Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000642
UniProt IDP10909
Primary gene name(s)CLU
Synonym gene name(s)APOJ, CLI, KUB1
Protein nameClusterin
Protein functionIsoform 1 functions as extracellular chaperone that prevents aggregation of nonnative proteins. Prevents stress-induced aggregation of blood plasma proteins. Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants, in vitro. Does not require ATP. Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70. Does not refold proteins by itself. Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation. Secreted isoform 1 protects cells against apoptosis and against cytolysis by complement. Intracellular isoforms interact with ubiquitin and SCF, SKP1-CUL1-F-box protein E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes proteasomal degradation of COMMD1 and IKBKB. Modulates NF-kappa-B transcriptional activity. Nuclear isoforms promote apoptosis. Mitochondrial isoforms suppress BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis. Plays a role in the regulation of cell proliferation. {ECO:0000269|PubMed:11123922, ECO:0000269|PubMed:12047389, ECO:0000269|PubMed:12176985, ECO:0000269|PubMed:12551933, ECO:0000269|PubMed:12882985, ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:17407782, ECO:0000269|PubMed:17412999, ECO:0000269|PubMed:17689225, ECO:0000269|PubMed:19137541, ECO:0000269|PubMed:19535339, ECO:0000269|PubMed:19996109, ECO:0000269|PubMed:20068069, ECO:0000269|PubMed:21505792}.
Subcellular locationIsoform 1: Secreted. Note=Can retrotranslocate from the secretory compartments to the cytosol upon cellular stress.;
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Mitochondrion membrane;
Peripheral membrane protein;
Cytoplasmic side. Cytoplasm, cytosol. Microsome. Endoplasmic reticulum. Cytoplasmic vesicle, secretory vesicle, chromaffin granule {ECO:0000250}. Note=Isoforms lacking the N-terminal signal sequence have been shown to be cytoplasmic and/or nuclear. Secreted isoforms can retrotranslocate from the secretory compartments to the cytosol upon cellular stress. Detected in perinuclear foci that may be aggresomes containing misfolded, ubiquitinated proteins. Detected at the mitochondrion membrane upon induction of apoptosis.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P10909
Gene Ontology
(Biological Process)
Complete annatation
cell morphogenesis [GO:0000902];
central nervous system myelin maintenance [GO:0032286];
chaperone-mediated protein complex assembly [GO:0051131];
chaperone-mediated protein folding [GO:0061077];
complement activation [GO:0006956];
complement activation, classical pathway [GO:0006958];
innate immune response [GO:0045087];
intrinsic apoptotic signaling pathway [GO:0097193];
lipid metabolic process [GO:0006629];
microglial cell activation [GO:0001774];
microglial cell proliferation [GO:0061518];
negative regulation of beta-amyloid formation [GO:1902430];
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage [GO:1902230];
negative regulation of protein homooligomerization [GO:0032463];
platelet degranulation [GO:0002576];
positive regulation of apoptotic process [GO:0043065];
positive regulation of beta-amyloid formation [GO:1902004];
positive regulation of intrinsic apoptotic signaling pathway [GO:2001244];
positive regulation of neurofibrillary tangle assembly [GO:1902998];
positive regulation of neuron death [GO:1901216];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of nitric oxide biosynthetic process [GO:0045429];
positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436];
positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:2000060];
positive regulation of tau-protein kinase activity [GO:1902949];
positive regulation of tumor necrosis factor production [GO:0032760];
protein import [GO:0017038];
protein stabilization [GO:0050821];
regulation of beta-amyloid clearance [GO:1900221];
regulation of neuronal signal transduction [GO:1902847];
regulation of neuron death [GO:1901214];
release of cytochrome c from mitochondria [GO:0001836];
response to misfolded protein [GO:0051788];
response to virus [GO:0009615];
reverse cholesterol transport [GO:0043691]
Gene Ontology
(Molecular Function)
Complete annatation
chaperone binding [GO:0051087];
misfolded protein binding [GO:0051787];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
aggresome [GO:0016235];
apical dendrite [GO:0097440];
blood microparticle [GO:0072562];
cell surface [GO:0009986];
chromaffin granule [GO:0042583];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endoplasmic reticulum [GO:0005783];
extracellular exosome [GO:0070062];
extracellular matrix [GO:0031012];
extracellular region [GO:0005576];
extracellular space [GO:0005615];
Golgi apparatus [GO:0005794];
growth cone [GO:0030426];
intracellular [GO:0005622];
mitochondrial membrane [GO:0031966];
mitochondrion [GO:0005739];
neurofibrillary tangle [GO:0097418];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471];
platelet alpha granule lumen [GO:0031093];
protein complex [GO:0043234];
spherical high-density lipoprotein particle [GO:0034366]
Protein-protein interaction107603
Phylogenetic treeP10909
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. CD3-1.728523950424431.44250245126543e-058.60257426074264e-05
AZA vs. DISU0.9229629429658160.003709756304467570.156641082727014
AZA vs. IL7-0.1536254007838630.4457867715707360.999311006273513
AZA vs. SAHA-0.2109650288337720.5270774626535640.836938310948048
DISU vs. CD32.638992425199033.71135120857957e-073.96706286299447e-06
DISU vs. IL7-1.08644829379390.001618000944654030.0373383300375478
DISU vs. SAHA-1.132899903680860.01732746443550090.147927944259974
DMSO vs. AZA-0.02389203652252480.8930326604337241
DMSO vs. CD31.689400940038922.57529249506616e-050.000134275235107795
DMSO vs. DISU-0.9497434247754580.003288832111040920.123468133417415
DMSO vs. IL7-0.1219470077347590.517766376328470.889301967358611
DMSO vs. SAHA-0.1932758776708740.5736757444193370.851920641282627
HIV vs. Mock in Activation0.08600595613565580.9241346862894770.999983755607037
HIV vs. Mock in Latency0.1319249470799520.738603579373510.999834320637052
IL7 vs. CD31.582511733896030.0001538261855476010.000849001133196261
SAHA vs. CD31.491154515080140.005127773418627910.0145913038932633
SAHA vs. IL7-0.06153201422556130.864688252931710.943820462042602
(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
-1.9 0.063741592 -2.1 0.027884346 -2.1 0.082497889
(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) TRUE
(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 0.7344 0.000305467
(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
unknown unknown unknown unknown unknown
(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
208791_at 2.47 No downregulated in CD8+ cells
208792_s_at 2.19 No downregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

not found

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

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04610 Complement and coagulation cascades - Homo sapiens (human)