Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000768
UniProt IDQ9NX09
Primary gene name(s)DDIT4
Synonym gene name(s)REDD1, RTP801
Protein nameDNA damage-inducible transcript 4 protein
Protein functionRegulates cell growth, proliferation and survival via inhibition of the activity of the mammalian target of rapamycin complex 1, mTORC1. Inhibition of mTORC1 is mediated by a pathway that involves DDIT4/REDD1, AKT1, the TSC1-TSC2 complex and the GTPase RHEB. Plays an important role in responses to cellular energy levels and cellular stress, including responses to hypoxia and DNA damage. Regulates p53/TP53-mediated apoptosis in response to DNA damage via its effect on mTORC1 activity. Its role in the response to hypoxia depends on the cell type; it mediates mTORC1 inhibition in fibroblasts and thymocytes, but not in hepatocytes, By similarity. Required for mTORC1-mediated defense against viral protein synthesis and virus replication, By similarity. Inhibits neuronal differentiation and neurite outgrowth mediated by NGF via its effect on mTORC1 activity. Required for normal neuron migration during embryonic brain development. Plays a role in neuronal cell death. {ECO:0000250, ECO:0000269|PubMed:15545625, ECO:0000269|PubMed:15632201, ECO:0000269|PubMed:15988001, ECO:0000269|PubMed:17005863, ECO:0000269|PubMed:17379067, ECO:0000269|PubMed:19557001, ECO:0000269|PubMed:20166753, ECO:0000269|PubMed:21460850}.
Subcellular locationMitochondrion {ECO:0000250}. Cytoplasm, cytosol {ECO:0000269|PubMed:12453409}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9NX09
Gene Ontology
(Biological Process)
Complete annatation
brain development [GO:0007420];
cell proliferation [GO:0008283];
cellular response to dexamethasone stimulus [GO:0071549];
defense response to virus [GO:0051607];
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator [GO:0042771];
negative regulation of glycolytic process [GO:0045820];
negative regulation of intracellular signal transduction [GO:1902532];
negative regulation of peptidyl-serine phosphorylation [GO:0033137];
negative regulation of peptidyl-threonine phosphorylation [GO:0010801];
negative regulation of TOR signaling [GO:0032007];
neuron differentiation [GO:0030182];
neuron migration [GO:0001764];
neurotrophin TRK receptor signaling pathway [GO:0048011];
positive regulation of neuron death [GO:1901216];
protein complex disassembly [GO:0043241];
reactive oxygen species metabolic process [GO:0072593];
response to hypoxia [GO:0001666]
Gene Ontology
(Molecular Function)
Complete annatation
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
intracellular [GO:0005622];
mitochondrion [GO:0005739]
Protein-protein interaction120028
Phylogenetic treeQ9NX09
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: HCV
      Viral life cycle: translation
      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. CD3-1.156526059312230.0005028728605737110.00200034303366771
AZA vs. DISU-0.79845134285080.006705171104354650.208399482942354
AZA vs. IL70.04568837301342580.8242157941838830.999311006273513
AZA vs. SAHA0.0482465103111210.8435305203372060.962765687434222
DISU vs. CD30.3468703629524690.3463393294830480.479801401767068
DISU vs. IL70.8336296771219850.004218881213219120.0674985099133832
DISU vs. SAHA0.8492135855969310.003967155967367520.0545820724662214
DMSO vs. AZA0.02614188889822310.9002207325897241
DMSO vs. CD31.174701221988810.0002989773835658790.00118591213360189
DMSO vs. DISU0.8234885810873820.004965342813155190.151473109704957
DMSO vs. IL70.02636419371330030.8975020167241120.978119473930297
DMSO vs. SAHA0.01594874611391680.9461443804578750.987406241330154
HIV vs. Mock in Activation0.6024512070977570.3358760414339220.999983755607037
HIV vs. Mock in Latency0.006960576282112160.9756394300100320.999834320637052
IL7 vs. CD31.206616136536780.0002152592916230270.00113866908953245
SAHA vs. CD31.181607279198240.001013128057987370.0036246021903459
SAHA vs. IL70.001019841227886430.9966757793507260.998449463725995
(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
0.8094 0.01218

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 1.206 4.34E-11 8.39E-09
Infected vs. Bystander 1.169 8.22E-11 7.47E-09
(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 1.1163 0.000305467
(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
202887_s_at 1.5 No downregulated in CD8+ cells

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
3LQ9 X-ray 2.0Å A/B=89-226.

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
hsa04150 mTOR signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)