Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002360
UniProt IDP61289
Primary gene name(s)PSME3
Synonym gene name(s)unknown
Protein nameProteasome activator complex subunit 3
Protein functionSubunit of the 11S REG-gamma, also called PA28-gamma proteasome regulator, a doughnut-shaped homoheptamer which associates with the proteasome. 11S REG-gamma activates the trypsin-like catalytic subunit of the proteasome but inhibits the chymotrypsin-like and postglutamyl-preferring, PGPH subunits. Facilitates the MDM2-p53/TP53 interaction which promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53, limiting its accumulation and resulting in inhibited apoptosis after DNA damage. May also be involved in cell cycle regulation. Mediates CCAR2 and CHEK2-dependent SIRT1 inhibition, PubMed:25361978. {ECO:0000269|PubMed:10835274, ECO:0000269|PubMed:11185562, ECO:0000269|PubMed:11432824, ECO:0000269|PubMed:15111123, ECO:0000269|PubMed:18309296, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:9325261}.
Subcellular locationNucleus {ECO:0000269|PubMed:10657252, ECO:0000269|PubMed:12629132}. Cytoplasm {ECO:0000250}. Note=Localizes to the cytoplasm during mitosis following nuclear envelope breakdown at this distinct stage of the cell cycle which allows its interaction with MAP3K3 kinase. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P61289
Gene Ontology
(Biological Process)
Complete annatation
anaphase-promoting complex-dependent catabolic process [GO:0031145];
antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent [GO:0002479];
apoptotic process [GO:0006915];
Fc-epsilon receptor signaling pathway [GO:0038095];
MAPK cascade [GO:0000165];
negative regulation of canonical Wnt signaling pathway [GO:0090090];
negative regulation of extrinsic apoptotic signaling pathway [GO:2001237];
negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle [GO:0051436];
NIK/NF-kappaB signaling [GO:0038061];
positive regulation of canonical Wnt signaling pathway [GO:0090263];
positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition [GO:0051437];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein polyubiquitination [GO:0000209];
regulation of cellular amino acid metabolic process [GO:0006521];
regulation of G1/S transition of mitotic cell cycle [GO:2000045];
regulation of mRNA stability [GO:0043488];
regulation of proteasomal protein catabolic process [GO:0061136];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
T cell receptor signaling pathway [GO:0050852];
tumor necrosis factor-mediated signaling pathway [GO:0033209];
Wnt signaling pathway, planar cell polarity pathway [GO:0060071]
Gene Ontology
(Molecular Function)
Complete annatation
endopeptidase activator activity [GO:0061133];
identical protein binding [GO:0042802];
MDM2/MDM4 family protein binding [GO:0097371];
p53 binding [GO:0002039]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
membrane [GO:0016020];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
proteasome activator complex [GO:0008537];
proteasome complex [GO:0000502]
Protein-protein interaction115492
Phylogenetic treeP61289
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. CD31.592175438372042.05947062070777e-061.49089054732505e-05
AZA vs. DISU0.04578675450071670.8562698112504860.989951370113767
AZA vs. IL70.2877976130521830.1344180455509120.898662602392564
AZA vs. SAHA-0.1170787811616760.6311628213657770.883858531253332
DISU vs. CD3-1.559017850967052.57768209460663e-050.000171096344756056
DISU vs. IL70.2325711027723770.3556474840052010.734235253544016
DISU vs. SAHA-0.1607366892965460.5809233038324020.865147684815138
DMSO vs. AZA0.03155898304554950.8505556281368871
DMSO vs. CD3-1.572115247644951.58083182832947e-061.08944334372294e-05
DMSO vs. DISU-0.01612403973560760.94728228371710.993012243712903
DMSO vs. IL70.2635448195610170.1426849583019890.644970238801344
DMSO vs. SAHA-0.1543409553509770.5126057756963850.820505404616239
HIV vs. Mock in Activation0.0738057086448340.905427157553850.999983755607037
HIV vs. Mock in Latency-0.03055926671847580.8532129469049720.999834320637052
IL7 vs. CD3-1.297867603933567.0204120537265e-050.000428762847997648
SAHA vs. CD3-1.732658622918771.81684176225883e-061.38913269189449e-05
SAHA vs. IL7-0.4071281634003780.09481074101421540.278833040751648
(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 0.239205 0.0777558
(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
0.981 1.055 1.006 0.906 1.04
(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

not found

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

HIV Partner Interaction Type PubMed
Tat enhances 9079628
Tat inhibits 14550573
Vif interacts with 22190034
integrase degraded by 10893419
HIV-1 virus replication enhanced by expression of human gene 19460752
Tat interacts with 12419264

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03050 Proteasome - Homo sapiens (human)
hsa04612 Antigen processing and presentation - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)