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

Gene ID: 27183, updated on 8-Jul-2021

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
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
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Genomic context

See VPS4A in Genome Data Viewer
Location:
16q22.1
Exon count:
11
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 16 NC_000016.10 (69311350..69326939)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (69345253..69360842)

Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene RNA, U6 small nuclear 22, pseudogene Neighboring gene syntrophin beta 2 Neighboring gene zinc finger CCHC-type and RNA binding motif containing 1 pseudogene Neighboring gene component of oligomeric golgi complex 8 Neighboring gene peptide deformylase, mitochondrial Neighboring gene nucleolar pre-rRNA processing protein NIP7 Neighboring gene transmembrane p24 trafficking protein 6

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?

HIV-1 interactions

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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ22197

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
PubMed 
enables ATP hydrolysis activity IEA
Inferred from Electronic Annotation
more info
 
enables ATP hydrolysis activity IMP
Inferred from Mutant Phenotype
more info
 
enables protein C-terminus binding IDA
Inferred from Direct Assay
more info
PubMed 
enables protein C-terminus binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables protein disaggregase activity NAS
Non-traceable Author Statement
more info
PubMed 
enables protein domain specific 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 abscission IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in actomyosin contractile ring contraction TAS
Traceable Author Statement
more info
PubMed 
involved_in cell division IDA
Inferred from Direct Assay
more info
PubMed 
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
PubMed 
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 macroautophagy NAS
Non-traceable Author Statement
more info
PubMed 
involved_in midbody abscission IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in mitotic cytokinesis checkpoint signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in mitotic metaphase plate congression 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 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 TAS
Traceable Author Statement
more info
PubMed 
involved_in nucleus organization IMP
Inferred from Mutant Phenotype
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 positive regulation of viral life cycle IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of viral release from host cell 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
PubMed 
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 
Component Evidence Code Pubs
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 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 
colocalizes_with midbody TAS
Traceable Author Statement
more info
PubMed 
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
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 spindle pole IDA
Inferred from Direct Assay
more info
PubMed 
located_in vacuolar membrane IDA
Inferred from Direct Assay
more info
 

General protein information

Preferred Names
vacuolar protein sorting-associated protein 4A
Names
SKD1-homolog
hVPS4
vacuolar protein sorting factor 4A
vacuolar sorting protein 4
NP_037377.1

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)

  1. NM_013245.3NP_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
    Q9UN37
    UniProtKB/TrEMBL
    A0A024R705
    Related
    ENSP00000254950.11, ENST00000254950.13
    Conserved Domains (3) summary
    PTZ00454
    Location:4348
    PTZ00454; 26S protease regulatory subunit 6B-like protein; Provisional
    pfam09336
    Location:374434
    Vps4_C; Vps4 C terminal oligomerization domain
    cd19521
    Location:121291
    RecA-like_VPS4; ATPase domain of vacuolar protein sorting-associated protein 4

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000016.10 Reference GRCh38.p13 Primary Assembly

    Range
    69311350..69326939
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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