Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001127
UniProt IDP24522
Primary gene name(s)GADD45A
Synonym gene name(s)DDIT1, GADD45
Protein nameGrowth arrest and DNA damage-inducible protein GADD45 alpha
Protein functionIn T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity, By similarity. Might affect PCNA interaction with some CDK, cell division protein kinase complexes; stimulates DNA excision repair in vitro and inhibits entry of cells into S phase. {ECO:0000250}.
Subcellular locationNucleus {ECO:0000269|PubMed:7973727}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P24522
Gene Ontology
(Biological Process)
Complete annatation
activation of MAPKKK activity [GO:0000185];
apoptotic process [GO:0006915];
cell cycle arrest [GO:0007050];
cellular response to ionizing radiation [GO:0071479];
cellular response to mechanical stimulus [GO:0071260];
centrosome cycle [GO:0007098];
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest [GO:0006977];
DNA repair [GO:0006281];
mitotic cell cycle arrest [GO:0071850];
negative regulation of protein kinase activity [GO:0006469];
positive regulation of apoptotic process [GO:0043065];
positive regulation of JNK cascade [GO:0046330];
positive regulation of p38MAPK cascade [GO:1900745];
positive regulation of reactive oxygen species metabolic process [GO:2000379];
regulation of cyclin-dependent protein serine/threonine kinase activity [GO:0000079];
signal transduction in response to DNA damage [GO:0042770]
Gene Ontology
(Molecular Function)
Complete annatation
core promoter binding [GO:0001047]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction108014
Phylogenetic treeP24522
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. CD32.102802308195453.47689613744429e-062.39505386579343e-05
AZA vs. DISU-0.1434756736849510.5763633589430150.954304256505839
AZA vs. IL7-0.3133973427434420.1542024374430240.922020841096286
AZA vs. SAHA-0.4503693427011340.07072734376765030.328448545888343
DISU vs. CD3-2.260207694135392.21262892385887e-061.94592581086632e-05
DISU vs. IL7-0.1797319713993660.4823398783740880.815622396689779
DISU vs. SAHA-0.3043713337518940.3027357063737830.687231485277795
DMSO vs. AZA-0.5513991284234790.02315784698447451
DMSO vs. CD3-2.65962300686941.40935277115339e-071.203622420489e-06
DMSO vs. DISU-0.4081097294499380.1333762256891260.623975061846561
DMSO vs. IL70.2443617145998890.3862016525351250.837514642401658
DMSO vs. SAHA0.09295993302664630.7111121047304440.913124044876559
HIV vs. Mock in Activation0.6875859904149070.3768741414522780.999983755607037
HIV vs. Mock in Latency-0.1829899611839780.5138993582275280.999834320637052
IL7 vs. CD3-2.411698639618387.48289349372655e-077.52432645970249e-06
SAHA vs. CD3-2.577340889013032.23947348443332e-082.76403484114743e-07
SAHA vs. IL7-0.1391335398009830.5760981350015860.780944540199093
(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
0.3885 0.03673

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 0.955 7.95E-09 4.94E-07
Infected vs. Bystander 0.867 4.47E-08 1.31E-06
(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 0.911908 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
203725_at 2.84 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
2KG4 NMR - A=1-165.

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

HIV Partner Interaction Type PubMed
Vpr upregulates 15650754

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04110 Cell cycle - Homo sapiens (human)
hsa04115 p53 signaling pathway - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)