Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0007834
UniProt IDQ96QK1
Primary gene name(s)VPS35
Synonym gene name(s)MEM3
Protein nameVacuolar protein sorting-associated protein 35
Protein functionActs as component of the retromer cargo-selective complex, CSC. The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network, TGN and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5, Probable. Required for retrograde transport of lysosomal enzyme receptor IGF2R and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor, pIgR-pIgA, PubMed:15078903, PubMed:15247922, PubMed:20164305. Required for endosomal localization of FAM21C, PubMed:22070227. Mediates the association of the CSC with the WASH complex via FAM21, PubMed:22070227, PubMed:24980502, PubMed:24819384. Required for the endosomal localization of TBC1D5, PubMed:20923837. {ECO:0000269|PubMed:15078903, ECO:0000269|PubMed:15247922, ECO:0000269|PubMed:20164305, ECO:0000269|PubMed:20923837, ECO:0000269|PubMed:22070227, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24819384, ECO:0000269|PubMed:24980502, ECO:0000303|PubMed:21725319, ECO:0000303|PubMed:22070227, ECO:0000303|PubMed:22513087, ECO:0000303|PubMed:23563491}.
Subcellular locationCytoplasm. Membrane;
Peripheral membrane protein. Endosome {ECO:0000269|PubMed:15078903}. Early endosome {ECO:0000305}. Late endosome {ECO:0000305}. Note=Localizes to tubular profiles adjacent to endosomes. {ECO:0000269|PubMed:15078903}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q96QK1
Gene Ontology
(Biological Process)
Complete annatation
intracellular protein transport [GO:0006886];
mitochondrial fragmentation involved in apoptotic process [GO:0043653];
mitochondrion to lysosome transport [GO:0099074];
negative regulation of late endosome to lysosome transport [GO:1902823];
neurotransmitter receptor transport, endosome to plasma membrane [GO:0099639];
positive regulation of canonical Wnt signaling pathway [GO:0090263];
positive regulation of cellular protein catabolic process [GO:1903364];
positive regulation of dopamine receptor signaling pathway [GO:0060161];
positive regulation of gene expression [GO:0010628];
positive regulation of mitochondrial fission [GO:0090141];
positive regulation of Wnt protein secretion [GO:0061357];
regulation of cellular protein metabolic process [GO:0032268];
regulation of dendritic spine maintenance [GO:1902950];
regulation of macroautophagy [GO:0016241];
regulation of mitochondrion organization [GO:0010821];
regulation of protein stability [GO:0031647];
regulation of terminal button organization [GO:2000331];
retrograde transport, endosome to Golgi [GO:0042147];
retrograde transport, endosome to plasma membrane [GO:1990126];
transcytosis [GO:0045056];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
protein transporter activity [GO:0008565]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
early endosome [GO:0005769];
endosome [GO:0005768];
extracellular exosome [GO:0070062];
late endosome [GO:0005770];
lysosomal membrane [GO:0005765];
neuronal postsynaptic density [GO:0097481];
retromer, cargo-selective complex [GO:0030906];
retromer complex [GO:0030904];
tubular endosome [GO:0097422]
Protein-protein interaction120855
Phylogenetic treeQ96QK1
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. CD30.5793576199929410.07737090641161630.142454715543108
AZA vs. DISU0.253124992659150.3168267391857820.869223884097826
AZA vs. IL70.2386503338400520.2142620163928720.980640565974075
AZA vs. SAHA0.1185436691286460.6269170308444280.881132617524373
DISU vs. CD3-0.3393347137659640.3489387125097460.482604106098899
DISU vs. IL7-0.02341922211354890.9258363742831280.986022837026695
DISU vs. SAHA-0.1333543398621340.6474160475820190.891335222691649
DMSO vs. AZA-0.03195824234504240.8486216944056091
DMSO vs. CD3-0.6230409318363640.05190749230784220.0993755714344444
DMSO vs. DISU-0.2870364859905660.2393824854890840.756203026523891
DMSO vs. IL70.277873428741910.122151295315170.614720681909546
DMSO vs. SAHA0.1437522702389010.5419087658435830.834750181711649
HIV vs. Mock in Activation-0.1464162686402770.8138373629902380.999983755607037
HIV vs. Mock in Latency0.04550572996317980.782581166335680.999834320637052
IL7 vs. CD3-0.3325779979403440.300257088496790.438077155639542
SAHA vs. CD3-0.4858970684743860.1697858110417610.265891320004088
SAHA vs. IL7-0.1235416903893280.6119150739191820.804299940130906
(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 -0.067714 0.703674
(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
0.994 0.967 0.983 1.011 0.995
(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
217727_x_at 1.41 No upregulated in CD8+ cells

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
2R17 X-ray 2.8Å C/D=483-780.

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

HIV Partner Interaction Type PubMed
Envelope transmembrane glycoprotein gp41 binds 25393110
Tat upregulates 23166591

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

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