Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001976
UniProt IDO60936
Primary gene name(s)NOL3
Synonym gene name(s)ARC, NOP
Protein nameNucleolar protein 3
Protein functionIsoform 1: May be involved in RNA splicing. {ECO:0000269|PubMed:10196175}.; FUNCTION: Isoform 2: Functions as an apoptosis repressor that blocks multiple modes of cell death. Inhibits extrinsic apoptotic pathways through two different ways. Firstly by interacting with FAS and FADD upon FAS activation blocking death-inducing signaling complex, DISC assembly, By similarity. Secondly by interacting with CASP8 in a mitochondria localization- and phosphorylation-dependent manner, limiting the amount of soluble CASP8 available for DISC-mediated activation, By similarity. Inhibits intrinsic apoptotic pathway in response to a wide range of stresses, through its interaction with BAX resulting in BAX inactivation, preventing mitochondrial dysfunction and release of pro-apoptotic factors, PubMed:15004034. Inhibits calcium-mediated cell death by functioning as a cytosolic calcium buffer, dissociating its interaction with CASP8 and maintaining calcium homeostasis, PubMed:15509781. Negatively regulates oxidative stress-induced apoptosis by phosphorylation-dependent suppression of the mitochondria-mediated intrinsic pathway, by blocking CASP2 activation and BAX translocation, By similarity. Negatively regulates hypoxia-induced apoptosis in part by inhibiting the release of cytochrome c from mitochondria in a caspase-independent manner, By similarity. Also inhibits TNF-induced necrosis by preventing TNF-signaling pathway through TNFRSF1A interaction abrogating the recruitment of RIPK1 to complex I, By similarity. Finally through its role as apoptosis repressor, promotes vascular remodeling through inhibition of apoptosis and stimulation of proliferation, in response to hypoxia, By similarity. Inhibits too myoblast differentiation through caspase inhibition, By similarity. {ECO:0000250|UniProtKB:Q62881, ECO:0000250|UniProtKB:Q9D1X0, ECO:0000269|PubMed:15004034, ECO:0000269|PubMed:15509781}.
Subcellular locationIsoform 1: Nucleus, nucleolus {ECO:0000269|PubMed:10196175}. Note=The SR-rich C-terminus mediates nuclear localization. {ECO:0000269|PubMed:10196175}.;
SUBCELLULAR LOCATION: Isoform 3: Cytoplasm {ECO:0000305}.;
SUBCELLULAR LOCATION: Isoform 2: Cytoplasm {ECO:0000269|PubMed:10196175}. Mitochondrion {ECO:0000250|UniProtKB:Q62881}. Sarcoplasmic reticulum {ECO:0000250|UniProtKB:Q62881}. Membrane {ECO:0000305};
Lipid-anchor {ECO:0000305}. Note=Phosphorylation at Thr-149 results in translocation to mithochondria. Colocalized with mitochondria in response to oxidative stress. {ECO:0000250|UniProtKB:Q62881}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O60936
Gene Ontology
(Biological Process)
Complete annatation
blood vessel remodeling [GO:0001974];
cardiac muscle cell apoptotic process [GO:0010659];
inhibition of cysteine-type endopeptidase activity involved in apoptotic process [GO:1990001];
intrinsic apoptotic signaling pathway [GO:0097193];
mRNA splice site selection [GO:0006376];
negative regulation of apoptotic process [GO:0043066];
negative regulation of cardiac muscle cell apoptotic process [GO:0010667];
negative regulation of extrinsic apoptotic signaling pathway [GO:2001237];
negative regulation of mitochondrial membrane permeability involved in apoptotic process [GO:1902109];
negative regulation of muscle atrophy [GO:0014736];
negative regulation of necrotic cell death [GO:0060547];
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway [GO:1902176];
negative regulation of release of cytochrome c from mitochondria [GO:0090201];
negative regulation of tumor necrosis factor-mediated signaling pathway [GO:0010804];
protein oligomerization [GO:0051259];
regulation of NF-kappaB import into nucleus [GO:0042345];
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum [GO:0014808];
response to hypoxia [GO:0001666];
response to injury involved in regulation of muscle adaptation [GO:0014876];
response to ischemia [GO:0002931];
RNA splicing [GO:0008380]
Gene Ontology
(Molecular Function)
Complete annatation
calcium ion binding [GO:0005509];
caspase binding [GO:0089720];
cysteine-type endopeptidase inhibitor activity involved in apoptotic process [GO:0043027];
identical protein binding [GO:0042802];
RNA binding [GO:0003723]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
membrane [GO:0016020];
mitochondrion [GO:0005739];
nucleolus [GO:0005730];
sarcoplasmic reticulum [GO:0016529]
Protein-protein interaction114477
Phylogenetic treeO60936
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. CD3-1.97074564292043.10867909081303e-072.69591251043687e-06
AZA vs. DISU0.6110540561563040.01741812176382030.317445587148874
AZA vs. IL7-0.02091844875472150.9284958379072210.999311006273513
AZA vs. SAHA0.01010992142238950.9672673758070920.991228805411965
DISU vs. CD32.566528913076477.59605711664335e-111.90520740393148e-09
DISU vs. IL7-0.6420076640610560.01189787977999590.130392136690677
DISU vs. SAHA-0.5976057263297790.04322909071460780.258124257591067
DMSO vs. AZA-0.01782882490210140.932456330657981
DMSO vs. CD31.944748504867953.16586513005035e-072.49053567541559e-06
DMSO vs. DISU-0.6297832120458890.01088375230018590.224682393375071
DMSO vs. IL70.003856302581815850.9855166662733230.998499429186965
DMSO vs. SAHA0.02197337735482540.926459582063070.982780458369212
HIV vs. Mock in Activation0.5149319554459440.4952570756384510.999983755607037
HIV vs. Mock in Latency0.1199884122663180.5731350592863590.999834320637052
IL7 vs. CD31.953842266997914.35063352566267e-074.56983269214728e-06
SAHA vs. CD31.95745302373431.5633445138441e-071.5479370449166e-06
SAHA vs. IL70.02868150789840080.9071056912619780.964635710058769
(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) 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 0.810163 0.257823
(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
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
4UZ0 X-ray 2.4Å A/B=1-95.

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

HIV Partner Interaction Type PubMed
HIV-1 virus replication enhanced by expression of human gene 18976975

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
not found