Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0006244
UniProt IDQ8WUM4
Primary gene name(s)PDCD6IP
Synonym gene name(s)AIP1, ALIX, KIAA1375
Protein nameProgrammed cell death 6-interacting protein
Protein functionClass E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body, MVB for incorporation into intralumenal vesicles, ILVs that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid, LBPA which is abundant in MVBs internal membranes. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding, HIV-1 and other lentiviruses. Appears to be an adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis. Involved in HIV-1 virus budding. Can replace TSG101 it its role of supporting HIV-1 release; this function implies the interaction with CHMP4B. May play a role in the regulation of both apoptosis and cell proliferation. Regulates exosome biogenesis in concert with SDC1/4 and SDCBP, PubMed:22660413. {ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14739459, ECO:0000269|PubMed:17428861, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:22660413}.
Subcellular locationCytoplasm, cytosol {ECO:0000250|UniProtKB:Q9QZA2}. Melanosome {ECO:0000269|PubMed:17081065}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893}. Secreted, exosome {ECO:0000269|PubMed:22660413}. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Colocalized with CEP55 in the midbody during cytokinesis. Colocalized with CEP55 at centrosomes of non-dividing cells. {ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:17556548}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q8WUM4
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
cell cycle [GO:0007049];
cell separation after cytokinesis [GO:0000920];
multivesicular body assembly [GO:0036258];
positive regulation of exosomal secretion [GO:1903543];
positive regulation of extracellular exosome assembly [GO:1903553];
protein transport [GO:0015031];
regulation of centrosome duplication [GO:0010824];
regulation of extracellular exosome assembly [GO:1903551];
ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway [GO:0090611];
viral budding via host ESCRT complex [GO:0039702];
viral life cycle [GO:0019058]
Gene Ontology
(Molecular Function)
Complete annatation
calcium-dependent protein binding [GO:0048306];
proteinase activated receptor binding [GO:0031871];
protein homodimerization activity [GO:0042803]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endoplasmic reticulum exit site [GO:0070971];
extracellular exosome [GO:0070062];
extracellular vesicle [GO:1903561];
focal adhesion [GO:0005925];
immunological synapse [GO:0001772];
melanosome [GO:0042470];
membrane [GO:0016020];
microtubule organizing center [GO:0005815];
myelin sheath [GO:0043209]
Protein-protein interaction115332
Phylogenetic treeQ8WUM4
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD3-0.1283390480055260.6946733994248320.781818807954829
AZA vs. DISU-0.01754008905448090.9446284997150470.996198528027442
AZA vs. IL7-0.009419207681865770.9608524740151560.999311006273513
AZA vs. SAHA0.04773987722248730.8445792262857890.96311714778575
DISU vs. CD30.09808340119497250.7864117307275560.85305089005492
DISU vs. IL7-0.0009702828734943570.9969215004359280.999957156847617
DISU vs. SAHA0.06644305050642450.8193568438676020.953692976769741
DMSO vs. AZA-0.0004044667281727690.9980691969022281
DMSO vs. CD30.1169412897897660.7141956523950840.791420191491868
DMSO vs. DISU0.01546821774720610.9493642306635620.993086643946278
DMSO vs. IL7-0.001834157883869310.991845118436170.998922198828488
DMSO vs. SAHA0.04129164295957050.8607205244956250.963881633576576
HIV vs. Mock in Activation0.05127712549355170.9342789595874760.999983755607037
HIV vs. Mock in Latency0.07510215405384730.6481723514070580.999834320637052
IL7 vs. CD30.1264838338086440.6934483669763230.791702536958847
SAHA vs. CD30.1513482464841250.6678984706877860.753554686925577
SAHA vs. IL70.05334846860975240.8263283768625350.925054433047952
(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 0.00681162 0.976148
(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
1.032 0.928 0.905 0.919 0.892
(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
2OEV X-ray 3.3Å A=1-698.
2OEW X-ray 2.5Å A=1-359.
2OEX X-ray 2.5Å A/B=360-702.
2OJQ X-ray 2.8Å A=360-702.
2R02 X-ray 2.6Å A=2-698.
2R03 X-ray 2.5Å A=2-698.
2R05 X-ray 2.5Å A=2-698.
2XS1 X-ray 2.3Å A=1-698.
2XS8 X-ray 2.5Å A=1-698.
2ZNE X-ray 2.2Å C/D=799-812.
3C3O X-ray 2.1Å A=1-359.
3C3Q X-ray 2.1Å A=1-359.
3C3R X-ray 2.0Å A=1-359.
3E1R X-ray 2.0Å C=797-809.
3WUV X-ray 2.7Å C/F/I/L/O/R=796-810.
4JJY X-ray 6.5Å A/B=355-708.

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

HIV Partner Interaction Type PubMed
Pr55(Gag) incorporates 18032513
19282983
19639585
20519395
21738476
22004035
2242188024834918
p6 interacts with 18066081
18477395
22004035
2425721019282983
1940367319596386
2425721022981647
24257210
24996823
25102091
Pr55(Gag) recruits 24834918
p6 binds 14505569
14505570
14519844
16234236
16470130
17277784
17350572
17428861
17556548
17982468
18005675
19020832
19064259
19099395
19143627
19254034
19282983
19393081
19596386
19802344
21543492
22004035
22981647
23266279
2389534517277784
17350572
17982468
18005675
19254034
19282983
1959638617277784
17982468
1928298317350527
1847681018477395
Nef interacts with 25118280
25118280
Envelope surface glycoprotein gp160; precursor co-localizes with 18076669
nucleocapsid recruits 19282983
19403673
22004035
Pr55(Gag) co-localizes with 18076669
19802344
23305486
nucleocapsid binds 19403673
22896625
2389534522896625
p6 incorporates 14505569
14505570
16470130
17158451
18005675
22004035
23266279
Pr55(Gag) downregulated by 17158451
HIV-1 virus replication enhanced by expression of human gene 25633977
Pr55(Gag) interacts with 17158451
1727778419282983
19403673
20018238
22004035
22754649
23305486
2506660620519395
21762796
21762798
22421880
22761998
2330548621889351
2216275023027949
23895345
24996823
25099357
25710462
nucleocapsid incorporates 18032513
19282983
22004035
25749978
Nef co-localizes with 19912576
20156100
Pr55(Gag) binds 17277784
18005675
2154349217350572
1847681024257210
Nef binds 16764724
22844345
25118280
matrix co-localizes with 18076669
p6 rescued by 17428861

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

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