Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002293
UniProt IDO75807
Primary gene name(s)PPP1R15A
Synonym gene name(s)GADD34
Protein nameProtein phosphatase 1 regulatory subunit 15A
Protein functionRecruits the serine/threonine-protein phosphatase PP1 to dephosphorylate the translation initiation factor eIF-2A/EIF2S1, thereby reversing the shut-off of protein synthesis initiated by stress-inducible kinases and facilitating recovery of cells from stress. Down-regulates the TGF-beta signaling pathway by promoting dephosphorylation of TGFB1 by PP1. May promote apoptosis by inducing TP53 phosphorylation on 'Ser-15'. {ECO:0000269|PubMed:11564868, ECO:0000269|PubMed:12556489, ECO:0000269|PubMed:14635196, ECO:0000269|PubMed:14718519, ECO:0000269|PubMed:8139541}.
Subcellular locationEndoplasmic reticulum membrane;
Peripheral membrane protein;
Cytoplasmic side {ECO:0000269|PubMed:12556489, ECO:0000269|PubMed:21518769}. Mitochondrion outer membrane;
Peripheral membrane protein;
Cytoplasmic side {ECO:0000269|PubMed:21518769}. Note=Associates with membranes via an N-terminal amphipathic intramembrane region. {ECO:0000269|PubMed:21518769}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O75807
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
cell cycle arrest [GO:0007050];
cellular response to DNA damage stimulus [GO:0006974];
endoplasmic reticulum unfolded protein response [GO:0030968];
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress [GO:0070059];
negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation [GO:1903912];
negative regulation of PERK-mediated unfolded protein response [GO:1903898];
negative regulation of phosphoprotein phosphatase activity [GO:0032515];
negative regulation of protein dephosphorylation [GO:0035308];
negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress [GO:1990441];
peptidyl-serine dephosphorylation [GO:0070262];
positive regulation of endoplasmic reticulum stress-induced eIF2 alpha dephosphorylation [GO:1903917];
positive regulation of peptidyl-serine dephosphorylation [GO:1902310];
positive regulation of peptidyl-serine phosphorylation [GO:0033138];
positive regulation of phosphoprotein phosphatase activity [GO:0032516];
positive regulation of transcription from RNA polymerase I promoter [GO:0045943];
positive regulation of translational initiation in response to stress [GO:0032058];
protein localization to endoplasmic reticulum [GO:0070972];
regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation [GO:0060734];
regulation of translational initiation by eIF2 alpha dephosphorylation [GO:0036496];
response to endoplasmic reticulum stress [GO:0034976]
Gene Ontology
(Molecular Function)
Complete annatation
protein kinase binding [GO:0019901];
protein phosphatase 1 binding [GO:0008157];
protein phosphatase type 1 activator activity [GO:0071862];
protein phosphatase type 1 regulator activity [GO:0008599]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endoplasmic reticulum [GO:0005783];
endoplasmic reticulum membrane [GO:0005789];
Golgi apparatus [GO:0005794];
membrane [GO:0016020];
mitochondrial outer membrane [GO:0005741];
mitochondrion [GO:0005739];
protein phosphatase type 1 complex [GO:0000164]
Protein-protein interaction117172
Phylogenetic treeO75807
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD30.4411214605231790.1822319640068070.283769001085918
AZA vs. DISU1.264947766724068.66173403446524e-070.000373048510958654
AZA vs. IL7-0.417693519626060.03168157147430140.555184885505601
AZA vs. SAHA0.03479941906967520.8871861404000550.975652039918686
DISU vs. CD30.8087007093564480.02746257988211950.0666405230429926
DISU vs. IL7-1.691330836060216.82740530777437e-113.5490736211965e-08
DISU vs. SAHA-1.227468119861823.35678546351525e-050.00167516932849796
DMSO vs. AZA-0.09999492129863680.5549844708451311
DMSO vs. CD3-0.5539504960809220.08708526908713440.152675384475466
DMSO vs. DISU-1.36722800468783.83029121753253e-082.40510369367564e-05
DMSO vs. IL7-0.310100170693710.08810113108332950.553801387267045
DMSO vs. SAHA0.1287640566520060.5873170524873710.858723541241692
HIV vs. Mock in Activation0.3457986965057770.5796105532696540.999983755607037
HIV vs. Mock in Latency-0.3010013282175470.3081152313685550.999834320637052
IL7 vs. CD3-0.8518784072052750.009318069126043160.0281296326731121
SAHA vs. CD3-0.4305983197719540.2249027391786570.330887853111623
SAHA vs. IL70.4490517359032080.067991597283080.225105499109411
(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
0.4212 0.04998

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 0.581155 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
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
4XPN X-ray 2.2Å B/D=552-591.

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
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)
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