Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0007815
UniProt IDP55072
Primary gene name(s)VCP
Synonym gene name(s)unknown
Protein nameTransitional endoplasmic reticulum ATPase
Protein functionNecessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum, tER. The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum, tER. Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1L, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1L-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A. Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation, ERAD of HMGCR. Also involved in DNA damage response: recruited to double-strand breaks, DSBs sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites. Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta, POLH to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage. Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation. Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy, PubMed:20104022. {ECO:0000250|UniProtKB:P46462, ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:20104022, ECO:0000269|PubMed:21118995, ECO:0000269|PubMed:22020440, ECO:0000269|PubMed:22120668, ECO:0000269|PubMed:22607976, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607}.
Subcellular locationCytoplasm, cytosol. Endoplasmic reticulum. Nucleus. Note=Present in the neuronal hyaline inclusion bodies specifically found in motor neurons from amyotrophic lateral sclerosis patients. Present in the Lewy bodies specifically found in neurons from Parkinson disease patients. Recruited to the cytoplasmic surface of the endoplasmic reticulum via interaction with AMFR/gp78. Following DNA double-strand breaks, recruited to the sites of damage. Recruited to stalled replication forks via interaction with SPRTN.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P55072
Gene Ontology
(Biological Process)
Complete annatation
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919];
aggresome assembly [GO:0070842];
ATP metabolic process [GO:0046034];
autophagosome maturation [GO:0097352];
autophagy [GO:0006914];
cellular response to DNA damage stimulus [GO:0006974];
DNA repair [GO:0006281];
double-strand break repair [GO:0006302];
endoplasmic reticulum unfolded protein response [GO:0030968];
ERAD pathway [GO:0036503];
ER-associated misfolded protein catabolic process [GO:0071712];
ER-associated ubiquitin-dependent protein catabolic process [GO:0030433];
error-free translesion synthesis [GO:0070987];
ER to Golgi vesicle-mediated transport [GO:0006888];
establishment of protein localization [GO:0045184];
flavin adenine dinucleotide catabolic process [GO:0072389];
NADH metabolic process [GO:0006734];
positive regulation of ATP biosynthetic process [GO:2001171];
positive regulation of Lys63-specific deubiquitinase activity [GO:1903007];
positive regulation of mitochondrial membrane potential [GO:0010918];
positive regulation of oxidative phosphorylation [GO:1903862];
positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436];
positive regulation of protein catabolic process [GO:0045732];
positive regulation of protein complex assembly [GO:0031334];
positive regulation of protein K63-linked deubiquitination [GO:1903006];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein hexamerization [GO:0034214];
protein homooligomerization [GO:0051260];
protein N-linked glycosylation via asparagine [GO:0018279];
protein ubiquitination [GO:0016567];
regulation of aerobic respiration [GO:1903715];
regulation of apoptotic process [GO:0042981];
retrograde protein transport, ER to cytosol [GO:0030970];
translesion synthesis [GO:0019985];
viral genome replication [GO:0019079]
Gene Ontology
(Molecular Function)
Complete annatation
ADP binding [GO:0043531];
ATPase activity [GO:0016887];
ATP binding [GO:0005524];
BAT3 complex binding [GO:1904288];
deubiquitinase activator activity [GO:0035800];
lipid binding [GO:0008289];
poly(A RNA binding [GO:0044822];
polyubiquitin binding [GO:0031593];
protein domain specific binding [GO:0019904];
protein phosphatase binding [GO:0019903];
ubiquitin-like protein ligase binding [GO:0044389];
ubiquitin protein ligase binding [GO:0031625];
ubiquitin-specific protease binding [GO:1990381]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
Derlin-1 retrotranslocation complex [GO:0036513];
endoplasmic reticulum [GO:0005783];
endoplasmic reticulum membrane [GO:0005789];
extracellular exosome [GO:0070062];
intracellular membrane-bounded organelle [GO:0043231];
lipid particle [GO:0005811];
myelin sheath [GO:0043209];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471];
proteasome complex [GO:0000502];
site of double-strand break [GO:0035861];
VCP-NPL4-UFD1 AAA ATPase complex [GO:0034098];
VCP-NSFL1C complex [GO:1990730]
Protein-protein interaction113258
Phylogenetic treeP55072
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
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. CD31.225473767286880.0002312057321748330.00100831388754024
AZA vs. DISU0.8686628487430090.0006688602939619590.0589614039250443
AZA vs. IL70.139686642186420.4662837670063520.999311006273513
AZA vs. SAHA-0.01680209108711840.9449982605954830.988903162234032
DISU vs. CD3-0.3708298575385310.3140995594538510.446631144156904
DISU vs. IL7-0.738194253599780.00363778045889440.0616115741611483
DISU vs. SAHA-0.8827120984314340.002634427697338130.04131473447095
DMSO vs. AZA0.02444926851230760.8835838496908931
DMSO vs. CD3-1.212049722506240.0001878162602719780.000785740616772382
DMSO vs. DISU-0.8460928329321320.0005996776967632790.0485867897323796
DMSO vs. IL70.1225696597323150.494238267308170.885378142451182
DMSO vs. SAHA-0.04728261862097020.8408876911078120.957417400056551
HIV vs. Mock in Activation0.0823454857006750.8945339904894850.999983755607037
HIV vs. Mock in Latency-0.003025602066612520.9853267698782010.999834320637052
IL7 vs. CD3-1.079271322000690.0009061090961792750.0038977689516867
SAHA vs. CD3-1.266110507663650.000448352351998360.00178310179150038
SAHA vs. IL7-0.1591322482759970.512967903386230.737644422363469
(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 unknown
(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 -0.178356 0.213641
(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
1.001 1.039 1.124 1.181 1.016
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
3EBB X-ray 1.9Å E/F/G/H=797-806.
3HU1 X-ray 2.8Å A/B/C/D/E/F=1-481.
3HU2 X-ray 2.8Å A/B/C/D/E/F=1-481.
3HU3 X-ray 2.2Å A/B=1-481.
3QC8 X-ray 2.2Å A=21-196.
3QQ7 X-ray 2.6Å A=2-187.
3QQ8 X-ray 2.0Å A=2-187.
3QWZ X-ray 2.0Å A=1-208.
3TIW X-ray 1.8Å A/B=1-187.
4KDI X-ray 1.8Å A/B=21-196.
4KDL X-ray 1.8Å A=21-196.
4KLN X-ray 2.6Å A/B/C/D/E/F=1-481.
4KO8 X-ray 1.9Å A/B=1-481.
4KOD X-ray 2.9Å A/B/C/D/E/F/G/H/I/J/K/L=1-481.
4P0A X-ray 2.3Å B/D=797-806.
5C18 X-ray 3.3Å A/B/C/D/E/F=2-806.
5C19 X-ray 4.2Å A/B/C/D/E/F=2-806.
5C1A X-ray 3.8Å A/B/C/D/E/F/G/H/I/J/K/L=2-806.
5C1B X-ray 3.0Å A/B/C/D/E/F=2-806.
5DYG X-ray 2.2Å A=1-460.
5DYI X-ray 3.7Å A/B/C/D/E/F/G/H/I/J/K/L=1-481.
5EPP X-ray 1.8Å A=21-199.
5FTJ EM 2.3Å A/B/C/D/E/F=1-806.
5FTK EM 2.4Å A/B/C/D/E/F=1-806.
5FTL EM 3.3Å A/B/C/D/E/F=1-806.
5FTM EM 3.2Å A/B/C/D/E/F=1-806.
5FTN EM 3.3Å A/B/C/D/E/F=1-806.

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

HIV Partner Interaction Type PubMed
Envelope transmembrane glycoprotein gp41 interacts with 22190034
Vpu cooperates with 19730691

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)
hsa05134 Legionellosis - Homo sapiens (human)