Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0007840
UniProt IDQ9UN37
Primary gene name(s)VPS4A
Synonym gene name(s)VPS4
Protein nameVacuolar protein sorting-associated protein 4A
Protein functionInvolved in late steps of the endosomal multivesicular bodies, MVB pathway. Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly, possibly in combination with membrane fission. Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. MVBs contain intraluminal vesicles, ILVs that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. In conjunction with the ESCRT machinery also appears to function in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding, HIV-1 and other lentiviruses. Involved in cytokinesis: retained at the midbody by ZFYVE19/ANCHR and CHMP4C until abscission checkpoint signaling is terminated at late cytokinesis. It is then released following dephosphorylation of CHMP4C, leading to abscission, PubMed:24814515. VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan, PubMed:22660413. {ECO:0000269|PubMed:11563910, ECO:0000269|PubMed:11595185, ECO:0000269|PubMed:15075231, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:24814515}.
Subcellular locationPrevacuolar compartment membrane;
Peripheral membrane protein. Late endosome membrane {ECO:0000305};
Peripheral membrane protein {ECO:0000305}. Midbody. Note=Membrane-associated in the prevacuolar endosomal compartment. Localizes to the midbody of dividing cells, interaction with ZFYVE19/ANCHR mediates retention at midbody, PubMed:24814515. Localized in two distinct rings on either side of the Flemming body. {ECO:0000269|PubMed:24814515}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9UN37
Gene Ontology
(Biological Process)
Complete annatation
abscission [GO:0009838];
autophagy [GO:0006914];
cell division [GO:0051301];
cell separation after cytokinesis [GO:0000920];
endosomal transport [GO:0016197];
endosomal vesicle fusion [GO:0034058];
ESCRT complex disassembly [GO:1904896];
ESCRT III complex disassembly [GO:1904903];
intracellular cholesterol transport [GO:0032367];
late endosomal microautophagy [GO:0061738];
membrane budding [GO:0006900];
mitotic metaphase plate congression [GO:0007080];
multivesicular body assembly [GO:0036258];
negative regulation of cytokinesis [GO:0032466];
nucleus organization [GO:0006997];
positive regulation of exosomal secretion [GO:1903543];
positive regulation of viral budding via host ESCRT complex [GO:1903774];
positive regulation of viral life cycle [GO:1903902];
positive regulation of viral release from host cell [GO:1902188];
protein transport [GO:0015031];
regulation of protein localization [GO:0032880];
regulation of protein localization to plasma membrane [GO:1903076];
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway [GO:0043162];
ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway [GO:0090611];
vacuole organization [GO:0007033];
vesicle-mediated transport [GO:0016192];
vesicle uncoating [GO:0072319];
viral budding via host ESCRT complex [GO:0039702];
viral life cycle [GO:0019058];
viral release from host cell [GO:0019076]
Gene Ontology
(Molecular Function)
Complete annatation
ATPase activity [GO:0016887];
ATPase activity, coupled [GO:0042623];
ATP binding [GO:0005524];
protein C-terminus binding [GO:0008022];
protein domain specific binding [GO:0019904]
Gene Ontology
(Cellular Component)
Complete annatation
centrosome [GO:0005813];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
early endosome [GO:0005769];
endosome [GO:0005768];
extracellular exosome [GO:0070062];
Flemming body [GO:0090543];
late endosome [GO:0005770];
late endosome membrane [GO:0031902];
lysosome [GO:0005764];
midbody [GO:0030496];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471];
plasma membrane [GO:0005886];
spindle pole [GO:0000922];
vacuolar membrane [GO:0005774]
Protein-protein interaction118059
Phylogenetic treeQ9UN37
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      Yes - Two siRNA pools inhibit HIV replication and inhibition of Tat-mediated transactivation of the HIV LTR is not observed
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.4485482677239480.1711799330683530.270356741978476
AZA vs. DISU0.08490482647274380.7372119181199360.974591756386051
AZA vs. IL70.08940804484960710.6421903656185210.999311006273513
AZA vs. SAHA-0.1997309488795330.4134261631748970.768432303785253
DISU vs. CD3-0.3763805923886730.2996686112013880.430907626180456
DISU vs. IL7-0.004870602347526130.9845736944344270.997754944136459
DISU vs. SAHA-0.2823554733709680.3327281125122040.712082843608644
DMSO vs. AZA0.08123178351971840.6283127188786181
DMSO vs. CD3-0.3800664857002430.2348836965222330.339003917235816
DMSO vs. DISU-0.005851318400860110.9808649004880150.99735766500781
DMSO vs. IL70.01565279591776460.9306763395765110.986634727082694
DMSO vs. SAHA-0.2863164330952250.2250611013074080.571251110585826
HIV vs. Mock in Activation-0.0005381018940607470.9993104691688190.999983755607037
HIV vs. Mock in Latency0.00577024920070010.9721497782450230.999834320637052
IL7 vs. CD3-0.3527543837931490.2723397912714420.407441952737911
SAHA vs. CD3-0.6719986926538280.05815614142198090.112216779926921
SAHA vs. IL7-0.2917389539757570.2314054935648070.472144884948011
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change -1.228964508
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.0645003 0.7156
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.972 0.997 1.005 1.076 0.963
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1YXR NMR - A=1-77.
2JQ9 NMR - A=1-84.
2K3W NMR - A=1-84.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Pr55(Gag) inhibited by 20427536
Pr55(Gag) recruits 25099357
p1 inhibits 21248205
Pr55(Gag) co-localizes with 21394083
Pr55(Gag) associates with 20164219
Pr55(Gag) regulated by 24107264
Vpu cooperates with 21304933
Nef requires 19403684
HIV-1 virus replication enhanced by expression of human gene 18976975
Pr55(Gag) recruited by 21394083

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04144 Endocytosis - Homo sapiens (human)