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    PIK3C3 phosphatidylinositol 3-kinase catalytic subunit type 3 [ Homo sapiens (human) ]

    Gene ID: 5289, updated on 3-Dec-2024

    Summary

    Official Symbol
    PIK3C3provided by HGNC
    Official Full Name
    phosphatidylinositol 3-kinase catalytic subunit type 3provided by HGNC
    Primary source
    HGNC:HGNC:8974
    See related
    Ensembl:ENSG00000078142 MIM:602609; AllianceGenome:HGNC:8974
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    VPS34; Vps34; hVps34
    Summary
    Enables 1-phosphatidylinositol-3-kinase activity. Involved in several processes, including early endosome to late endosome transport; macroautophagy; and phosphatidylinositol-3-phosphate biosynthetic process. Acts upstream of or within autophagy and protein lipidation. Located in autolysosome; late endosome; and midbody. Part of phosphatidylinositol 3-kinase complex, class III. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Ubiquitous expression in testis (RPKM 7.2), brain (RPKM 7.0) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See PIK3C3 in Genome Data Viewer
    Location:
    18q12.3
    Exon count:
    27
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (41955234..42087830)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (42146975..42279510)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (39535199..39667794)

    Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene chromosome 15 open reading frame 40 pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:39445727-39446283 Neighboring gene uncharacterized LOC105372085 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13247 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13248 Neighboring gene uncharacterized LOC124904350 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13249 Neighboring gene long intergenic non-protein coding RNA 907 Neighboring gene RNA, 5S ribosomal pseudogene 454

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies loci affecting blood copper, selenium and zinc.
    EBI GWAS Catalog
    Genome-wide association study of chronic periodontitis in a general German population.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env CCR5 activation by gp120 triggers the assembly of endogenous Lyn, PI3K, and Pyk2 and is associated with PI3K and Pyk2 translocation from the cytoplasm to the membrane where they colocalized with Lyn PubMed
    env Concomitant activation of Lyn, Pyk2, and class IA PI3K are required for gp120-induced IL-1beta production PubMed
    env Insulin-like growth factor-I (IGF-I) and erythropoietin treatment protect against HIV/gp120-mediated neuronal damage in culture and in vivo, in part, through cooperative activation of phosphatidylinositol 3-kinase/Akt/GSK-3beta signaling PubMed
    env HIV-1 gp120-induced TNF-alpha production by primary human macrophages is mediated by phosphatidylinositol-3 (PI-3) kinase and mitogen-activated protein (MAP) kinase pathways PubMed
    env CD45 modulates HIV-1 gp120-induced apoptosis by regulating Fas ligand induction and activation of the phosphoinositide 3-kinase/Akt pathway PubMed
    env Pre-treatment of endothelial cells with fibroblast growth factor 2 (FGF2) protects cells from HIV-1 gp120 angiotoxicity; this protection is regulated by crosstalk among the ERK, PI3K-AKT and PKC signaling pathways PubMed
    env HIV-1 gp120-induced PI3-kinase activity and calcium mobilization are inhibited by pertussis toxin and blocking antibodies directed against CCR5 and CXCR4, suggesting that this signaling is mediated through these chemokine receptors PubMed
    Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 disrupts the association between phospholipase C gamma-1 and phosphoinositide 3 kinase (PI3-kinase), and this effect is dependent on PI3-kinase activity PubMed
    env PI3-kinase activation induced by HIV-1 gp160 leads to downregulation of LFA-1-mediated T cell adhesion to B cells PubMed
    Nef nef Downregulation of cell surface major histocompatibility complex class I (MHC-I) protein expression by HIV-1 Nef depends on a phosphoinositide 3-kinase (PI3K)-regulated signaling pathway, suggesting an interaction between Nef and PI3K PubMed
    nef In the context of Nef-associated kinase complex (NAKC), hnRNP-K interacts with HIV-1 Nef and recruits LCK, PKCdelta, and PI-3 kinase PubMed
    nef The presence of HIV-1 Nef in Jurkat cells stimulated with a combination of PMA and anti-CD28 upregulates the levels of PI3K production PubMed
    nef The association of phosphatidylinositol (PI) 3-kinase with platelet-derived growth factor (PDGF) activated receptor was downregulated by HIV-1 nef expression PubMed
    Tat tat HIV-1 Tat induces phosphorylation of PI3K, AKT, PTEN, and GSK-3beta activating PI3K and AKT and inactivating PTEN and GSK-3beta in vIL-6 expressing cells PubMed
    tat HIV-1 Tat-induced upregulation of IDO production requires the activity of IFN-gamma signaling pathway such as JAK and PI3K in human monocyte derived-dendritic cells PubMed
    tat Phosphatidylinositol 3-kinase/Akt signaling pathway is involved in HIV-1 Tat-induced NADPH oxidase stimulation and LTR transactivation PubMed
    tat HIV-1 Tat in combination with KSHV kaposin A activates the MEK/ERK, STAT3, and PI3K/Akt signals in NIH3T3 cells PubMed
    tat HIV-1 Tat-mediated cytopathic changes in human brain micro vascular endothelial cells involves its interaction with phosphatidylinositol 3-kinase (PI3K) PubMed
    tat Pro-survival effects of intracellular HIV-1 Tat in a microglial cell line is attributed to activation of the PI-3-kinase (PI3K)/Akt pathway via decreasing expression of PTEN, a negative regulator of the PI-3-K pathway PubMed
    tat HIV-1 Tat activates phosphatidylinositol 3-kinase (PI3K), leading to the activation of Akt/PKB, decreased levels of cAMP and CREB phosphorylation, and the protection of cells from apoptosis PubMed
    tat Phosphatidylinositol 3-kinase inhibits HIV-1 Tat-mediated transactivation of the HIV-1 LTR promoter by affecting the formation of the Tat-associated kinase transactivating complex PubMed
    tat HIV-1 Tat induced release of MCP-1 from human lung microvascular endothelial cells involves an interaction between Tat and PI3 kinase PubMed
    tat Activation of protein kinase C-epsilon by HIV-1 Tat involves an interaction with PI 3-kinase PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC61518

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 1-phosphatidylinositol-3-kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables 1-phosphatidylinositol-3-kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables 1-phosphatidylinositol-3-kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables 1-phosphatidylinositol-3-kinase activity TAS
    Traceable Author Statement
    more info
     
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables phosphatidylinositol kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in autophagosome assembly IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in autophagosome assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in autophagosome maturation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acts_upstream_of_or_within autophagy IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cell division IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to glucose starvation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in early endosome to late endosome transport IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in early endosome to late endosome transport IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in endocytosis IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in macroautophagy ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in macroautophagy TAS
    Traceable Author Statement
    more info
     
    involved_in pexophagy IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in phosphatidylinositol phosphate biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in phosphatidylinositol-3-phosphate biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in phosphatidylinositol-3-phosphate biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in phosphatidylinositol-mediated signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive regulation by host of viral genome replication IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acts_upstream_of_or_within positive regulation of protein lipidation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in protein localization to phagophore assembly site IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in protein targeting to lysosome NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in regulation of autophagy IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of cytokinesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of macroautophagy IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in synaptic vesicle endocytosis IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    located_in GABA-ergic synapse IEA
    Inferred from Electronic Annotation
    more info
     
    located_in autolysosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in autophagosome IEA
    Inferred from Electronic Annotation
    more info
     
    located_in axoneme ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    is_active_in endosome IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
     
    located_in late endosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in membrane HDA PubMed 
    is_active_in membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in midbody IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in peroxisome IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in phagocytic vesicle membrane TAS
    Traceable Author Statement
    more info
     
    is_active_in phagophore assembly site IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    part_of phosphatidylinositol 3-kinase complex, class III IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    part_of phosphatidylinositol 3-kinase complex, class III ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    part_of phosphatidylinositol 3-kinase complex, class III, type I IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    part_of phosphatidylinositol 3-kinase complex, class III, type II IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in postsynaptic endosome IEA
    Inferred from Electronic Annotation
    more info
     
    located_in presynaptic endosome IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    phosphatidylinositol 3-kinase catalytic subunit type 3
    Names
    PI3-kinase type 3
    PI3K type 3
    PtdIns-3-kinase type 3
    phosphatidylinositol 3-kinase p100 subunit
    phosphoinositide-3-kinase, class 3
    vacuolar protein sorting 34 homolog
    NP_001294949.1
    NP_002638.2
    XP_047293505.1
    XP_047293506.1
    XP_047293507.1
    XP_054174667.1
    XP_054174668.1
    XP_054174669.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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.

    mRNA and Protein(s)

    1. NM_001308020.2NP_001294949.1  phosphatidylinositol 3-kinase catalytic subunit type 3 isoform 2

      See identical proteins and their annotated locations for NP_001294949.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AC087683, AK298517, CA945171, DB450556
      Consensus CDS
      CCDS77180.1
      UniProtKB/TrEMBL
      A8MYT4, B4DPV9
      Related
      ENSP00000381845.2, ENST00000398870.7
      Conserved Domains (3) summary
      cd08397
      Location:24123
      C2_PI3K_class_III; C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks)
      cd00870
      Location:220440
      PI3Ka_III; Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3Ks class III ...
      cd00896
      Location:476820
      PI3Kc_III; Catalytic domain of Class III Phosphoinositide 3-kinase
    2. NM_002647.4NP_002638.2  phosphatidylinositol 3-kinase catalytic subunit type 3 isoform 1

      See identical proteins and their annotated locations for NP_002638.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC087683, BC053651, CA945171, DB450556
      Consensus CDS
      CCDS11920.1
      UniProtKB/Swiss-Prot
      Q15134, Q8NEB9
      UniProtKB/TrEMBL
      B4DPV9
      Related
      ENSP00000262039.3, ENST00000262039.9
      Conserved Domains (3) summary
      cd08397
      Location:26186
      C2_PI3K_class_III; C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks)
      cd00870
      Location:283503
      PI3Ka_III; Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3Ks class III ...
      cd00896
      Location:539883
      PI3Kc_III; Catalytic domain of Class III Phosphoinositide 3-kinase

    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_000018.10 Reference GRCh38.p14 Primary Assembly

      Range
      41955234..42087830
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047437549.1XP_047293505.1  phosphatidylinositol 3-kinase catalytic subunit type 3 isoform X1

      UniProtKB/TrEMBL
      B4DPV9
    2. XM_047437551.1XP_047293507.1  phosphatidylinositol 3-kinase catalytic subunit type 3 isoform X3

    3. XM_047437550.1XP_047293506.1  phosphatidylinositol 3-kinase catalytic subunit type 3 isoform X2

      UniProtKB/TrEMBL
      B4DPV9

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060942.1 Alternate T2T-CHM13v2.0

      Range
      42146975..42279510
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054318692.1XP_054174667.1  phosphatidylinositol 3-kinase catalytic subunit type 3 isoform X1

      UniProtKB/TrEMBL
      B4DPV9
    2. XM_054318694.1XP_054174669.1  phosphatidylinositol 3-kinase catalytic subunit type 3 isoform X3

    3. XM_054318693.1XP_054174668.1  phosphatidylinositol 3-kinase catalytic subunit type 3 isoform X2

      UniProtKB/TrEMBL
      B4DPV9