Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002368
UniProt IDP60484
Primary gene name(s)PTEN
Synonym gene name(s)MMAC1, TEP1
Protein namePhosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
Protein functionTumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5P3 > PtdIns(3,4P2 > PtdIns3P > Ins(1,3,4,5P4, PubMed:26504226. The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with AIP1 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement. {ECO:0000269|PubMed:26504226}.; FUNCTION: Isoform alpha: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1.
Subcellular locationCytoplasm. Nucleus. Nucleus, PML body. Note=Monoubiquitinated form is nuclear. Nonubiquitinated form is cytoplasmic. Colocalized with PML and USP7 in PML nuclear bodies. XIAP/BIRC4 promotes its nuclear localization.;
SUBCELLULAR LOCATION: Isoform alpha: Secreted {ECO:0000269|PubMed:23744781, ECO:0000269|PubMed:24768297}. Note=May be secreted via a classical signal peptide and reenter into cells with the help of a poly-Arg motif.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P60484
Gene Ontology
(Biological Process)
Complete annatation
adult behavior [GO:0030534];
aging [GO:0007568];
angiogenesis [GO:0001525];
apoptotic process [GO:0006915];
brain morphogenesis [GO:0048854];
canonical Wnt signaling pathway [GO:0060070];
cardiac muscle tissue development [GO:0048738];
cell migration [GO:0016477];
cell proliferation [GO:0008283];
cellular response to hypoxia [GO:0071456];
central nervous system development [GO:0007417];
central nervous system myelin maintenance [GO:0032286];
central nervous system neuron axonogenesis [GO:0021955];
dendritic spine morphogenesis [GO:0060997];
dentate gyrus development [GO:0021542];
endothelial cell migration [GO:0043542];
forebrain morphogenesis [GO:0048853];
heart development [GO:0007507];
inositol phosphate dephosphorylation [GO:0046855];
inositol phosphate metabolic process [GO:0043647];
learning or memory [GO:0007611];
locomotor rhythm [GO:0045475];
locomotory behavior [GO:0007626];
long term synaptic depression [GO:0060292];
long-term synaptic potentiation [GO:0060291];
male mating behavior [GO:0060179];
maternal behavior [GO:0042711];
memory [GO:0007613];
multicellular organismal response to stress [GO:0033555];
negative regulation of apoptotic process [GO:0043066];
negative regulation of axonogenesis [GO:0050771];
negative regulation of axon regeneration [GO:0048681];
negative regulation of cardiac muscle cell proliferation [GO:0060044];
negative regulation of cell aging [GO:0090344];
negative regulation of cell migration [GO:0030336];
negative regulation of cell proliferation [GO:0008285];
negative regulation of cell size [GO:0045792];
negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle [GO:0031658];
negative regulation of dendritic spine morphogenesis [GO:0061002];
negative regulation of epithelial cell proliferation [GO:0050680];
negative regulation of ERK1 and ERK2 cascade [GO:0070373];
negative regulation of excitatory postsynaptic potential [GO:0090394];
negative regulation of focal adhesion assembly [GO:0051895];
negative regulation of G1/S transition of mitotic cell cycle [GO:2000134];
negative regulation of myelination [GO:0031642];
negative regulation of organ growth [GO:0046621];
negative regulation of phagocytosis [GO:0050765];
negative regulation of phosphatidylinositol 3-kinase signaling [GO:0014067];
negative regulation of protein kinase B signaling [GO:0051898];
negative regulation of protein phosphorylation [GO:0001933];
negative regulation of ribosome biogenesis [GO:0090071];
negative regulation of synaptic vesicle clustering [GO:2000808];
neuron-neuron synaptic transmission [GO:0007270];
phosphatidylinositol biosynthetic process [GO:0006661];
phosphatidylinositol dephosphorylation [GO:0046856];
phosphatidylinositol-mediated signaling [GO:0048015];
platelet-derived growth factor receptor signaling pathway [GO:0048008];
positive regulation of cell proliferation [GO:0008284];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of excitatory postsynaptic potential [GO:2000463];
positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:2000060];
positive regulation of sequence-specific DNA binding transcription factor activity [GO:0051091];
positive regulation of TRAIL-activated apoptotic signaling pathway [GO:1903984];
positive regulation of ubiquitin protein ligase activity [GO:1904668];
postsynaptic density assembly [GO:0097107];
prepulse inhibition [GO:0060134];
presynaptic membrane assembly [GO:0097105];
prostate gland growth [GO:0060736];
protein dephosphorylation [GO:0006470];
protein kinase B signaling [GO:0043491];
protein stabilization [GO:0050821];
regulation of B cell apoptotic process [GO:0002902];
regulation of cellular component size [GO:0032535];
regulation of cyclin-dependent protein serine/threonine kinase activity [GO:0000079];
regulation of myeloid cell apoptotic process [GO:0033032];
regulation of neuron projection development [GO:0010975];
regulation of protein stability [GO:0031647];
regulation of synaptic transmission, GABAergic [GO:0032228];
response to arsenic-containing substance [GO:0046685];
response to ATP [GO:0033198];
response to drug [GO:0042493];
response to estradiol [GO:0032355];
response to ethanol [GO:0045471];
response to glucose [GO:0009749];
response to nutrient [GO:0007584];
response to zinc ion [GO:0010043];
rhythmic synaptic transmission [GO:0060024];
social behavior [GO:0035176];
synapse assembly [GO:0007416];
synapse maturation [GO:0060074];
T cell receptor signaling pathway [GO:0050852]
Gene Ontology
(Molecular Function)
Complete annatation
anaphase-promoting complex binding [GO:0010997];
enzyme binding [GO:0019899];
identical protein binding [GO:0042802];
inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity [GO:0051717];
lipid binding [GO:0008289];
magnesium ion binding [GO:0000287];
PDZ domain binding [GO:0030165];
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity [GO:0016314];
phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity [GO:0051800];
phosphatidylinositol-3-phosphatase activity [GO:0004438];
phosphoprotein phosphatase activity [GO:0004721];
protein serine/threonine phosphatase activity [GO:0004722];
protein tyrosine/serine/threonine phosphatase activity [GO:0008138];
protein tyrosine phosphatase activity [GO:0004725]
Gene Ontology
(Cellular Component)
Complete annatation
apical plasma membrane [GO:0016324];
cell projection [GO:0042995];
cytoplasm [GO:0005737];
cytoplasmic side of plasma membrane [GO:0009898];
cytosol [GO:0005829];
dendritic spine [GO:0043197];
extracellular region [GO:0005576];
mitochondrion [GO:0005739];
myelin sheath adaxonal region [GO:0035749];
neuron projection [GO:0043005];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
PML body [GO:0016605];
postsynaptic membrane [GO:0045211];
Schmidt-Lanterman incisure [GO:0043220]
Protein-protein interaction111700
Phylogenetic treeP60484
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. CD3-0.6484884169701310.04823850298891270.0968626055221014
AZA vs. DISU0.0422492690609650.867805027977660.991211477030548
AZA vs. IL70.00864661441959070.9657663027930280.999311006273513
AZA vs. SAHA0.1944246858287150.42482390615950.777343619730284
DISU vs. CD30.6785665537991330.06344024055399060.130731125920828
DISU vs. IL7-0.0421330517666480.8672898655794750.974537471944736
DISU vs. SAHA0.1520320677752580.6039451756664950.874985752839509
DMSO vs. AZA-0.2098992223925230.2094213687904411
DMSO vs. CD30.4273608437426730.1815518142243250.277013151737762
DMSO vs. DISU-0.2539202148271110.3002390420027550.807887568985919
DMSO vs. IL70.2257445414533110.208902850963990.717686982288547
DMSO vs. SAHA0.3961823180792790.09280956090393990.35773219754048
HIV vs. Mock in Activation0.05468122986475970.9299101802953750.999983755607037
HIV vs. Mock in Latency0.01142619248407270.9446539834896430.999834320637052
IL7 vs. CD30.6665397440978360.03868280556205750.0891265558295464
SAHA vs. CD30.8164557586997470.02148405319422190.0489366205618083
SAHA vs. IL70.1809820505883570.4572632364198830.694277399858311
(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) 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 -0.23391 0.0857582
(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
1D5R X-ray 2.1Å A=8-353.
2KYL NMR - B=391-403.
4O1V X-ray 2.0Å B=354-368.
5BUG X-ray 2.4Å A/B/C/D=14-351.
5BZX X-ray 2.5Å A/B/C/D=14-351.
5BZZ X-ray 2.2Å A/B/C/D=14-351.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 cooperates with 21234828
matrix induces phosphorylation of 21423810
Nef interacts with 25104021
Tat enhanced by 12077252
Tat induces phosphorylation of 23301033
Tat upregulates 19050264
Tat downregulates 17157319
HIV-1 virus replication enhanced by expression of human gene 19460752
matrix activates 21423810

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00562 Inositol phosphate metabolism - Homo sapiens (human)
hsa01521 EGFR tyrosine kinase inhibitor resistance - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04070 Phosphatidylinositol signaling system - Homo sapiens (human)
hsa04071 Sphingolipid signaling pathway - Homo sapiens (human)
hsa04115 p53 signaling pathway - Homo sapiens (human)
hsa04150 mTOR signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05213 Endometrial cancer - Homo sapiens (human)
hsa05214 Glioma - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05218 Melanoma - Homo sapiens (human)
hsa05222 Small cell lung cancer - Homo sapiens (human)
hsa05224 Breast cancer - Homo sapiens (human)
hsa05230 Central carbon metabolism in cancer - Homo sapiens (human)