Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0007312
UniProt IDQ9UNE7
Primary gene name(s)STUB1
Synonym gene name(s)CHIP
Protein nameE3 ubiquitin-protein ligase CHIP
Protein functionE3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation. Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. Ubiquitinates NOS1 in concert with Hsp70 and Hsp40. Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90. Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation. Mediates polyubiquitination of DNA polymerase beta, POLB at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome. Mediates polyubiquitination of CYP3A4. Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation. Negatively regulates the suppressive function of regulatory T-cells, Treg during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner, PubMed:23973223. {ECO:0000269|PubMed:10330192, ECO:0000269|PubMed:11146632, ECO:0000269|PubMed:11557750, ECO:0000269|PubMed:15466472, ECO:0000269|PubMed:19103148, ECO:0000269|PubMed:19567782, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:23990462}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:10330192, ECO:0000269|PubMed:23973223}. Nucleus {ECO:0000269|PubMed:23973223}. Note=Translocates to the nucleus in response to inflammatory signals in regulatory T-cells, Treg. {ECO:0000269|PubMed:23973223}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9UNE7
Gene Ontology
(Biological Process)
Complete annatation
cellular response to misfolded protein [GO:0071218];
DNA repair [GO:0006281];
endoplasmic reticulum unfolded protein response [GO:0030968];
ERBB2 signaling pathway [GO:0038128];
misfolded or incompletely synthesized protein catabolic process [GO:0006515];
negative regulation of protein binding [GO:0032091];
negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512];
positive regulation of chaperone-mediated protein complex assembly [GO:0090035];
positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436];
positive regulation of protein ubiquitination [GO:0031398];
positive regulation of ubiquitin-protein transferase activity [GO:0051443];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein autoubiquitination [GO:0051865];
protein K63-linked ubiquitination [GO:0070534];
protein maturation [GO:0051604];
protein polyubiquitination [GO:0000209];
protein ubiquitination [GO:0016567];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
regulation of glucocorticoid metabolic process [GO:0031943];
regulation of protein stability [GO:0031647];
ubiquitin-dependent protein catabolic process [GO:0006511];
ubiquitin-dependent SMAD protein catabolic process [GO:0030579]
Gene Ontology
(Molecular Function)
Complete annatation
enzyme binding [GO:0019899];
G-protein coupled receptor binding [GO:0001664];
Hsp70 protein binding [GO:0030544];
Hsp90 protein binding [GO:0051879];
kinase binding [GO:0019900];
ligase activity [GO:0016874];
misfolded protein binding [GO:0051787];
protein binding, bridging [GO:0030674];
protein homodimerization activity [GO:0042803];
SMAD binding [GO:0046332];
TPR domain binding [GO:0030911];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin protein ligase activity involved in ERAD pathway [GO:1904264];
ubiquitin protein ligase binding [GO:0031625];
ubiquitin-protein transferase activity [GO:0004842];
ubiquitin-ubiquitin ligase activity [GO:0034450]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endoplasmic reticulum [GO:0005783];
extracellular exosome [GO:0070062];
intermediate filament cytoskeleton [GO:0045111];
nuclear inclusion body [GO:0042405];
nucleoplasm [GO:0005654];
plasma membrane [GO:0005886];
ubiquitin conjugating enzyme complex [GO:0031371];
ubiquitin ligase complex [GO:0000151];
Z disc [GO:0030018]
Protein-protein interaction115563
Phylogenetic treeQ9UNE7
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. CD30.327458958579670.3188372254338740.438699530923805
AZA vs. DISU-0.0179903688141420.9435287427709050.996198528027442
AZA vs. IL7-0.06218392016647570.7481200576634830.999311006273513
AZA vs. SAHA0.1143630742113240.641025336060320.889170648267383
DISU vs. CD3-0.3572372292483040.3275612223451930.460559450203473
DISU vs. IL7-0.05390946162086220.8310508929561160.964589982005358
DISU vs. SAHA0.1346811797756310.6463649598048640.890761366973218
DMSO vs. AZA0.02795405174649690.8687132297166871
DMSO vs. CD3-0.3123874091647240.3304718757868010.444355480964669
DMSO vs. DISU0.04370191448892420.8583227161143230.984172509503272
DMSO vs. IL7-0.08247287022820410.6488143719704970.924835160992995
DMSO vs. SAHA0.08163035799088570.7307077441535030.921387247641323
HIV vs. Mock in Activation0.03775146622437530.9519209628311140.999983755607037
HIV vs. Mock in Latency0.01461210875514140.9301895333225080.999834320637052
IL7 vs. CD3-0.3841408506786460.2344467480843650.363782604912746
SAHA vs. CD3-0.235891186567260.5045862063453660.613333935281873
SAHA vs. IL70.1739953247378870.4782301642299890.711001232429515
(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 -0.17096 0.660331
(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
0.988 0.911 0.987 1.097 1.013
(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
4KBQ X-ray 2.9Å A/B=21-154.

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

HIV Partner Interaction Type PubMed
Vif interacts with 22190034

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)