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

Gene ID: 27183, updated on 17-Jun-2019

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; 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

Genomic context

See VPS4A in Genome Data Viewer
Location:
16q22.1
Exon count:
11
Annotation release Status Assembly Chr Location
109.20190607 current GRCh38.p13 (GCF_000001405.39) 16 NC_000016.10 (69311350..69326939)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (69345242..69358951)

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 FunctionsWhat'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 BioSystems

  • Budding and maturation of HIV virion, organism-specific biosystem (from REACTOME)
    Budding and maturation of HIV virion, organism-specific biosystemWith the virus components precariously assembled on the inner leaflet of the plasma membrane, the host cell machinery is required for viral budding. The virus takes advantage of the host ESCRT pathwa...
  • CXCR4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    CXCR4-mediated signaling events, organism-specific biosystem
    CXCR4-mediated signaling events
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Endocytosis, organism-specific biosystem (from KEGG)
    Endocytosis, organism-specific biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
  • Endocytosis, conserved biosystem (from KEGG)
    Endocytosis, conserved biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
  • Endosomal Sorting Complex Required For Transport (ESCRT), organism-specific biosystem (from REACTOME)
    Endosomal Sorting Complex Required For Transport (ESCRT), organism-specific biosystemMany plasma membrane proteins are in a constant flux throughout the internal trafficking pathways of the cell. Some receptors are continuously internalized into recycling endosomes and returned to th...
  • HIV Infection, organism-specific biosystem (from REACTOME)
    HIV Infection, organism-specific biosystemThe global pandemic of Human Immunodeficiency Virus (HIV) infection has resulted in tens of millions of people infected by the virus and millions more affected. UNAIDS estimates around 40 million ...
  • HIV Life Cycle, organism-specific biosystem (from REACTOME)
    HIV Life Cycle, organism-specific biosystemThe life cycle of HIV-1 is divided into early and late phases, shown schematically in the figure. In the early phase, an HIV-1 virion binds to receptors and co-receptors on the human host cell surfac...
  • Infectious disease, organism-specific biosystem (from REACTOME)
    Infectious disease, organism-specific biosystem
    Infectious disease
  • Late Phase of HIV Life Cycle, organism-specific biosystem (from REACTOME)
    Late Phase of HIV Life Cycle, organism-specific biosystemThe late phase of the HIV-1 life cycle includes the regulated expression of the HIV gene products and the assembly of viral particles. The assembly of viral particles will be covered in a later relea...
  • Membrane Trafficking, organism-specific biosystem (from REACTOME)
    Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...
  • Vesicle-mediated transport, organism-specific biosystem (from REACTOME)
    Vesicle-mediated transport, organism-specific biosystemThe transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclo...

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
ATP binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
ATPase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ATPase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
ATPase activity NAS
Non-traceable Author Statement
more info
PubMed 
ATPase activity, coupled NAS
Non-traceable Author Statement
more info
PubMed 
protein C-terminus binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein domain specific binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein-containing complex binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
ESCRT III complex disassembly NAS
Non-traceable Author Statement
more info
PubMed 
ESCRT complex disassembly NAS
Non-traceable Author Statement
more info
PubMed 
abscission IMP
Inferred from Mutant Phenotype
more info
PubMed 
actomyosin contractile ring contraction TAS
Traceable Author Statement
more info
PubMed 
cell division IDA
Inferred from Direct Assay
more info
PubMed 
cytoskeleton-dependent cytokinesis TAS
Traceable Author Statement
more info
PubMed 
endosomal transport IMP
Inferred from Mutant Phenotype
more info
PubMed 
endosomal transport TAS
Traceable Author Statement
more info
 
endosomal vesicle fusion IMP
Inferred from Mutant Phenotype
more info
PubMed 
intracellular cholesterol transport IMP
Inferred from Mutant Phenotype
more info
PubMed 
late endosomal microautophagy ISS
Inferred from Sequence or Structural Similarity
more info
 
macroautophagy NAS
Non-traceable Author Statement
more info
PubMed 
midbody abscission IMP
Inferred from Mutant Phenotype
more info
PubMed 
mitotic cytokinesis checkpoint IMP
Inferred from Mutant Phenotype
more info
PubMed 
mitotic metaphase plate congression IMP
Inferred from Mutant Phenotype
more info
PubMed 
multivesicular body assembly ISS
Inferred from Sequence or Structural Similarity
more info
 
multivesicular body assembly NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of cytokinesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
nuclear envelope organization TAS
Traceable Author Statement
more info
PubMed 
nuclear envelope reassembly TAS
Traceable Author Statement
more info
PubMed 
nucleus organization IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of exosomal secretion IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of viral budding via host ESCRT complex IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of viral life cycle IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of viral release from host cell IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein targeting to lysosome IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of protein localization IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of protein localization to plasma membrane IMP
Inferred from Mutant Phenotype
more info
PubMed 
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
vacuole organization IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
vesicle budding from membrane IMP
Inferred from Mutant Phenotype
more info
PubMed 
vesicle uncoating IMP
Inferred from Mutant Phenotype
more info
PubMed 
vesicle-mediated transport IDA
Inferred from Direct Assay
more info
PubMed 
viral budding via host ESCRT complex IGI
Inferred from Genetic Interaction
more info
PubMed 
viral life cycle TAS
Traceable Author Statement
more info
 
viral release from host cell IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
Flemming body IDA
Inferred from Direct Assay
more info
PubMed 
centrosome IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
early endosome IDA
Inferred from Direct Assay
more info
PubMed 
endosome IDA
Inferred from Direct Assay
more info
PubMed 
endosome membrane IMP
Inferred from Mutant Phenotype
more info
PubMed 
extracellular exosome HDA PubMed 
late endosome IDA
Inferred from Direct Assay
more info
PubMed 
late endosome membrane IEA
Inferred from Electronic Annotation
more info
 
lysosome IDA
Inferred from Direct Assay
more info
PubMed 
midbody IDA
Inferred from Direct Assay
more info
PubMed 
colocalizes_with midbody TAS
Traceable Author Statement
more info
PubMed 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
spindle pole IDA
Inferred from Direct Assay
more info
PubMed 
vacuolar membrane IDA
Inferred from Direct Assay
more info
PubMed 

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)

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 (2) summary
    COG0464
    Location:26348
    SpoVK; AAA+-type ATPase, SpoVK/Ycf46/Vps4 family [Cell wall/membrane/envelope biogenesis, Cell cycle control, cell division, chromosome partitioning, Signal transduction mechanisms]
    pfam09336
    Location:374434
    Vps4_C; Vps4 C terminal oligomerization domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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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