Browse PTEN

Summary
SymbolPTEN
Namephosphatase and tensin homolog
Aliases MMAC1; PTEN1; mutated in multiple advanced cancers 1; BZS; MHAM; CWS1; DEC; GLM2; MMAC11; MMAC1 phosphatase ......
Chromosomal Location10q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm Nucleus Nucleus, PML body Note=Monoubiquitinated form is nuclear. Nonubiquitinated form is cytoplasmic. Colocalized with PML and USP7 in PML nuclear bodies (PubMed:18716620). XIAP/BIRC4 promotes its nuclear localization (PubMed:19473982). ; SUBCELLULAR LOCATION: Isoform alpha: Secreted Note=May be secreted via a classical signal peptide and reenter into cells with the help of a poly-Arg motif.
Domain PF00782 Dual specificity phosphatase
PF10409 C2 domain of PTEN tumour-suppressor protein
Function

Tumor 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(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4 (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. ; 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.

> Gene Ontology
 
Biological Process GO:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0000082 G1/S transition of mitotic cell cycle
GO:0001525 angiogenesis
GO:0001655 urogenital system development
GO:0001666 response to hypoxia
GO:0001667 ameboidal-type cell migration
GO:0001783 B cell apoptotic process
GO:0001933 negative regulation of protein phosphorylation
GO:0001952 regulation of cell-matrix adhesion
GO:0001953 negative regulation of cell-matrix adhesion
GO:0001964 startle response
GO:0002429 immune response-activating cell surface receptor signaling pathway
GO:0002757 immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0002768 immune response-regulating cell surface receptor signaling pathway
GO:0002902 regulation of B cell apoptotic process
GO:0006066 alcohol metabolic process
GO:0006469 negative regulation of protein kinase activity
GO:0006470 protein dephosphorylation
GO:0006644 phospholipid metabolic process
GO:0006650 glycerophospholipid metabolic process
GO:0006661 phosphatidylinositol biosynthetic process
GO:0006909 phagocytosis
GO:0007009 plasma membrane organization
GO:0007044 cell-substrate junction assembly
GO:0007045 cell-substrate adherens junction assembly
GO:0007160 cell-matrix adhesion
GO:0007162 negative regulation of cell adhesion
GO:0007270 neuron-neuron synaptic transmission
GO:0007272 ensheathment of neurons
GO:0007346 regulation of mitotic cell cycle
GO:0007409 axonogenesis
GO:0007416 synapse assembly
GO:0007507 heart development
GO:0007517 muscle organ development
GO:0007568 aging
GO:0007569 cell aging
GO:0007584 response to nutrient
GO:0007611 learning or memory
GO:0007613 memory
GO:0007617 mating behavior
GO:0007618 mating
GO:0007622 rhythmic behavior
GO:0007623 circadian rhythm
GO:0007626 locomotory behavior
GO:0008361 regulation of cell size
GO:0008366 axon ensheathment
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors
GO:0008654 phospholipid biosynthetic process
GO:0009743 response to carbohydrate
GO:0009746 response to hexose
GO:0009749 response to glucose
GO:0009894 regulation of catabolic process
GO:0009896 positive regulation of catabolic process
GO:0009991 response to extracellular stimulus
GO:0010001 glial cell differentiation
GO:0010035 response to inorganic substance
GO:0010038 response to metal ion
GO:0010043 response to zinc ion
GO:0010631 epithelial cell migration
GO:0010721 negative regulation of cell development
GO:0010769 regulation of cell morphogenesis involved in differentiation
GO:0010771 negative regulation of cell morphogenesis involved in differentiation
GO:0010810 regulation of cell-substrate adhesion
GO:0010812 negative regulation of cell-substrate adhesion
GO:0010948 negative regulation of cell cycle process
GO:0010975 regulation of neuron projection development
GO:0010977 negative regulation of neuron projection development
GO:0014003 oligodendrocyte development
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0014066 regulation of phosphatidylinositol 3-kinase signaling
GO:0014067 negative regulation of phosphatidylinositol 3-kinase signaling
GO:0014074 response to purine-containing compound
GO:0014706 striated muscle tissue development
GO:0014855 striated muscle cell proliferation
GO:0016055 Wnt signaling pathway
GO:0016202 regulation of striated muscle tissue development
GO:0016311 dephosphorylation
GO:0016358 dendrite development
GO:0019098 reproductive behavior
GO:0019751 polyol metabolic process
GO:0021537 telencephalon development
GO:0021542 dentate gyrus development
GO:0021543 pallium development
GO:0021700 developmental maturation
GO:0021761 limbic system development
GO:0021766 hippocampus development
GO:0021782 glial cell development
GO:0021953 central nervous system neuron differentiation
GO:0021954 central nervous system neuron development
GO:0021955 central nervous system neuron axonogenesis
GO:0022010 central nervous system myelination
GO:0022604 regulation of cell morphogenesis
GO:0022613 ribonucleoprotein complex biogenesis
GO:0030100 regulation of endocytosis
GO:0030258 lipid modification
GO:0030336 negative regulation of cell migration
GO:0030534 adult behavior
GO:0030850 prostate gland development
GO:0030900 forebrain development
GO:0031099 regeneration
GO:0031102 neuron projection regeneration
GO:0031103 axon regeneration
GO:0031329 regulation of cellular catabolic process
GO:0031331 positive regulation of cellular catabolic process
GO:0031345 negative regulation of cell projection organization
GO:0031396 regulation of protein ubiquitination
GO:0031398 positive regulation of protein ubiquitination
GO:0031589 cell-substrate adhesion
GO:0031641 regulation of myelination
GO:0031642 negative regulation of myelination
GO:0031644 regulation of neurological system process
GO:0031645 negative regulation of neurological system process
GO:0031647 regulation of protein stability
GO:0031657 regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
GO:0031658 negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
GO:0031667 response to nutrient levels
GO:0032102 negative regulation of response to external stimulus
GO:0032228 regulation of synaptic transmission, GABAergic
GO:0032286 central nervous system myelin maintenance
GO:0032291 axon ensheathment in central nervous system
GO:0032355 response to estradiol
GO:0032535 regulation of cellular component size
GO:0033002 muscle cell proliferation
GO:0033028 myeloid cell apoptotic process
GO:0033032 regulation of myeloid cell apoptotic process
GO:0033198 response to ATP
GO:0033555 multicellular organismal response to stress
GO:0033673 negative regulation of kinase activity
GO:0034284 response to monosaccharide
GO:0034329 cell junction assembly
GO:0034330 cell junction organization
GO:0034332 adherens junction organization
GO:0034333 adherens junction assembly
GO:0035176 social behavior
GO:0035265 organ growth
GO:0035335 peptidyl-tyrosine dephosphorylation
GO:0036293 response to decreased oxygen levels
GO:0036294 cellular response to decreased oxygen levels
GO:0036462 TRAIL-activated apoptotic signaling pathway
GO:0040013 negative regulation of locomotion
GO:0042063 gliogenesis
GO:0042176 regulation of protein catabolic process
GO:0042254 ribosome biogenesis
GO:0042326 negative regulation of phosphorylation
GO:0042391 regulation of membrane potential
GO:0042493 response to drug
GO:0042552 myelination
GO:0042711 maternal behavior
GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0043217 myelin maintenance
GO:0043409 negative regulation of MAPK cascade
GO:0043410 positive regulation of MAPK cascade
GO:0043491 protein kinase B signaling
GO:0043542 endothelial cell migration
GO:0043647 inositol phosphate metabolic process
GO:0044057 regulation of system process
GO:0044091 membrane biogenesis
GO:0044262 cellular carbohydrate metabolic process
GO:0044282 small molecule catabolic process
GO:0044708 single-organism behavior
GO:0044723 single-organism carbohydrate metabolic process
GO:0044770 cell cycle phase transition
GO:0044772 mitotic cell cycle phase transition
GO:0044843 cell cycle G1/S phase transition
GO:0045017 glycerolipid biosynthetic process
GO:0045216 cell-cell junction organization
GO:0045471 response to ethanol
GO:0045475 locomotor rhythm
GO:0045665 negative regulation of neuron differentiation
GO:0045732 positive regulation of protein catabolic process
GO:0045736 negative regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0045786 negative regulation of cell cycle
GO:0045792 negative regulation of cell size
GO:0045806 negative regulation of endocytosis
GO:0045843 negative regulation of striated muscle tissue development
GO:0045862 positive regulation of proteolysis
GO:0045926 negative regulation of growth
GO:0045930 negative regulation of mitotic cell cycle
GO:0046164 alcohol catabolic process
GO:0046174 polyol catabolic process
GO:0046434 organophosphate catabolic process
GO:0046474 glycerophospholipid biosynthetic process
GO:0046486 glycerolipid metabolic process
GO:0046488 phosphatidylinositol metabolic process
GO:0046620 regulation of organ growth
GO:0046621 negative regulation of organ growth
GO:0046683 response to organophosphorus
GO:0046685 response to arsenic-containing substance
GO:0046838 phosphorylated carbohydrate dephosphorylation
GO:0046839 phospholipid dephosphorylation
GO:0046855 inositol phosphate dephosphorylation
GO:0046856 phosphatidylinositol dephosphorylation
GO:0048008 platelet-derived growth factor receptor signaling pathway
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048017 inositol lipid-mediated signaling
GO:0048041 focal adhesion assembly
GO:0048167 regulation of synaptic plasticity
GO:0048511 rhythmic process
GO:0048512 circadian behavior
GO:0048514 blood vessel morphogenesis
GO:0048608 reproductive structure development
GO:0048634 regulation of muscle organ development
GO:0048635 negative regulation of muscle organ development
GO:0048638 regulation of developmental growth
GO:0048640 negative regulation of developmental growth
GO:0048667 cell morphogenesis involved in neuron differentiation
GO:0048678 response to axon injury
GO:0048679 regulation of axon regeneration
GO:0048681 negative regulation of axon regeneration
GO:0048709 oligodendrocyte differentiation
GO:0048732 gland development
GO:0048738 cardiac muscle tissue development
GO:0048813 dendrite morphogenesis
GO:0048814 regulation of dendrite morphogenesis
GO:0048853 forebrain morphogenesis
GO:0048854 brain morphogenesis
GO:0050673 epithelial cell proliferation
GO:0050678 regulation of epithelial cell proliferation
GO:0050680 negative regulation of epithelial cell proliferation
GO:0050764 regulation of phagocytosis
GO:0050765 negative regulation of phagocytosis
GO:0050768 negative regulation of neurogenesis
GO:0050770 regulation of axonogenesis
GO:0050771 negative regulation of axonogenesis
GO:0050773 regulation of dendrite development
GO:0050774 negative regulation of dendrite morphogenesis
GO:0050804 modulation of synaptic transmission
GO:0050805 negative regulation of synaptic transmission
GO:0050806 positive regulation of synaptic transmission
GO:0050808 synapse organization
GO:0050821 protein stabilization
GO:0050851 antigen receptor-mediated signaling pathway
GO:0050852 T cell receptor signaling pathway
GO:0050890 cognition
GO:0050905 neuromuscular process
GO:0051051 negative regulation of transport
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051271 negative regulation of cellular component movement
GO:0051348 negative regulation of transferase activity
GO:0051438 regulation of ubiquitin-protein transferase activity
GO:0051443 positive regulation of ubiquitin-protein transferase activity
GO:0051640 organelle localization
GO:0051648 vesicle localization
GO:0051703 intraspecies interaction between organisms
GO:0051705 multi-organism behavior
GO:0051893 regulation of focal adhesion assembly
GO:0051895 negative regulation of focal adhesion assembly
GO:0051896 regulation of protein kinase B signaling
GO:0051898 negative regulation of protein kinase B signaling
GO:0051932 synaptic transmission, GABAergic
GO:0051961 negative regulation of nervous system development
GO:0055017 cardiac muscle tissue growth
GO:0055021 regulation of cardiac muscle tissue growth
GO:0055022 negative regulation of cardiac muscle tissue growth
GO:0055024 regulation of cardiac muscle tissue development
GO:0055026 negative regulation of cardiac muscle tissue development
GO:0060024 rhythmic synaptic transmission
GO:0060038 cardiac muscle cell proliferation
GO:0060043 regulation of cardiac muscle cell proliferation
GO:0060044 negative regulation of cardiac muscle cell proliferation
GO:0060070 canonical Wnt signaling pathway
GO:0060074 synapse maturation
GO:0060078 regulation of postsynaptic membrane potential
GO:0060079 excitatory postsynaptic potential
GO:0060134 prepulse inhibition
GO:0060179 male mating behavior
GO:0060291 long-term synaptic potentiation
GO:0060292 long term synaptic depression
GO:0060419 heart growth
GO:0060420 regulation of heart growth
GO:0060537 muscle tissue development
GO:0060627 regulation of vesicle-mediated transport
GO:0060736 prostate gland growth
GO:0060746 parental behavior
GO:0060996 dendritic spine development
GO:0060997 dendritic spine morphogenesis
GO:0060998 regulation of dendritic spine development
GO:0061000 negative regulation of dendritic spine development
GO:0061001 regulation of dendritic spine morphogenesis
GO:0061002 negative regulation of dendritic spine morphogenesis
GO:0061117 negative regulation of heart growth
GO:0061458 reproductive system development
GO:0061564 axon development
GO:0070227 lymphocyte apoptotic process
GO:0070228 regulation of lymphocyte apoptotic process
GO:0070371 ERK1 and ERK2 cascade
GO:0070372 regulation of ERK1 and ERK2 cascade
GO:0070373 negative regulation of ERK1 and ERK2 cascade
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070482 response to oxygen levels
GO:0070570 regulation of neuron projection regeneration
GO:0070571 negative regulation of neuron projection regeneration
GO:0071453 cellular response to oxygen levels
GO:0071456 cellular response to hypoxia
GO:0071545 inositol phosphate catabolic process
GO:0071709 membrane assembly
GO:0071887 leukocyte apoptotic process
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071901 negative regulation of protein serine/threonine kinase activity
GO:0090066 regulation of anatomical structure size
GO:0090069 regulation of ribosome biogenesis
GO:0090071 negative regulation of ribosome biogenesis
GO:0090109 regulation of cell-substrate junction assembly
GO:0090130 tissue migration
GO:0090132 epithelium migration
GO:0090342 regulation of cell aging
GO:0090344 negative regulation of cell aging
GO:0090394 negative regulation of excitatory postsynaptic potential
GO:0097061 dendritic spine organization
GO:0097090 presynaptic membrane organization
GO:0097091 synaptic vesicle clustering
GO:0097105 presynaptic membrane assembly
GO:0097106 postsynaptic density organization
GO:0097107 postsynaptic density assembly
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097305 response to alcohol
GO:0097479 synaptic vesicle localization
GO:0098815 modulation of excitatory postsynaptic potential
GO:0099054 presynapse assembly
GO:0099068 postsynapse assembly
GO:0099504 synaptic vesicle cycle
GO:0099565 chemical synaptic transmission, postsynaptic
GO:0198738 cell-cell signaling by wnt
GO:1901615 organic hydroxy compound metabolic process
GO:1901616 organic hydroxy compound catabolic process
GO:1901861 regulation of muscle tissue development
GO:1901862 negative regulation of muscle tissue development
GO:1901888 regulation of cell junction assembly
GO:1901889 negative regulation of cell junction assembly
GO:1901987 regulation of cell cycle phase transition
GO:1901988 negative regulation of cell cycle phase transition
GO:1901990 regulation of mitotic cell cycle phase transition
GO:1901991 negative regulation of mitotic cell cycle phase transition
GO:1902041 regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:1902043 positive regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:1902532 negative regulation of intracellular signal transduction
GO:1902806 regulation of cell cycle G1/S phase transition
GO:1902807 negative regulation of cell cycle G1/S phase transition
GO:1903034 regulation of response to wounding
GO:1903035 negative regulation of response to wounding
GO:1903050 regulation of proteolysis involved in cellular protein catabolic process
GO:1903052 positive regulation of proteolysis involved in cellular protein catabolic process
GO:1903121 regulation of TRAIL-activated apoptotic signaling pathway
GO:1903320 regulation of protein modification by small protein conjugation or removal
GO:1903322 positive regulation of protein modification by small protein conjugation or removal
GO:1903362 regulation of cellular protein catabolic process
GO:1903364 positive regulation of cellular protein catabolic process
GO:1903391 regulation of adherens junction organization
GO:1903392 negative regulation of adherens junction organization
GO:1903984 positive regulation of TRAIL-activated apoptotic signaling pathway
GO:1904029 regulation of cyclin-dependent protein kinase activity
GO:1904030 negative regulation of cyclin-dependent protein kinase activity
GO:1904666 regulation of ubiquitin protein ligase activity
GO:1904668 positive regulation of ubiquitin protein ligase activity
GO:1904861 excitatory synapse assembly
GO:1990267 response to transition metal nanoparticle
GO:2000045 regulation of G1/S transition of mitotic cell cycle
GO:2000058 regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2000060 positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2000106 regulation of leukocyte apoptotic process
GO:2000134 negative regulation of G1/S transition of mitotic cell cycle
GO:2000146 negative regulation of cell motility
GO:2000171 negative regulation of dendrite development
GO:2000463 positive regulation of excitatory postsynaptic potential
GO:2000807 regulation of synaptic vesicle clustering
GO:2000808 negative regulation of synaptic vesicle clustering
GO:2001233 regulation of apoptotic signaling pathway
GO:2001235 positive regulation of apoptotic signaling pathway
GO:2001236 regulation of extrinsic apoptotic signaling pathway
GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
Molecular Function GO:0000287 magnesium ion binding
GO:0004438 phosphatidylinositol-3-phosphatase activity
GO:0004721 phosphoprotein phosphatase activity
GO:0004722 protein serine/threonine phosphatase activity
GO:0004725 protein tyrosine phosphatase activity
GO:0005161 platelet-derived growth factor receptor binding
GO:0008138 protein tyrosine/serine/threonine phosphatase activity
GO:0010997 anaphase-promoting complex binding
GO:0016314 phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
GO:0016791 phosphatase activity
GO:0030165 PDZ domain binding
GO:0034593 phosphatidylinositol bisphosphate phosphatase activity
GO:0034594 phosphatidylinositol trisphosphate phosphatase activity
GO:0042578 phosphoric ester hydrolase activity
GO:0051717 inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
GO:0051800 phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
GO:0052743 inositol tetrakisphosphate phosphatase activity
GO:0052744 phosphatidylinositol monophosphate phosphatase activity
GO:0052745 inositol phosphate phosphatase activity
GO:0052866 phosphatidylinositol phosphate phosphatase activity
GO:0070851 growth factor receptor binding
Cellular Component GO:0009898 cytoplasmic side of plasma membrane
GO:0016324 apical plasma membrane
GO:0016604 nuclear body
GO:0016605 PML body
GO:0030425 dendrite
GO:0035749 myelin sheath adaxonal region
GO:0043197 dendritic spine
GO:0043209 myelin sheath
GO:0043218 compact myelin
GO:0043220 Schmidt-Lanterman incisure
GO:0044309 neuron spine
GO:0045177 apical part of cell
GO:0045211 postsynaptic membrane
GO:0097060 synaptic membrane
GO:0098552 side of membrane
GO:0098562 cytoplasmic side of membrane
GO:0098794 postsynapse
> KEGG and Reactome Pathway
 
KEGG hsa04068 FoxO signaling pathway
hsa04070 Phosphatidylinositol signaling system
hsa04071 Sphingolipid signaling pathway
hsa04115 p53 signaling pathway
hsa04140 Regulation of autophagy
hsa04150 mTOR signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04510 Focal adhesion
hsa00562 Inositol phosphate metabolism
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-5688426: Deubiquitination
R-HSA-202424: Downstream TCR signaling
R-HSA-186763: Downstream signal transduction
R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR)
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-180292: GAB1 signalosome
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-1483249: Inositol phosphate metabolism
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-392499: Metabolism of proteins
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-199418: Negative regulation of the PI3K/AKT network
R-HSA-5689896: Ovarian tumor domain proteases
R-HSA-1483255: PI Metabolism
R-HSA-198203: PI3K/AKT activation
R-HSA-1257604: PIP3 activates AKT signaling
R-HSA-1483257: Phospholipid metabolism
R-HSA-597592: Post-translational protein modification
R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-983705: Signaling by the B Cell Receptor (BCR)
R-HSA-166520: Signalling by NGF
R-HSA-1855204: Synthesis of IP3 and IP4 in the cytosol
R-HSA-1660499: Synthesis of PIPs at the plasma membrane
R-HSA-202403: TCR signaling
R-HSA-5628897: TP53 Regulates Metabolic Genes
R-HSA-3700989: Transcriptional Regulation by TP53
R-HSA-5689880: Ub-specific processing proteases
Summary
SymbolPTEN
Namephosphatase and tensin homolog
Aliases MMAC1; PTEN1; mutated in multiple advanced cancers 1; BZS; MHAM; CWS1; DEC; GLM2; MMAC11; MMAC1 phosphatase ......
Chromosomal Location10q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between PTEN and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between PTEN and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26645196MelanomaPromote immunity (infiltration)PTEN loss in tumor cells increased the expression of immunosuppressive cytokines, resulting in decreased T-cell infiltration in tumors, and inhibited autophagy, which decreased T cell-mediated cell death.
24662052Prostate carcinomaInhibit immunity (T cell function)Pten null prostate epithelium promotes localized myeloid-derived suppressor cell expansion and immune suppression during tumor initiation and progression. Using the Pten null murine prostate cancer model, we show an expansion of Gr-1(+) CD11b(+) myeloid-derived suppressor cells (MDSCs) occurring intraprostatically immediately following epithelium-specific Pten deletion without expansion in hematopoietic tissues. Prostatic Gr-1(+) CD11b(+) cells, but not those isolated from the spleen of the same tumor-bearing mice, suppress T cell proliferation and express high levels of Arginase 1 and iNOS. Mechanistically, the loss of PTEN in the epithelium leads to a significant upregulation of genes within the inflammatory response and cytokine-cytokine receptor interaction pathways, including Csf1 and Il1b, two genes known to induce MDSC expansion and immunosuppressive activities.
28228279Uterine leiomyosarcomaPromote immunity; increase the efficacy of immunotherapyIn summary, immunohistochemical, whole-exome, and whole-transcriptome analyses of pre-treatment and treatment-resistant tumors from one patient have identified PTEN loss and changes in neoantigen expression as potential clinical mechanisms of acquired resistance to immune checkpoint therapy, although further experimental work in mesenchymal tumors is needed.
29309058Prostate carcinomaInhibit immunity (infiltration)Loss of PTEN with loss of ZBTB7A or loss of PTEN with loss of TRP53 in mice showed enhanced Gr-1+CD11b+ MDSCs cells infiltration, and recruited T cells and M2-like marcophage. Thus, could promote immune evasion. However, loss of PTEN with loss of PML in mice does not increase immune infiltration. The evasion effect is combination dependent. The Ptenpc?/?; Pmlpc?/? tumors still had limited immune infiltrate, whereas the Ptenpc?/?; Zbtb7apc?/? immunological landscape was dominated by Gr-1+CD11b+ cells. The Gr-1+CD11b+ population was also elevated in Ptenpc?/?; Trp53pc?/? mice, and there was a marked recruitment of T cells and macrophages. Interestingly, further analysis revealed that most macrophages had an M2-like phenotype (CD11b+F4/80+CD206+) and that the increase in CD3+ cells reflected the recruitment of CD4+FoxP3+ T regulatory (Treg) cells, thus defining a potentially favorable microenvironment for cancer immunological evasion.
17159987GliomaInhibit immunity (T cell function)Here we show that expression of the gene encoding B7-H1 increases post transcriptionally in human glioma after loss of phosphatase and tensin homolog (PTEN) and activation of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway.
25015834glioblastomaPromote immunityGenetic and pharmacologic experimental approaches in vitro, as well as in vivo autoimmunity models, provide convincing evidence that PI3K/PTEN-regulated extracellular Arginase I acts as a paracrine regulator of inflammation and immunity.
29686284Prostate CarcinomaPromote immunityHere we show that a patient-derived prostate-specific microbe, CP1, in combination with anti-PD-1 immunotherapy, increases survival and decreases tumor burden in orthotopic MYC- and PTEN-mutant prostate cancer models.
24141770MelanomaPromote immunityPTEN functions as a melanoma tumor suppressor by promoting host immune response. Mechanistically, PTEN represses the expression of immunosuppressive cytokines by blocking the phosphatidylinositide 3-kinase (PI3K) pathway. In melanoma cells lacking PTEN, signal transducer and activator of transcription 3 activates the transcription of immunosuppressive cytokines in a PI3K-dependent manner. Furthermore, we report that PTEN, as an alternative mechanism to promote the host immune response against cancer cells, represses the expression of programmed cell death 1 ligand, a known repressor of the host immune response.
22037217Head and Neck Squamous Cell CarcinomaPromote immunityLoss of TGF-β signaling and PTEN promotes head and neck squamous cell carcinoma through cellular senescence evasion and cancer-related inflammation. Conditional activation of the PI3K/Akt pathway due to Pten deletion in the mouse head and neck epithelia gives rise to hyperproliferation, but only a few lesions progress to HNSCC. Molecular analysis revealed enhanced cell proliferation, decreased apoptosis, and increased expression of CCND1 in the basal layer of the head and neck epithelia, as well as in the tumors of Tgfbr1/Pten double conditional knockout (2cKO) mice.
29704427Breast CarcinomaPromote immunityCo-immunoprecipitation and immunofluorescence cell staining assays revealed that interaction of Plac1 and Furin degraded Notch1 and generated Notch1 intracellular domain (NICD) that could inhibit PTEN activity. A rescue study showed that inhibition of Furin and overexpression of PTEN in Plac1 overexpression cells blocked Plac1-induced tumor cell progression.
25223704lung carcinomaPromote immunityPTEN is a negative modulator of CD4+CD25highFoxp3+ Treg homeostasis in vivo and expansion ex vivo
25092892lymphomaPromote immunityOur data indicate that IFN-gamma beefs up macrophage innate response and cytotoxicity by downregulating miR-3473b to release PTEN from suppression, and then the increase of PTEN contributes to the full activation of IFN-gamma-primed macrophages.
21972292MelanomaInhibit immunityMechanistically, we identified Pten (phosphatase and tensin homolog) as the functionally important target of miR-19b, whereas the function of miR-17 is mediated by TGFβRII and the novel target CREB1.In the present study, we showed that Pten is the dominant functionally relevant target of miR-19b in CD4 T cells. The ability of Pten to suppress T-cell proliferation and survival through its antagonizing effect on the PI3K-Akt pathway is well documented
Summary
SymbolPTEN
Namephosphatase and tensin homolog
Aliases MMAC1; PTEN1; mutated in multiple advanced cancers 1; BZS; MHAM; CWS1; DEC; GLM2; MMAC11; MMAC1 phosphatase ......
Chromosomal Location10q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of PTEN in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolPTEN
Namephosphatase and tensin homolog
Aliases MMAC1; PTEN1; mutated in multiple advanced cancers 1; BZS; MHAM; CWS1; DEC; GLM2; MMAC11; MMAC1 phosphatase ......
Chromosomal Location10q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of PTEN in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.2730.289
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.0210.99
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.460.705
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1860.622
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.5210.802
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.2370.928
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.3070.5
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.3150.868
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2280.917
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.4850.704
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.740.713
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1970.00913
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of PTEN in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277314.85.59.30.206
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 014014.3-14.31
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275914.83.411.40.0746
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.509.50.492
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131115.4015.40.482
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38277.93.74.20.636
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.57.7-3.21
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161412.5012.50.485
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolPTEN
Namephosphatase and tensin homolog
Aliases MMAC1; PTEN1; mutated in multiple advanced cancers 1; BZS; MHAM; CWS1; DEC; GLM2; MMAC11; MMAC1 phosphatase ......
Chromosomal Location10q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PTEN. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolPTEN
Namephosphatase and tensin homolog
Aliases MMAC1; PTEN1; mutated in multiple advanced cancers 1; BZS; MHAM; CWS1; DEC; GLM2; MMAC11; MMAC1 phosphatase ......
Chromosomal Location10q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PTEN. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PTEN.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolPTEN
Namephosphatase and tensin homolog
Aliases MMAC1; PTEN1; mutated in multiple advanced cancers 1; BZS; MHAM; CWS1; DEC; GLM2; MMAC11; MMAC1 phosphatase ......
Chromosomal Location10q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PTEN. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolPTEN
Namephosphatase and tensin homolog
Aliases MMAC1; PTEN1; mutated in multiple advanced cancers 1; BZS; MHAM; CWS1; DEC; GLM2; MMAC11; MMAC1 phosphatase ......
Chromosomal Location10q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of PTEN expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolPTEN
Namephosphatase and tensin homolog
Aliases MMAC1; PTEN1; mutated in multiple advanced cancers 1; BZS; MHAM; CWS1; DEC; GLM2; MMAC11; MMAC1 phosphatase ......
Chromosomal Location10q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between PTEN and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolPTEN
Namephosphatase and tensin homolog
Aliases MMAC1; PTEN1; mutated in multiple advanced cancers 1; BZS; MHAM; CWS1; DEC; GLM2; MMAC11; MMAC1 phosphatase ......
Chromosomal Location10q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting PTEN collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting PTEN.
ID Name Drug Type Targets #Targets
DB04327PhosphatidylethanolamineSmall MoleculePROCR, PTEN2