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

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, Oct 2024]
Expression: Ubiquitous expression in testis (RPKM 7.2), brain (RPKM 7.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

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_000018.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Deregulated expression of autophagy genes; PIK3C3 and RAB7A in COVID-19 patients.
Title: Deregulated expression of autophagy genes; PIK3C3 and RAB7A in COVID-19 patients.
Genome-wide CRISPR/Cas9 screen identifies SLC39A9 and PIK3C3 as crucial entry factors for Ebola virus infection.
Title: Genome-wide CRISPR/Cas9 screen identifies SLC39A9 and PIK3C3 as crucial entry factors for Ebola virus infection.
PIK3C3/VPS34 keeps body fats healthy.
Title: PIK3C3/VPS34 keeps body fats healthy.
ULK1-mediated metabolic reprogramming regulates Vps34 lipid kinase activity by its lactylation.
Title: ULK1-mediated metabolic reprogramming regulates Vps34 lipid kinase activity by its lactylation.
Listeria InlB Expedites Vacuole Escape and Intracellular Proliferation by Promoting Rab7 Recruitment via Vps34.
Title: Listeria InlB Expedites Vacuole Escape and Intracellular Proliferation by Promoting Rab7 Recruitment via Vps34.
Adaptor SH3BGRL drives autophagy-mediated chemoresistance through promoting PIK3C3 translation and ATG12 stability in breast cancers.
Title: Adaptor SH3BGRL drives autophagy-mediated chemoresistance through promoting PIK3C3 translation and ATG12 stability in breast cancers.
Overcoming radio-resistance in esophageal squamous cell carcinoma via hypermethylation of PIK3C3 promoter region mediated by KDM5B loss.
Title: Overcoming radio-resistance in esophageal squamous cell carcinoma via hypermethylation of PIK3C3 promoter region mediated by KDM5B loss.
SRSF1 inhibits autophagy through regulating Bcl-x splicing and interacting with PIK3C3 in lung cancer.
Title: SRSF1 inhibits autophagy through regulating Bcl-x splicing and interacting with PIK3C3 in lung cancer.
Binding of Avibirnavirus VP3 to the PIK3C3-PDPK1 complex inhibits autophagy by activating the AKT-MTOR pathway.
Title: Binding of Avibirnavirus VP3 to the PIK3C3-PDPK1 complex inhibits autophagy by activating the AKT-MTOR pathway.
The Warburg Micro Syndrome-associated Rab3GAP-Rab18 module promotes autolysosome maturation through the Vps34 Complex I.
Title: The Warburg Micro Syndrome-associated Rab3GAP-Rab18 module promotes autolysosome maturation through the Vps34 Complex I.

Submit: New GeneRIF Correction See all GeneRIFs (75)

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

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2560 (e-PCR)
- UniSTS:37928

D18S1071 (e-PCR)
- UniSTS:42823

RH74915 (e-PCR)
- UniSTS:83803

RH91807 (e-PCR)
- UniSTS:83804

D15S1477 (e-PCR)
- UniSTS:474482

SHGC-105035 (e-PCR)
- UniSTS:169089

RH66029 (e-PCR)
- UniSTS:87231

SHGC-35582 (e-PCR)
- UniSTS:73711

RH45288 (e-PCR)
- UniSTS:70133

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 kinase activity	IDA Inferred from Direct Assay more info	PubMed
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 autophagy of peroxisome	IBA Inferred from Biological aspect of Ancestor more info
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 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 phosphorylation	IEA Inferred from Electronic Annotation 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 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 more info	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

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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

EC 2.7.1.137

NP_002638.2

EC 2.7.1.137

XP_047293505.1

EC 2.7.1.137

XP_047293506.1

EC 2.7.1.137

XP_047293507.1

EC 2.7.1.137

XP_054174667.1

EC 2.7.1.137

XP_054174668.1

EC 2.7.1.137

XP_054174669.1

EC 2.7.1.137

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.

mRNA and Protein(s)

NM_001308020.2 → NP_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:24 → 123

C2_PI3K_class_III; C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks)

cd00870
Location:220 → 440

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:476 → 820

PI3Kc_III; Catalytic domain of Class III Phosphoinositide 3-kinase
NM_002647.4 → NP_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:26 → 186

C2_PI3K_class_III; C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks)

cd00870
Location:283 → 503

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:539 → 883

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

NC_000018.10 Reference GRCh38.p14 Primary Assembly

Range

41955234..42087830

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047437549.1 → XP_047293505.1 phosphatidylinositol 3-kinase catalytic subunit type 3 isoform X1
XM_047437551.1 → XP_047293507.1 phosphatidylinositol 3-kinase catalytic subunit type 3 isoform X3
XM_047437550.1 → XP_047293506.1 phosphatidylinositol 3-kinase catalytic subunit type 3 isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060942.1 Alternate T2T-CHM13v2.0

Range

42146975..42279510

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054318692.1 → XP_054174667.1 phosphatidylinositol 3-kinase catalytic subunit type 3 isoform X1
XM_054318694.1 → XP_054174669.1 phosphatidylinositol 3-kinase catalytic subunit type 3 isoform X3
XM_054318693.1 → XP_054174668.1 phosphatidylinositol 3-kinase catalytic subunit type 3 isoform X2