Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002569
UniProt IDQ9NQC3
Primary gene name(s)RTN4
Synonym gene name(s)KIAA0886, NOGO
Protein nameReticulon-4
Protein functionDevelopmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS. Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex, By similarity. Isoform 2 reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration. Isoform 2 and isoform 3 inhibit BACE1 activity and amyloid precursor protein processing. Induces the formation and stabilization of endoplasmic reticulum, ER tubules, PubMed:25612671, PubMed:24262037. Regulates membrane morphogenesis in the ER by promoting tubular ER production. Influences NE expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins, PubMed:26906412. {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:10667797, ECO:0000269|PubMed:11201742, ECO:0000269|PubMed:16965550, ECO:0000269|PubMed:24262037, ECO:0000269|PubMed:25612671, ECO:0000269|PubMed:26906412}.
Subcellular locationEndoplasmic reticulum membrane {ECO:0000269|PubMed:25612671, ECO:0000269|PubMed:26906412};
Multi-pass membrane protein {ECO:0000255}. Note=Anchored to the membrane of the endoplasmic reticulum through 2 putative transmembrane domains. Co-localizes with TMEM33 at the ER sheets. {ECO:0000269|PubMed:25612671}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9NQC3
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
axonal fasciculation [GO:0007413];
cardiac epithelial to mesenchymal transition [GO:0060317];
cerebral cortex radial glia guided migration [GO:0021801];
endoplasmic reticulum tubular network assembly [GO:0071787];
endoplasmic reticulum tubular network organization [GO:0071786];
negative regulation of axon extension [GO:0030517];
negative regulation of axonogenesis [GO:0050771];
negative regulation of cell growth [GO:0030308];
nuclear pore complex assembly [GO:0051292];
regulation of apoptotic process [GO:0042981];
regulation of branching morphogenesis of a nerve [GO:2000172];
regulation of cell migration [GO:0030334]
Gene Ontology
(Molecular Function)
Complete annatation
poly(A RNA binding [GO:0044822]
Gene Ontology
(Cellular Component)
Complete annatation
endoplasmic reticulum [GO:0005783];
endoplasmic reticulum membrane [GO:0005789];
extracellular exosome [GO:0070062];
integral component of endoplasmic reticulum membrane [GO:0030176];
intracellular [GO:0005622];
neuronal postsynaptic density [GO:0097481];
nuclear envelope [GO:0005635];
plasma membrane [GO:0005886]
Protein-protein interaction121400
Phylogenetic treeQ9NQC3
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. CD3-0.1459516176986930.6598433622516940.753706643111597
AZA vs. DISU0.08042485469605650.7504699858817450.976021571236163
AZA vs. IL70.06693626930118180.7277327323936130.999311006273513
AZA vs. SAHA0.009771126269766820.9680920133046450.991238894753038
DISU vs. CD30.2136530492970140.5623209961861050.679708156066365
DISU vs. IL7-0.02303229824553220.9271476004474630.986390893149553
DISU vs. SAHA-0.06897112002697430.8128037202546310.95143627687997
DMSO vs. AZA-0.06170427660340740.7128139216890021
DMSO vs. CD30.07493592681859060.8171578333918240.871353536243476
DMSO vs. DISU-0.1435784191590490.5561140051550450.923981810005217
DMSO vs. IL70.1356544311633550.4507685090134330.870037488432936
DMSO vs. SAHA0.06445444464957210.7847456763051080.939533582941956
HIV vs. Mock in Activation0.06773608623334340.9164004066548120.999983755607037
HIV vs. Mock in Latency0.07742212125427920.6389802662166570.999834320637052
IL7 vs. CD30.219791785274140.4983043645628920.62860035562043
SAHA vs. CD30.131291008166060.7167497611484760.79415717596196
SAHA vs. IL7-0.06040299264831490.8045084870804260.91474098251258
(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 -0.528283 0.00605069
(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
1.021 1.071 1.087 1.177 0.964
(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
2G31 NMR - A=1055-1114.
2JV5 NMR - A=1055-1108.

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

HIV Partner Interaction Type PubMed
Vpu interacts with 22190034
Vpr downregulates 23874603

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa05010 Alzheimer's disease - Homo sapiens (human)