Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002641
UniProt IDP58004
Primary gene name(s)SESN2
Synonym gene name(s)Hi95, SEST2
Protein nameSestrin-2
Protein functionFunctions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling, PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26612684, PubMed:26586190. Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway, PubMed:26449471, PubMed:26586190. This stress-inducible metabolic regulator also plays a role in protection against oxidative and genotoxic stresses. May negatively regulate protein translation in response to endoplasmic reticulum stress, via TORC1, PubMed:24947615. May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1, PubMed:23274085. May also mediate TP53 inhibition of TORC1 signaling upon genotoxic stress, PubMed:18692468. Has an alkylhydroperoxide reductase activity born by the N-terminal domain of the protein, PubMed:26612684. Was originally reported to contribute to oxidative stress resistance by reducing PRDX1, PubMed:15105503. However, this could not be confirmed, PubMed:19113821. {ECO:0000269|PubMed:15105503, ECO:0000269|PubMed:18692468, ECO:0000269|PubMed:19113821, ECO:0000269|PubMed:23274085, ECO:0000269|PubMed:24947615, ECO:0000269|PubMed:25263562, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:26449471, ECO:0000269|PubMed:26586190, ECO:0000269|PubMed:26612684}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:15105503}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P58004
Gene Ontology
(Biological Process)
Complete annatation
autophagy [GO:0006914];
cellular oxidant detoxification [GO:0098869];
cellular response to amino acid stimulus [GO:0071230];
cellular response to leucine [GO:0071233];
cellular response to oxidative stress [GO:0034599];
DNA damage response, signal transduction by p53 class mediator [GO:0030330];
fatty acid beta-oxidation [GO:0006635];
glucose import [GO:0046323];
mitochondrial DNA metabolic process [GO:0032042];
negative regulation of cell growth [GO:0030308];
negative regulation of TORC1 signaling [GO:1904262];
negative regulation of translation in response to endoplasmic reticulum stress [GO:1902010];
positive regulation of macroautophagy [GO:0016239];
positive regulation of protein localization to nucleus [GO:1900182];
positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress [GO:0036091];
protein kinase B signaling [GO:0043491];
reactive oxygen species metabolic process [GO:0072593];
regulation of cAMP-dependent protein kinase activity [GO:2000479];
regulation of gluconeogenesis involved in cellular glucose homeostasis [GO:0090526];
regulation of protein phosphorylation [GO:0001932];
regulation of response to reactive oxygen species [GO:1901031];
response to glucose [GO:0009749];
response to insulin [GO:0032868];
triglyceride homeostasis [GO:0070328]
Gene Ontology
(Molecular Function)
Complete annatation
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
mitochondrion [GO:0005739];
nucleus [GO:0005634]
Protein-protein interaction123724
Phylogenetic treeP58004
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. CD3-0.9213214776570990.005481961540867770.0156633411078595
AZA vs. DISU-0.1447874010347330.5739149567332420.954304256505839
AZA vs. IL7-0.2929810251336130.2740601443704370.999311006273513
AZA vs. SAHA-0.06251358095901120.8290171544602920.959284914894791
DISU vs. CD30.7647987615111350.03688161630422270.0845568130502945
DISU vs. IL7-0.1584810849984290.5712282706097460.862454130763347
DISU vs. SAHA0.08540341452353430.7766732576615050.937995245309443
DMSO vs. AZA-0.05364318241693290.7937006910085681
DMSO vs. CD30.8582665512374980.008024471897670860.0206224273521685
DMSO vs. DISU0.08993036963947880.7143533204510270.962685308322123
DMSO vs. IL7-0.2322115290432920.3256322765974930.801315988833943
DMSO vs. SAHA-0.01344198031915350.9587487868164150.990304995115509
HIV vs. Mock in Activation0.2618919595078880.6763300278849180.999983755607037
HIV vs. Mock in Latency0.01962520669239520.9064230906783570.999834320637052
IL7 vs. CD30.6321766734264050.05219764984215870.113827427093585
SAHA vs. CD30.8365236550353180.01955812993627290.0452264873622269
SAHA vs. IL70.2289042847833340.4716974724991810.705736917495693
(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 0.0192757 0.926446
(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
1.086 0.952 1.231 0.781 0.951
(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
5CUF X-ray 3.5Å A/B/C/D/E=1-480.
5DJ4 X-ray 2.7Å A/B/C/D/E=1-480.
5T0N X-ray 3.0Å A/B/C/D/E=1-480.

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
hsa04115 p53 signaling pathway - Homo sapiens (human)
hsa04150 mTOR signaling pathway - Homo sapiens (human)
hsa04211 Longevity regulating pathway - Homo sapiens (human)