Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0007796
UniProt IDP40818
Primary gene name(s)USP8
Synonym gene name(s)KIAA0055, UBPY
Protein nameUbiquitin carboxyl-terminal hydrolase 8
Protein functionHydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the M phase. Involved in cell proliferation. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and OTUB1. Probably regulates the stability of STAM2 and RASGRF1. Regulates endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early endosomes, and maintenance of ESCRT-0 stability. The level of protein ubiquitination on endosomes is essential for maintaining the morphology of the organelle. Deubiquitinates EPS15 and controles tyrosine kinase stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR degradation and downstream MAPK signaling. Involved in acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1. {ECO:0000269|PubMed:16520378, ECO:0000269|PubMed:17711858, ECO:0000269|PubMed:18329369, ECO:0000269|PubMed:9628861}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:16520378, ECO:0000269|PubMed:17711858, ECO:0000269|PubMed:19427866}. Nucleus {ECO:0000250|UniProtKB:Q80U87}. Endosome membrane {ECO:0000269|PubMed:16520378, ECO:0000269|PubMed:17711858};
Peripheral membrane protein {ECO:0000305}. Cell membrane {ECO:0000269|PubMed:16520378};
Peripheral membrane protein {ECO:0000305}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P40818
Gene Ontology
(Biological Process)
Complete annatation
cell proliferation [GO:0008283];
endosome organization [GO:0007032];
ERBB2 signaling pathway [GO:0038128];
mitotic cytokinesis [GO:0000281];
protein deubiquitination [GO:0016579];
protein K48-linked deubiquitination [GO:0071108];
protein K63-linked deubiquitination [GO:0070536];
ubiquitin-dependent protein catabolic process [GO:0006511]
Gene Ontology
(Molecular Function)
Complete annatation
cysteine-type endopeptidase activity [GO:0004197];
thiol-dependent ubiquitin-specific protease activity [GO:0004843]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
early endosome [GO:0005769];
extrinsic component of endosome membrane [GO:0031313];
extrinsic component of plasma membrane [GO:0019897];
Golgi apparatus [GO:0005794];
midbody [GO:0030496];
nucleoplasm [GO:0005654]
Protein-protein interaction114555
Phylogenetic treeP40818
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. CD30.3926974304359670.2310833277027380.3412588590178
AZA vs. DISU0.2804584091669590.2680531411057770.843267472087723
AZA vs. IL70.08224958403513070.6692124366474040.999311006273513
AZA vs. SAHA0.0124166533408220.9594500728039640.990779256780515
DISU vs. CD3-0.1251946184981750.7294732345158850.810160023379173
DISU vs. IL7-0.2072051276658190.4107859215685920.76991882918678
DISU vs. SAHA-0.2667549195822760.3612970017138160.736470125211859
DMSO vs. AZA-0.04207310976381020.8021242820647831
DMSO vs. CD3-0.4455353463480920.1642631648986480.255142239323449
DMSO vs. DISU-0.3241414315968290.1845754904237120.700203440443708
DMSO vs. IL70.1313872675151150.4656636334309580.876252870495513
DMSO vs. SAHA0.04747022595328680.8405977613475440.95720807414196
HIV vs. Mock in Activation-0.0871448425123490.8886773978406540.999983755607037
HIV vs. Mock in Latency0.05223307244060850.7518405466612120.999834320637052
IL7 vs. CD3-0.3025756445635620.3462278905708020.483704976788738
SAHA vs. CD3-0.4052851337207150.2531629311352360.362934301009134
SAHA vs. IL7-0.07323833382688630.7641283743366250.894878711439799
(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 -0.195662 0.381508
(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
0.969 0.955 0.848 0.852 0.943
(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
1WHB NMR - A=174-317.
2A9U X-ray 2.1Å A/B=1-142.
2GFO X-ray 2.0Å A=734-1110.
2GWF X-ray 2.3Å A/C/E=181-318.
3N3K X-ray 2.6Å A=734-1110.

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
hsa04144 Endocytosis - Homo sapiens (human)