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    PIK3R5 phosphoinositide-3-kinase regulatory subunit 5 [ Homo sapiens (human) ]

    Gene ID: 23533, updated on 2-Nov-2024

    Summary

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    Official Symbol
    PIK3R5provided by HGNC
    Official Full Name
    phosphoinositide-3-kinase regulatory subunit 5provided by HGNC
    Primary source
    HGNC:HGNC:30035
    See related
    Ensembl:ENSG00000141506 MIM:611317; AllianceGenome:HGNC:30035
    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
    p101; FOAP-2; P101-PI3K; F730038I15Rik
    Summary
    Phosphatidylinositol 3-kinases (PI3Ks) phosphorylate the inositol ring of phosphatidylinositol at the 3-prime position, and play important roles in cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. The PI3Ks are divided into three classes: I, II and III, and only the class I PI3Ks are involved in oncogenesis. This gene encodes the 101 kD regulatory subunit of the class I PI3K gamma complex, which is a dimeric enzyme, consisting of a 110 kD catalytic subunit gamma and a regulatory subunit of either 55, 87 or 101 kD. This protein recruits the catalytic subunit from the cytosol to the plasma membrane through high-affinity interaction with G-beta-gamma proteins. Multiple alternatively spliced transcript variants encoding two distinct isoforms have been found. [provided by RefSeq, Oct 2011]
    Expression
    Biased expression in bone marrow (RPKM 25.8), spleen (RPKM 14.1) and 13 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PIK3R5 in Genome Data Viewer
    Location:
    17p13.1
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (8878916..8965707, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (8786072..8872872, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (8782233..8869024, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes 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 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 phosphoinositide-3-kinase regulatory subunit 6 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 uncharacterized LOC124903922 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:8791248-8792056 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:8792057-8792865 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11713 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11714 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11715 Neighboring gene uncharacterized LOC124903920 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11716 Neighboring gene uncharacterized LOC124903921 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8188 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8189 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8190 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11717 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11718 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:8857999-8858500 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:8858501-8859000 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8191 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8192 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11719 Neighboring gene PIK3R5 divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11720 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11721 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8193 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8194 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:8907139-8907768 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11722 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8195 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:8924225-8924768 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:8936035-8936534 Neighboring gene H3K27ac-H3K4me1 hESC enhancers GRCh37_chr17:8954033-8954690 and GRCh37_chr17:8954691-8955350 Neighboring gene netrin 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:8955351-8956008 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:8956741-8957362 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:8957363-8957982 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:8957983-8958603 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:8990973-8991474 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:8991475-8991974 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:9041579-9042287 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:9054043-9054886 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:9058975-9059476 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:9059477-9059976 Neighboring gene uncharacterized LOC101928266

    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 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. Overexpression of p101 activates PI3Kgamma signaling in T cells and contributes to cell survival. Johnson C, et al. Oncogene, 2007 Oct 25. PMID 17486067
    2. PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors. Quintanilha JCF, et al. Pharmacogenomics J, 2022 Feb. PMID 34775477, Free PMC Article
    3. Phosphatidylinositol 3-kinase: the oncoprotein. Vogt PK, et al. Curr Top Microbiol Immunol, 2010. PMID 20582532, Free PMC Article
    4. A missense mutation in PIK3R5 gene in a family with ataxia and oculomotor apraxia. Al Tassan N, et al. Hum Mutat, 2012 Feb. PMID 22065524
    5. Targetable leukaemia dependency on noncanonical PI3Kγ signalling. Luo Q, et al. Nature, 2024 Jun. PMID 38720074

    See all (32) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Targetable leukaemia dependency on noncanonical PI3Kgamma signalling.
      Title: Targetable leukaemia dependency on noncanonical PI3Kγ signalling.
    2. PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors.
      Title: PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors.
    3. HCP5, as the sponge of miR-1291, facilitates AML cell proliferation and restrains apoptosis via increasing PIK3R5 expression.
      Title: HCP5, as the sponge of miR-1291, facilitates AML cell proliferation and restrains apoptosis via increasing PIK3R5 expression.
    4. G protein betagamma translocation to the Golgi apparatus activates MAPK via p110gamma-p101 heterodimers.
      Title: G protein βγ translocation to the Golgi apparatus activates MAPK via p110γ-p101 heterodimers.
    5. data argue for differential regulatory functions of the non-catalytic subunits and a specific Gbetagamma-dependent regulation of p101 in PI3Kgamma activation.
      Title: Different inhibition of Gβγ-stimulated class IB phosphoinositide 3-kinase (PI3K) variants by a monoclonal antibody. Specific function of p101 as a Gβγ-dependent regulator of PI3Kγ enzymatic activity.
    6. PIK3R5 promoter hypermethylation is associated with oral squamous cell carcinoma.
      Title: Screening of differential promoter hypermethylated genes in primary oral squamous cell carcinoma.
    7. 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.
    8. Our characterization of the PIK3R5 protein and findings suggest that it may play a role in the development of the cerebellum and vermis.
      Title: A missense mutation in PIK3R5 gene in a family with ataxia and oculomotor apraxia.
    9. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    10. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Polymorphisms in innate immunity genes and patients response to dendritic cell-based HIV immuno-treatment.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    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

    Associated conditions

    Description Tests
    Ataxia with oculomotor apraxia type 3
    MedGen: C3554690 OMIM: 615217 GeneReviews: Not available
    		Compare labs

    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

    • FLJ26116

    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 G-protein beta/gamma-subunit complex binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    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 immune response NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in phosphatidylinositol metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of MAP kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in centriolar satellite IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in nucleus IEA
    Inferred from Electronic Annotation
    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 5
    Names
    PI3-kinase p101 subunit
    phosphatidylinositol 4,5-bisphosphate 3-kinase regulatory subunit
    protein FOAP-2
    ptdIns-3-kinase p101

    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_030374.1 RefSeqGene

      Range
      5006..91797
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001142633.3 → NP_001136105.1  phosphoinositide 3-kinase regulatory subunit 5 isoform 1

      See identical proteins and their annotated locations for NP_001136105.1

      Status: REVIEWED

      Source sequence(s)
      AB028925, AK309074, AY725854, BC028212
      Consensus CDS
      CCDS11147.1
      UniProtKB/Swiss-Prot
      B0LPH4, D3DTS3, Q5G936, Q5G938, Q5G939, Q8IZ23, Q8WYR1, Q9Y2Y2
      UniProtKB/TrEMBL
      L7RT34
      Related
      ENSP00000392812.1, ENST00000447110.6
      Conserved Domains (1) summary
      pfam10486
      Location:6 → 880
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    2. NM_001251851.2 → NP_001238780.1  phosphoinositide 3-kinase regulatory subunit 5 isoform 2

      See identical proteins and their annotated locations for NP_001238780.1

      Status: REVIEWED

      Source sequence(s)
      AF128881, AK309074, AY725851, BC028212
      Consensus CDS
      CCDS73986.1
      UniProtKB/Swiss-Prot
      Q8WYR1
      Conserved Domains (1) summary
      pfam10486
      Location:1 → 494
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    3. NM_001251852.2 → NP_001238781.1  phosphoinositide 3-kinase regulatory subunit 5 isoform 2

      See identical proteins and their annotated locations for NP_001238781.1

      Status: REVIEWED

      Source sequence(s)
      AF128881, AK309074, BC028212
      Consensus CDS
      CCDS73986.1
      UniProtKB/Swiss-Prot
      Q8WYR1
      Related
      ENSP00000484211.1, ENST00000616147.4
      Conserved Domains (1) summary
      pfam10486
      Location:1 → 494
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    4. NM_001251853.2 → NP_001238782.1  phosphoinositide 3-kinase regulatory subunit 5 isoform 2

      See identical proteins and their annotated locations for NP_001238782.1

      Status: REVIEWED

      Source sequence(s)
      AB028925, AF128881, AK309074, AY725852, BC028212
      Consensus CDS
      CCDS73986.1
      UniProtKB/Swiss-Prot
      Q8WYR1
      Related
      ENSP00000477795.1, ENST00000611902.4
      Conserved Domains (1) summary
      pfam10486
      Location:1 → 494
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    5. NM_001251855.2 → NP_001238784.1  phosphoinositide 3-kinase regulatory subunit 5 isoform 2

      See identical proteins and their annotated locations for NP_001238784.1

      Status: REVIEWED

      Source sequence(s)
      AF128881, AK309074, BC028212
      Consensus CDS
      CCDS73986.1
      UniProtKB/Swiss-Prot
      Q8WYR1
      Related
      ENSP00000485280.1, ENST00000623421.3
      Conserved Domains (1) summary
      pfam10486
      Location:1 → 494
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    6. NM_001388396.1 → NP_001375325.1  phosphoinositide 3-kinase regulatory subunit 5 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC002091, AC003695
      Consensus CDS
      CCDS92257.1
      UniProtKB/TrEMBL
      J3KSW1
      Related
      ENSP00000462680.1, ENST00000584803.1
      Conserved Domains (1) summary
      pfam10486
      Location:6 → 879
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    7. NM_001388397.1 → NP_001375326.1  phosphoinositide 3-kinase regulatory subunit 5 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC002091, AC003695
      Consensus CDS
      CCDS73986.1
      Conserved Domains (1) summary
      pfam10486
      Location:1 → 494
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    8. NM_001388398.1 → NP_001375327.1  phosphoinositide 3-kinase regulatory subunit 5 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC002091, AC003695
      Consensus CDS
      CCDS73986.1
      Conserved Domains (1) summary
      pfam10486
      Location:1 → 494
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    9. NM_001388399.1 → NP_001375328.1  phosphoinositide 3-kinase regulatory subunit 5 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC002091, AC003695
      Consensus CDS
      CCDS73986.1
      Conserved Domains (1) summary
      pfam10486
      Location:1 → 494
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    10. NM_001388400.1 → NP_001375329.1  phosphoinositide 3-kinase regulatory subunit 5 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC002091, AC003695
      Conserved Domains (1) summary
      pfam10486
      Location:1 → 493
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    11. NM_014308.4 → NP_055123.2  phosphoinositide 3-kinase regulatory subunit 5 isoform 1

      See identical proteins and their annotated locations for NP_055123.2

      Status: REVIEWED

      Source sequence(s)
      AF128881, BC028212
      Consensus CDS
      CCDS11147.1
      UniProtKB/Swiss-Prot
      B0LPH4, D3DTS3, Q5G936, Q5G938, Q5G939, Q8IZ23, Q8WYR1, Q9Y2Y2
      UniProtKB/TrEMBL
      L7RT34
      Related
      ENSP00000462433.1, ENST00000581552.5
      Conserved Domains (1) summary
      pfam10486
      Location:6 → 880
      PI3K_1B_p101; Phosphoinositide 3-kinase gamma adapter protein p101 subunit

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    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
      8878916..8965707 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047435709.1 → XP_047291665.1  phosphoinositide 3-kinase regulatory subunit 5 isoform X1

      UniProtKB/Swiss-Prot
      B0LPH4, D3DTS3, Q5G936, Q5G938, Q5G939, Q8IZ23, Q8WYR1, Q9Y2Y2
      UniProtKB/TrEMBL
      L7RT34

    2. XM_047435711.1 → XP_047291667.1  phosphoinositide 3-kinase regulatory subunit 5 isoform X3

    3. XM_047435710.1 → XP_047291666.1  phosphoinositide 3-kinase regulatory subunit 5 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      8786072..8872872 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054315631.1 → XP_054171606.1  phosphoinositide 3-kinase regulatory subunit 5 isoform X1

      UniProtKB/Swiss-Prot
      B0LPH4, D3DTS3, Q5G936, Q5G938, Q5G939, Q8IZ23, Q8WYR1, Q9Y2Y2
      UniProtKB/TrEMBL
      L7RT34

    2. XM_054315633.1 → XP_054171608.1  phosphoinositide 3-kinase regulatory subunit 5 isoform X3

    3. XM_054315632.1 → XP_054171607.1  phosphoinositide 3-kinase regulatory subunit 5 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8WYR1.1 GenPept UniProtKB/Swiss-Prot:Q8WYR1

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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