PIK3R4 phosphoinositide-3-kinase regulatory subunit 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PIK3R4provided by HGNC
Official Full Name: phosphoinositide-3-kinase regulatory subunit 4provided by HGNC
Primary source: HGNC:HGNC:8982
See related: Ensembl:ENSG00000196455 MIM:602610; AllianceGenome:HGNC:8982
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: p150; VPS15
Summary: Predicted to enable protein serine/threonine kinase activity. Involved in several processes, including early endosome to late endosome transport; phosphatidylinositol 3-kinase/protein kinase B signal transduction; and phosphatidylinositol-3-phosphate biosynthetic process. Located in late endosome and microtubule cytoskeleton. Part of phosphatidylinositol 3-kinase complex, class III. [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in thyroid (RPKM 9.2), testis (RPKM 8.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q22.1

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (130678934..130746829, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (133422776..133490673, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (130397778..130465673, complement)

Chromosome 3 - NC_000003.12 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?

Phosphoproteomic identification of ULK substrates reveals VPS15-dependent ULK/VPS34 interplay in the regulation of autophagy.
Title: Phosphoproteomic identification of ULK substrates reveals VPS15-dependent ULK/VPS34 interplay in the regulation of autophagy.
The mutations in VPS15 are associated with cortical atrophy and epilepsy in humans.
Title: Mutations in Vps15 perturb neuronal migration in mice and are associated with neurodevelopmental disease in humans.
A missense mutation in PIK3R4 (phosphoinositide 3-kinase regulatory subunit 4, named VPS15) in a family with a ciliopathy phenotype is identified. Besides being required for trafficking and autophagy, we show that VPS15 regulates primary cilium length in human fibroblasts.
Title: A mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from the cis-Golgi.
Both Danon Disease and glycogen storage disease type II show accumulation and altered localization of VPS15 in autophagy-incompetent fibers. However, TFEB displays a different pattern between these two lysosomal storage diseases
Title: Autophagy dysregulation in Danon disease.
High expression of PI3K core complex genes is associated with poor prognosis in chronic lymphocytic leukemia.
Title: High expression of PI3K core complex genes is associated with poor prognosis in chronic lymphocytic leukemia.
A specific sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates both receptor degradation and cytokinesis, whereas ATG14L, a PI3K-III subunit involved in autophagy, is not required.
Title: A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic.
hVps15, but not Ca2+/CaM, is required for the activity and regulation of hVps34 in mammalian cells
Title: hVps15, but not Ca2+/CaM, is required for the activity and regulation of hVps34 in mammalian cells.

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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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	NAS Non-traceable Author Statement more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in autophagosome maturation	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to glucose starvation	ISS Inferred from Sequence or Structural Similarity more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in early endosome to late endosome transport	IDA Inferred from Direct Assay more info	PubMed
involved_in late endosome to vacuole transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in pexophagy	IBA Inferred from Biological aspect of Ancestor more info
involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphatidylinositol-3-phosphate biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	NAS Non-traceable Author Statement more info	PubMed
involved_in protein targeting to lysosome	NAS Non-traceable Author Statement more info	PubMed
involved_in protein targeting to vacuole	IBA Inferred from Biological aspect of Ancestor more info
involved_in receptor catabolic process	IMP Inferred from Mutant Phenotype 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

Component	Evidence Code	Pubs
located_in autophagosome	IEA Inferred from Electronic Annotation more info
located_in axoneme	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
is_active_in late endosome	IBA Inferred from Biological aspect of Ancestor more info
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	HDA more info	PubMed
located_in microtubule cytoskeleton	IDA Inferred from Direct Assay more info
is_active_in nucleus-vacuole junction	IBA Inferred from Biological aspect of Ancestor more info
located_in phagocytic vesicle membrane	TAS Traceable Author Statement 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

General protein information

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Preferred Names: phosphoinositide 3-kinase regulatory subunit 4

Names: PI3-kinase p150 subunit; PI3-kinase regulatory subunit 4; phosphatidylinositol 3-kinase-associated p150; phosphoinositide 3-kinase adaptor protein; phosphoinositide-3-kinase, regulatory subunit 4, p150

NP_055417.1

EC 2.7.11.1

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_014602.3 → NP_055417.1 phosphoinositide 3-kinase regulatory subunit 4

See identical proteins and their annotated locations for NP_055417.1

Status: VALIDATED

Source sequence(s)

BP359657, Y08991

Consensus CDS

CCDS3067.1

UniProtKB/Swiss-Prot

Q2TBF4, Q99570

UniProtKB/TrEMBL

A0JP11

Related

ENSP00000349205.3, ENST00000356763.8

Conserved Domains (8) summary

smart00320
Location:1327 → 1358

WD40; WD40 repeats

smart00220
Location:26 → 309

S_TKc; Serine/Threonine protein kinases, catalytic domain

COG2319
Location:991 → 1358

WD40; WD40 repeat [General function prediction only]

cd13980
Location:25 → 320

STKc_Vps15; Catalytic domain of the Serine/Threonine kinase, Vacuolar protein sorting-associated protein 15

pfam07539
Location:352 → 448

DRIM; Down-regulated in metastasis

sd00044
Location:539 → 566

HEAT; HEAT repeat [structural motif]

sd00039
Location:997 → 1040

7WD40; WD40 repeat [structural motif]

cl02567
Location:985 → 1269

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...