositol 3-kinase complex, class IB ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    phosphoinositide 3-kinase regulatory subunit 6
    Names
    PI3Kgamma adapter protein of 87 kDa
    p84 PI3K adapter protein
    p87 phosphoinositide 3-kinase gamma (PI3Kg) adapter protein

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_033091.1 RefSeqGene

      Range
      5004..69956
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001010855.4 → NP_001010855.1  phosphoinositide 3-kinase regulatory subunit 6 isoform 1

      See identical proteins and their annotated locations for NP_001010855.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AC003695, AC009451, KF573668
      Consensus CDS
      CCDS73985.1
      UniProtKB/Swiss-Prot
      Q5UE93, Q658R3
      Related
      ENSP00000480157.1, ENST00000619866.5
      Conserved Domains (1) summary
      pfam10486
      Location:18 → 751
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    2. NM_001290211.1 → NP_001277140.1  phosphoinositide 3-kinase regulatory subunit 6 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in its 5' UTR and uses a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AK091819, BC110301, DB326284
      UniProtKB/TrEMBL
      A4FVB8
      Conserved Domains (1) summary
      pfam10486
      Location:1 → 615
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    RNA

    1. NR_110865.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses two alternate splice sites at internal exons, lacks an internal exon, and contains an alternate 3' exon, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
      Source sequence(s)
      AC009451, AK091819, DB326284
      Related
      ENST00000613555.4

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      8802722..8867677 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047435450.1 → XP_047291406.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X10

    2. XM_047435452.1 → XP_047291408.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X12

    3. XM_047435444.1 → XP_047291400.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X4

    4. XM_047435448.1 → XP_047291404.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X7

    5. XM_011523678.3 → XP_011521980.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X3

      Conserved Domains (1) summary
      pfam10486
      Location:18 → 540
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    6. XM_047435447.1 → XP_047291403.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X6

    7. XM_011523680.3 → XP_011521982.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X9

      Conserved Domains (1) summary
      pfam10486
      Location:18 → 460
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    8. XM_047435451.1 → XP_047291407.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X11

    9. XM_011523677.3 → XP_011521979.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X2

      Conserved Domains (1) summary
      pfam10486
      Location:18 → 544
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    10. XM_047435446.1 → XP_047291402.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X5

    11. XM_047435443.1 → XP_047291399.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X1

    12. XM_047435454.1 → XP_047291410.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X13

    13. XM_011523683.3 → XP_011521985.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X13

      See identical proteins and their annotated locations for XP_011521985.1

      Conserved Domains (1) summary
      pfam10486
      Location:24 → 465
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    14. XM_047435453.1 → XP_047291409.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X13

    15. XM_047435457.1 → XP_047291413.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X15

    16. XM_011523686.3 → XP_011521988.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X16

      Conserved Domains (1) summary
      pfam10486
      Location:106 → 256
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    17. XM_047435456.1 → XP_047291412.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X14

    18. XM_047435449.1 → XP_047291405.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X8

    19. XM_047435458.1 → XP_047291414.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X17

    RNA

    1. XR_007065269.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      8708926..8774833 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054315186.1 → XP_054171161.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X10

    2. XM_054315188.1 → XP_054171163.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X12

    3. XM_054315180.1 → XP_054171155.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X4

    4. XM_054315183.1 → XP_054171158.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X7

    5. XM_054315179.1 → XP_054171154.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X3

    6. XM_054315182.1 → XP_054171157.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X6

    7. XM_054315185.1 → XP_054171160.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X9

    8. XM_054315187.1 → XP_054171162.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X11

    9. XM_054315178.1 → XP_054171153.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X2

    10. XM_054315181.1 → XP_054171156.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X5

    11. XM_054315177.1 → XP_054171152.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X1

    12. XM_054315189.1 → XP_054171164.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X13

    13. XM_054315193.1 → XP_054171168.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X15

    14. XM_054315190.1 → XP_054171165.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X13

    15. XM_054315191.1 → XP_054171166.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X13

    16. XM_054315194.1 → XP_054171169.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X16

    17. XM_054315192.1 → XP_054171167.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X14

    18. XM_054315184.1 → XP_054171159.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X8

    19. XM_054315195.1 → XP_054171170.1  phosphoinositide 3-kinase regulatory subunit 6 isoform X17

    RNA

    1. XR_008484788.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q5UE93.1 GenPept UniProtKB/Swiss-Prot:Q5UE93

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