Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002170
UniProt IDO60346
Primary gene name(s)PHLPP1
Synonym gene name(s)KIAA0606, PHLPP, PLEKHE1, SCOP
Protein namePH domain leucine-rich repeat-containing protein phosphatase 1
Protein functionProtein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA, PubMed:15808505, PubMed:17386267, PubMed:18162466. Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons, By similarity. Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation, PubMed:18162466. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis, PubMed:20513427. Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation, PubMed:21986499. Inhibits cancer cell proliferation and may act as a tumor suppressor, PubMed:19079341. Dephosphorylates RAF1 inhibiting its kinase activity, PubMed:24530606. May act as a negative regulator of K-Ras signaling in membrane rafts, By similarity. Involved in the hippocampus-dependent long-term memory formation, By similarity. Involved in circadian control by regulating the consolidation of circadian periodicity after resetting, By similarity. Involved in development and function of regulatory T-cells, By similarity. {ECO:0000250|UniProtKB:Q8CHE4, ECO:0000250|UniProtKB:Q9WTR8, ECO:0000269|PubMed:15808505, ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19079341, ECO:0000269|PubMed:21986499, ECO:0000269|PubMed:24530606}.
Subcellular locationCytoplasm. Membrane;
Peripheral membrane protein. Nucleus. Note=In colorectal cancer tissue, expression is concentrated at the lateral membrane of epithelial cells.;
SUBCELLULAR LOCATION: Isoform 2: Cell membrane {ECO:0000269|PubMed:21804599}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O60346
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
entrainment of circadian clock [GO:0009649];
negative regulation of protein kinase B signaling [GO:0051898];
regulation of apoptotic process [GO:0042981];
regulation of JNK cascade [GO:0046328];
regulation of MAPK cascade [GO:0043408];
regulation of p38MAPK cascade [GO:1900744];
regulation of T cell anergy [GO:0002667]
Gene Ontology
(Molecular Function)
Complete annatation
metal ion binding [GO:0046872];
phosphoprotein phosphatase activity [GO:0004721]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
nucleus [GO:0005634];
plasma membrane [GO:0005886]
Protein-protein interaction116843
Phylogenetic treeO60346
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. CD32.121784952798017.96602117603129e-101.17594388996223e-08
AZA vs. DISU0.6744231635525270.01380978257742880.285553720949468
AZA vs. IL7-0.2192724981814250.2877362004253130.999311006273513
AZA vs. SAHA1.435236237600261.2806934712728e-060.000117714471865647
DISU vs. CD3-1.461344790123798.24479614095486e-050.000478007911649052
DISU vs. IL7-0.9023269428277010.003590701589430530.0611112905556524
DISU vs. SAHA0.7647361216558280.04873720196458190.275513267369922
DMSO vs. AZA0.01358597476599890.9406677905911361
DMSO vs. CD3-2.122298714829492.90183987949888e-104.17937072511e-09
DMSO vs. DISU-0.6629927809767540.0181044887975510.276148427306775
DMSO vs. IL7-0.2254818088717540.267912291878770.767539423873874
DMSO vs. SAHA1.416761469831932.70732004470364e-060.000191558781191214
HIV vs. Mock in Activation0.1503584031788170.8121304479006650.999983755607037
HIV vs. Mock in Latency0.001965025082990350.9909649082068130.999834320637052
IL7 vs. CD3-2.333810332621576.75537403793669e-121.72446348608961e-10
SAHA vs. CD3-0.7090615922071460.07756741648039010.142120482232156
SAHA vs. IL71.652679030426821.30673905596179e-065.70950276219364e-05
(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 0.0386888 0.853295
(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

not found

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
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)