VPS4A vacuolar protein sorting 4 homolog A [Homo sapiens (human)] - Gene

Summary

Official Symbol: VPS4Aprovided by HGNC
Official Full Name: vacuolar protein sorting 4 homolog Aprovided by HGNC
Primary source: HGNC:HGNC:13488
See related: Ensembl:ENSG00000132612 MIM:609982; AllianceGenome:HGNC:13488
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: SKD1; SKD2; VPS4; SKD1A; CIMDAG; VPS4-1
Summary: The protein encoded by this gene is a member of the AAA protein family (ATPases associated with diverse cellular activities), and is the homolog of the yeast Vps4 protein. In humans, two paralogs of the yeast protein have been identified. The former share a high degree of aa sequence similarity with each other, and also with yeast Vps4 and mouse Skd1 proteins. The mouse Skd1 (suppressor of K+ transport defect 1) has been shown to be really an yeast Vps4 ortholog. Functional studies indicate that both human paralogs associate with the endosomal compartments, and are involved in intracellular protein trafficking, similar to Vps4 protein in yeast. The gene encoding this paralog has been mapped to chromosome 16; the gene for the other resides on chromosome 18. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in brain (RPKM 45.1), fat (RPKM 36.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16q22.1

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (69311350..69326939)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (75113104..75128634)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (69345253..69360842)

Chromosome 16 - NC_000016.10 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The human AAA-ATPase VPS4A isoform and its co-factor VTA1 have a unique function in regulating mammalian cytokinesis abscission.
Title: The human AAA-ATPase VPS4A isoform and its co-factor VTA1 have a unique function in regulating mammalian cytokinesis abscission.
CHMP4B and VSP4A reverse GSDMD-mediated pyroptosis by cell membrane remodeling in endometrial carcinoma.
Title: CHMP4B and VSP4A reverse GSDMD-mediated pyroptosis by cell membrane remodeling in endometrial carcinoma.
Analysis of individual HIV-1 budding event using fast AFM reveals a multiplexed role for VPS4.
Title: Analysis of individual HIV-1 budding event using fast AFM reveals a multiplexed role for VPS4.
The ESCRT-III protein VPS4, but not CHMP4B or CHMP2B, is pathologically increased in familial and sporadic ALS neuronal nuclei.
Title: The ESCRT-III protein VPS4, but not CHMP4B or CHMP2B, is pathologically increased in familial and sporadic ALS neuronal nuclei.
Synthetic Lethal Interaction between the ESCRT Paralog Enzymes VPS4A and VPS4B in Cancers Harboring Loss of Chromosome 18q or 16q.
Title: Synthetic Lethal Interaction between the ESCRT Paralog Enzymes VPS4A and VPS4B in Cancers Harboring Loss of Chromosome 18q or 16q.
Vaccinia virus hijacks ESCRT-mediated multivesicular body formation for virus egress.
Title: Vaccinia virus hijacks ESCRT-mediated multivesicular body formation for virus egress.
Synthetic lethality between VPS4A and VPS4B triggers an inflammatory response in colorectal cancer.
Title: Synthetic lethality between VPS4A and VPS4B triggers an inflammatory response in colorectal cancer.
VPS4A mutation in syndromic congenital hemolytic anemia without obvious signs of dyserythropoiesis.
Title: VPS4A mutation in syndromic congenital hemolytic anemia without obvious signs of dyserythropoiesis.
De Novo VPS4A Mutations Cause Multisystem Disease with Abnormal Neurodevelopment.
Title: De Novo VPS4A Mutations Cause Multisystem Disease with Abnormal Neurodevelopment.
VPS4A Mutations in Humans Cause Syndromic Congenital Dyserythropoietic Anemia due to Cytokinesis and Trafficking Defects.
Title: VPS4A Mutations in Humans Cause Syndromic Congenital Dyserythropoietic Anemia due to Cytokinesis and Trafficking Defects.

Submit: New GeneRIF Correction See all GeneRIFs (43)

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
Cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome MedGen: C5543287 OMIM: 619273 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)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 incorporates VPS4A and CHMP4b into virions	PubMed
HIV-1 replication requires VPS4A function as expression of a dominant negative VPS4A (DE228Q) decreased Gag VLP production	PubMed
HIV-1 replication is inhibited by overexpression of VPS4A in HEK293T cells	PubMed
Knockdown of vacuolar protein sorting 4 homolog A (VPS4A) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	HIV-1 Nef targets CD4 to CD63-containing lysosomes for Nef-induced degradation of CD4, which requires the VPS4-mediated ESCRT machinery	PubMed
Pr55(Gag)	gag	Expressing a dominant negative mutant of VSP4A E228Q or silencing VSP4A by siRNA upregulate the amount of HIV-1 Gag on the plasma membrane and downregulate release of Gag virus-like particles	PubMed
	gag	CHMP4B and VPS4A are recruited to the site of HIV-1 Gag assembly, in which VPS4A remains associated with the Gag assembly site twice longer than CHMP4B	PubMed
	gag	VPS4A/B proteins are recruited to assist with membrane fission after full assembly of HIV-1 Gag into the VLP	PubMed
	gag	ALIX, CHMP2A/B, CHMP4A/B, and VPS4A/B proteins are required for the budding of HIV-1 Gag and the HIV-1 infectivity	PubMed
	gag	VPS4A increases co-localization of HIV-1 Gag with the ESCRT proteins Chmp1b, Chmp4b, and Chmp4c at sites of HIV-1 assembly	PubMed
	gag	Replacing the NC-p1-p6 region of HIV-1 Gag with the leucine zipper domain of yeast GCN4 overcomes inhibition of HIV-1 particle budding by dominant-negative ESCRT proteins such as CHMP3 and Vps4A	PubMed
	gag	ISG15 inhibits budding of HIV-1 by disrupting the association between Vps4 and the Gag budding complex	PubMed
	gag	VPS4A is co-localized with nascent HIV-1 Gag molecules at the host cell plasma membrane by using live-cell imaging	PubMed
Vpu	vpu	The v-ATPase VPS4 is required for Vpu-induced cell surface downregulation of BST-2. VPS4 E223/Q mutant impairs the ability of Vpu to downregulate BST-2 from the cell surface	PubMed
p1	gag	The budding defect of p6-deficient HIV-1 Gag is caused primarily by C-terminal exposure of p1, which activates a cis-acting inhibitory budding signal (IBS) and impairs an exosomes and microvesicles (EMV) cargo-VPS4 interaction	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

RH69710 (e-PCR)
- UniSTS:81742

D21S1698 (e-PCR)
- UniSTS:150410

D20S994 (e-PCR)
- UniSTS:154613

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IMP Inferred from Mutant Phenotype more info
enables ATP hydrolysis activity	IBA Inferred from Biological aspect of Ancestor more info
enables ATP hydrolysis activity	IMP Inferred from Mutant Phenotype more info
enables ATP hydrolysis activity	TAS Traceable Author Statement more info
enables ATP-dependent H2AZ histone chaperone activity	IEA Inferred from Electronic Annotation more info
enables ATP-dependent H3-H4 histone complex chaperone activity	IEA Inferred from Electronic Annotation more info
enables ATP-dependent protein disaggregase activity	NAS Non-traceable Author Statement more info	PubMed
enables DNA clamp loader activity	IEA Inferred from Electronic Annotation more info
enables chromatin extrusion motor activity	IEA Inferred from Electronic Annotation more info
enables cohesin loader activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in ESCRT III complex disassembly	NAS Non-traceable Author Statement more info	PubMed
involved_in ESCRT complex disassembly	NAS Non-traceable Author Statement more info	PubMed
involved_in actomyosin contractile ring contraction	TAS Traceable Author Statement more info	PubMed
involved_in autophagosome maturation	NAS Non-traceable Author Statement more info	PubMed
involved_in autophagy	NAS Non-traceable Author Statement more info	PubMed
involved_in cell division	IDA Inferred from Direct Assay more info	PubMed
involved_in chromatin looping	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in cytoskeleton-dependent cytokinesis	TAS Traceable Author Statement more info	PubMed
involved_in endosomal transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in endosomal transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endosomal vesicle fusion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular cholesterol transport	IMP Inferred from Mutant Phenotype more info
involved_in late endosomal microautophagy	ISS Inferred from Sequence or Structural Similarity more info
involved_in late endosome to lysosome transport via multivesicular body sorting pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in macroautophagy	NAS Non-traceable Author Statement more info	PubMed
involved_in membrane fission	NAS Non-traceable Author Statement more info	PubMed
involved_in midbody abscission	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in midbody abscission	NAS Non-traceable Author Statement more info	PubMed
involved_in mitotic cytokinesis checkpoint signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitotic metaphase chromosome alignment	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitotic nuclear membrane reassembly	TAS Traceable Author Statement more info
involved_in multivesicular body assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in multivesicular body assembly	NAS Non-traceable Author Statement more info	PubMed
involved_in multivesicular body sorting pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of cytokinesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nuclear envelope organization	TAS Traceable Author Statement more info	PubMed
involved_in nuclear membrane reassembly	NAS Non-traceable Author Statement more info	PubMed
involved_in nuclear membrane reassembly	TAS Traceable Author Statement more info	PubMed
involved_in nucleus organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nucleus organization	NAS Non-traceable Author Statement more info	PubMed
involved_in plasma membrane repair	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of exosomal secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of viral budding via host ESCRT complex	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein targeting to lysosome	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein localization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vacuole organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in vesicle budding from membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vesicle uncoating	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vesicle-mediated transport	IDA Inferred from Direct Assay more info	PubMed
involved_in viral budding from plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in viral budding via host ESCRT complex	IGI Inferred from Genetic Interaction more info	PubMed
involved_in viral release from host cell	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of ATPase complex	NAS Non-traceable Author Statement more info	PubMed
located_in Flemming body	IDA Inferred from Direct Assay more info	PubMed
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
located_in late endosome membrane	IEA Inferred from Electronic Annotation more info
located_in lysosome	IDA Inferred from Direct Assay more info
located_in midbody	IDA Inferred from Direct Assay more info	PubMed
located_in midbody	NAS Non-traceable Author Statement more info	PubMed
colocalizes_with midbody	TAS Traceable Author Statement more info	PubMed
part_of nuclear pore	NAS Non-traceable Author Statement more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in spindle pole	IDA Inferred from Direct Assay more info	PubMed
located_in vacuolar membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: vacuolar protein sorting-associated protein 4A

Names: SKD1-homolog; hVPS4; vacuolar protein sorting factor 4A; vacuolar sorting protein 4

NP_037377.1

EC 3.6.4.6

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_013245.3 → NP_037377.1 vacuolar protein sorting-associated protein 4A

See identical proteins and their annotated locations for NP_037377.1

Status: REVIEWED

Source sequence(s)

AC026464, AF255952

Consensus CDS

CCDS45517.1

UniProtKB/Swiss-Prot

B2RCB7, Q8TF07, Q9UI03, Q9UN37, Q9Y582

UniProtKB/TrEMBL

A0AAQ5BI89

Related

ENSP00000254950.11, ENST00000254950.13

Conserved Domains (3) summary

PTZ00454
Location:4 → 348

PTZ00454; 26S protease regulatory subunit 6B-like protein; Provisional

pfam09336
Location:374 → 434

Vps4_C; Vps4 C terminal oligomerization domain

cd19521
Location:121 → 291

RecA-like_VPS4; ATPase domain of vacuolar protein sorting-associated protein 4