Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003254
UniProt IDQ93009
Primary gene name(s)USP7
Synonym gene name(s)HAUSP
Protein nameUbiquitin carboxyl-terminal hydrolase 7
Protein functionHydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN and DAXX, PubMed:11923872, PubMed:15053880, PubMed:16964248, PubMed:18716620, PubMed:25283148. Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation. Deubiquitinates p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis, PubMed:25283148. Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis. Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity. In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML. Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair, TC-NER in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6. Contributes to the overall stabilization and trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection. Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1, PubMed:21745816. Exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Increases regulatory T-cells, Treg suppressive capacity by deubiquitinating and stabilizing the transcription factor FOXP3 which is crucial for Treg cell function, PubMed:23973222. {ECO:0000269|PubMed:11923872, ECO:0000269|PubMed:14506283, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:16160161, ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:18590780, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:20153724, ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:22411829, ECO:0000269|PubMed:22466611, ECO:0000269|PubMed:22466612, ECO:0000269|PubMed:22689415, ECO:0000269|PubMed:23973222, ECO:0000269|PubMed:25283148}.
Subcellular locationNucleus {ECO:0000269|PubMed:23973222, ECO:0000269|PubMed:25283148}. Cytoplasm {ECO:0000269|PubMed:25283148}. Nucleus, PML body {ECO:0000269|PubMed:9034339}. Note=Present in a minority of ND10 nuclear bodies. Association with ICP0/VMW110 at early times of infection leads to an increased proportion of USP7-containing ND10. Colocalizes with ATXN1 in the nucleus. Colocalized with DAXX in speckled structures. Colocalized with PML and PTEN in promyelocytic leukemia protein, PML nuclear bodies.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q93009
Gene Ontology
(Biological Process)
Complete annatation
maintenance of DNA methylation [GO:0010216];
multicellular organism development [GO:0007275];
negative regulation of NF-kappaB transcription factor activity [GO:0032088];
protein deubiquitination [GO:0016579];
protein stabilization [GO:0050821];
regulation of sequence-specific DNA binding transcription factor activity [GO:0051090];
regulation of telomere capping [GO:1904353];
transcription-coupled nucleotide-excision repair [GO:0006283];
ubiquitin-dependent protein catabolic process [GO:0006511];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
cysteine-type endopeptidase activity [GO:0004197];
p53 binding [GO:0002039];
protein C-terminus binding [GO:0008022];
thiol-dependent ubiquitin-specific protease activity [GO:0004843];
transcription factor binding [GO:0008134];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
nuclear body [GO:0016604];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
PML body [GO:0016605]
Protein-protein interaction113622
Phylogenetic treeQ93009
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. CD30.4508863497973140.1689646908852890.267588086689406
AZA vs. DISU0.01355599219530090.9572076011071670.996649735504266
AZA vs. IL70.07329530353151120.7023322589619590.999311006273513
AZA vs. SAHA-0.003452110671145120.988687835288750.997555584279961
DISU vs. CD3-0.4501279608520380.2159880002737430.338038833476746
DISU vs. IL70.05079096434529910.8399942241253970.966339509210192
DISU vs. SAHA-0.0157218509786060.9569535728255010.990061919404485
DMSO vs. AZA-0.003533180980165570.9831237766809491
DMSO vs. CD3-0.4660853518283110.1454595561125880.231325684876611
DMSO vs. DISU-0.0190157333274380.9378003457364760.991915896991669
DMSO vs. IL70.08412380948751520.6390492550867820.921661837625646
DMSO vs. SAHA-0.006723026973753410.9772056914255630.994628687477183
HIV vs. Mock in Activation0.1318813319137910.8321379921455040.999983755607037
HIV vs. Mock in Latency0.03482829388863760.8323304856413760.999834320637052
IL7 vs. CD3-0.3698467452936830.2500011064154230.381751258940296
SAHA vs. CD3-0.4794449812098610.1750524015906980.272468466429645
SAHA vs. IL7-0.08049266082971190.7405631157311530.881929144354372
(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) FALSE
(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 -0.398122 0.00221059
(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 0.962 0.932 0.876 0.971
(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
1NB8 X-ray 2.3Å A/B=208-560.
1NBF X-ray 2.3Å A/B/E=208-560.
1YY6 X-ray 1.7Å A=54-204.
1YZE X-ray 2.0Å A/B/C=54-205.
2F1W X-ray 1.6Å A=53-206.
2F1X X-ray 2.3Å A/B=53-200.
2F1Y X-ray 1.7Å A=53-198.
2F1Z X-ray 3.2Å A/B=43-560.
2FOJ X-ray 1.6Å A=54-205.
2FOO X-ray 2.2Å A=54-205.
2FOP X-ray 2.1Å A=54-205.
2KVR NMR - A=537-664.
2XXN X-ray 1.6Å A=63-205.
2YLM X-ray 2.7Å A=560-1084.
3MQR X-ray 1.8Å A=54-205.
3MQS X-ray 2.4Å C=54-205.
4JJQ X-ray 1.9Å A=54-205.
4KG9 X-ray 1.7Å A=54-205.
4M5W X-ray 2.2Å A=207-560.
4M5X X-ray 2.1Å A/B=207-560.
4PYZ X-ray 2.8Å A/B=537-793.
4WPH X-ray 2.9Å A/B=535-888.
4WPI X-ray 3.4Å A/B=535-888.
4YOC X-ray 2.9Å C=560-1102.
4YSI X-ray 1.0Å A=63-205.
4Z96 X-ray 2.8Å A=560-1083.
4Z97 X-ray 3.0Å A=560-1083.
5C56 X-ray 2.6Å A=560-1102.
5C6D X-ray 2.2Å A/B=561-881.
5FWI X-ray 3.4Å C=207-882.
5J7T X-ray 3.2Å A=211-881.
5JTJ X-ray 3.3Å A=209-554# A=1084-1102.
5JTV X-ray 3.3Å A/C/E/G=207-554# A/C/E/G=882-1102.

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
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)