pten (ptenA) is the Dictyostelium discoideum ortholog of the tumor suppressor PTEN, a phosphoinositide 3-phosphatase that removes the phosphate at the D3 position of the inositol ring of phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3), regenerating PtdIns(4,5)P2 and thereby acting as the direct antagonist of PI3-kinase. The protein has an N-terminal tensin-type phosphatase domain and a C-terminal C2 domain; in vitro it also displays dual-specificity protein phosphatase activity and soluble inositol-polyphosphate 3-phosphatase activity, but its physiologically dominant activity is lipid PIP3 phosphatase. PTEN is a peripheral membrane protein that binds PtdIns(4,5)P2 via an N-terminal basic motif; in chemotaxing cells it is enriched on the plasma membrane of the lateral sides and rear (uropod/trailing edge) and is depleted from the leading edge, showing a distribution reciprocal to PI3-kinase. By restricting PIP3 to the anterior, PTEN establishes and maintains front-rear polarity, suppresses lateral pseudopod formation, and enables efficient chemotaxis toward cAMP. It also localizes to the cleavage furrow and equatorial cortex during division, where it contributes to cortical myosin II accumulation and cytokinesis, and participates in chemorepulsion, bleb regulation, and density-dependent control of proliferation. Loss of PTEN elevates PIP3 and PKB/Akt (PkbA) substrate phosphorylation, causing broadened PIP3 responses, excess pseudopods, impaired chemotaxis, multinucleation, and aggregation defects.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0016314
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Phylogenetic inference of PIP3 3-phosphatase activity is the defining and experimentally corroborated core molecular function of PTEN in Dictyostelium.
Reason: The lipid phosphatase activity of PTEN toward PIP3 is well established and is the physiologically dominant activity of this enzyme, directly antagonizing PI3-kinase during chemotaxis.
Supporting Evidence:
PMID:14764604
the lipid phosphatase activity of PTEN mediates chemotaxis and that the sharp localization of PI(3,4,5)P3 requires localization of PTEN to the rear of the cell
|
|
GO:0051726
regulation of cell cycle
|
IBA
GO_REF:0000033 |
MARK AS OVER ANNOTATED |
Summary: This IBA transfer from the PTEN/tensin family reflects the mammalian tumor-suppressor role in cell-cycle control. In Dictyostelium the documented cell-division phenotype is a cytokinesis (multinucleation) defect, not regulation of cell-cycle progression per se.
Reason: There is no direct evidence that Dictyostelium PTEN regulates cell-cycle progression; the observed division phenotype is failed cytokinesis, which is captured more precisely by GO:0000281 mitotic cytokinesis. The general cell-cycle term is an over-propagation from mammalian orthologs.
Propagation Review
Root cause:
PROPAGATION BAD
Failure modes:
FUNCTIONAL DIVERGENCE
Sources checked:
PANTHER:PTN000959472
· PANTHER node for the PTEN/tensin phosphatase family
SUPPORTS SOURCE BUT NOT TARGET
Cell-cycle regulation reflects the mammalian tumor-suppressor role of PTEN; Dictyostelium PTEN acts as a PIP3 phosphatase in chemotaxis with no evidence of cell-cycle control
UniProtKB:P60484
· human PTEN
SUPPORTS SOURCE BUT NOT TARGET
Mammalian PTEN regulates the cell cycle as a tumor suppressor; this role has diverged and is unsupported in Dictyostelium
Supporting Evidence:
PMID:19515202
PTEN knockout (pten(-)) cells became multinucleated, and myosin II significantly decreased in amount at the furrow
|
|
GO:0005634
nucleus
|
IBA
GO_REF:0000033 |
REMOVE |
Summary: Nuclear localization is inferred phylogenetically from mammalian PTEN, which has documented nuclear tumor-suppressor functions. Dictyostelium PTEN is consistently reported as a peripheral plasma-membrane, cortical and cytosolic protein, with no evidence of nuclear localization or function.
Reason: This is an IBA over-propagation. All experimental localization data for Dictyostelium PTEN place it at the plasma membrane (rear/lateral), cortex/furrow, and cytosol; none support nuclear localization. The nuclear role is a mammal-specific attribute that does not transfer to this ortholog.
Propagation Review
Root cause:
PROPAGATION BAD
Failure modes:
COMPARTMENT OR COMPLEX MISMATCH
Sources checked:
PANTHER:PTN000959472
· PANTHER node for the PTEN/tensin phosphatase family
SUPPORTS SOURCE BUT NOT TARGET
Nuclear localization derives from mammalian PTEN; all experimental Dictyostelium PTEN localization is plasma-membrane and cytosolic
UniProtKB:P60484
· human PTEN
SUPPORTS SOURCE BUT NOT TARGET
Mammalian PTEN has a documented nuclear pool; Dictyostelium PTEN does not localize to the nucleus
Supporting Evidence:
PMID:12062103
Exogenously expressed PTEN-GFP localized to the surface membrane at the rear of the cell
|
|
GO:0005886
plasma membrane
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Plasma membrane localization is strongly supported by direct evidence; PTEN is a peripheral membrane protein enriched at the rear and lateral sides of chemotaxing cells.
Reason: PTEN functions as a peripheral membrane phosphatase acting on membrane PIP3, and its rear/lateral plasma-membrane localization is directly observed.
Supporting Evidence:
PMID:12062103
Exogenously expressed PTEN-GFP localized to the surface membrane at the rear of the cell
|
|
GO:0051896
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: PTEN regulates PI3K/PKB signaling by degrading PIP3. The direction is negative (see GO:0051898), but this general regulation term is not incorrect.
Reason: By dephosphorylating PIP3, PTEN is a bona fide regulator of the PI3K/PKB (PkbA) pathway; loss of PTEN elevates and prolongs PKB substrate phosphorylation.
Supporting Evidence:
PMID:21169559
The polarity defects in pten- cells correlate with elevated phosphorylations of PKB substrates
|
|
GO:0005829
cytosol
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: A cytosolic pool of PTEN exists and is directly observed; PTEN redistributes between the plasma membrane and the cytosol during signaling.
Reason: PTEN cycles on and off the membrane and has a genuine cytosolic pool, supported by direct imaging and consistent with its soluble inositol-phosphatase activity.
Supporting Evidence:
PMID:23132928
redistribution of PTEN to the cytosol
|
|
GO:0004725
protein tyrosine phosphatase activity
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: Protein tyrosine (dual-specificity) phosphatase activity is a family-level attribute inherited from the PTEN/tensin catalytic fold. It is a biochemical capability of PTEN but is not the physiologically dominant activity, which is lipid PIP3 phosphatase.
Reason: The PTEN active site can dephosphorylate phosphotyrosine in vitro, but no protein-phosphatase substrate or physiological role has been demonstrated for Dictyostelium PTEN. Retain as a non-core catalytic capability.
|
|
GO:0004722
protein serine/threonine phosphatase activity
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: Serine/threonine (dual-specificity) protein phosphatase activity derives from EC 3.1.3.16 mapping to the PTEN catalytic domain. It is a possible in-vitro capability but not a demonstrated physiological function.
Reason: PTEN is a dual-specificity phosphatase by similarity, but its dominant physiological role is lipid PIP3 dephosphorylation; no protein ser/thr substrate is documented in Dictyostelium.
|
|
GO:0004725
protein tyrosine phosphatase activity
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: Duplicate protein tyrosine phosphatase assignment from automated EC mapping; same rationale as the IBA protein tyrosine phosphatase annotation.
Reason: A biochemical capability of the PTEN fold, not the core physiological activity in Dictyostelium.
|
|
GO:0005737
cytoplasm
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: General cytoplasmic localization from UniProt subcellular-location mapping; consistent with PTEN's cytosolic and cortical pools.
Reason: PTEN is a cytoplasmic (peripheral membrane/cytosolic) protein, directly supported by imaging.
Supporting Evidence:
PMID:23132928
redistribution of PTEN to the cytosol
|
|
GO:0005886
plasma membrane
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Plasma membrane localization from UniProt mapping, strongly corroborated by direct imaging of PTEN-GFP at the rear membrane.
Reason: PTEN is a peripheral plasma-membrane protein acting on membrane PIP3.
Supporting Evidence:
PMID:12062103
Exogenously expressed PTEN-GFP localized to the surface membrane at the rear of the cell
|
|
GO:0005938
cell cortex
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Cortical localization from UniProt mapping; PTEN is constitutively localized in the cortex of polarized cells.
Reason: Directly supported experimental cortical localization in polarized cells.
Supporting Evidence:
PMID:17623773
PTEN, which is constitutively localized in the cortex of polarized cells
|
|
GO:0016314
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: Automated assignment of the core PIP3 3-phosphatase activity; redundant with and consistent with the IBA/ISS/experimental support.
Reason: This is the defining core molecular function of PTEN.
Supporting Evidence:
PMID:14764604
the lipid phosphatase activity of PTEN mediates chemotaxis
|
|
GO:0016791
phosphatase activity
|
IEA
GO_REF:0000002 |
KEEP AS NON CORE |
Summary: Grandparent-level generic phosphatase term from InterPro2GO. Not incorrect, but uninformative given the specific PIP3 3-phosphatase activity is annotated.
Reason: The specific term GO:0016314 (PIP3 3-phosphatase activity) captures the core function; the generic phosphatase term is redundant and low-information.
|
|
GO:0030351
inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity
|
IEA
GO_REF:0000116 |
KEEP AS NON CORE |
Summary: Soluble inositol-polyphosphate 3-phosphatase activity toward Ins(1,3,4,5,6)P5, assigned by Rhea mapping and by similarity to human PTEN. Plausible but not experimentally demonstrated in Dictyostelium.
Reason: PTEN can act as a cytosolic inositol 3-phosphatase by similarity, but this is a secondary activity relative to its core lipid PIP3 phosphatase role.
|
|
GO:0031038
myosin II filament organization
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: PTEN promotes cortical/posterior myosin II accumulation, so involvement in myosin II organization is supported, but this is a downstream consequence of PIP3 regulation rather than a core molecular function.
Reason: PTEN acts upstream to localize myosin II; a genuine but downstream process, not the core activity.
Supporting Evidence:
PMID:19515202
PTEN and myosin II co-localized at the posterior of migrating cells and furrow region of dividing cells
|
|
GO:0031152
aggregation involved in sorocarp development
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: pten- cells fail to aggregate normally, so a developmental role in aggregation is supported (also annotated by IMP), but this is a downstream developmental phenotype, not a core molecular function.
Reason: Aggregation defects are a downstream consequence of impaired chemotaxis/polarity; retain as non-core developmental role.
Supporting Evidence:
PMID:25247494
Deletion of ptenA results in defects in motility, chemotaxis, aggregation and multicellular morphogenesis
|
|
GO:0046580
negative regulation of Ras protein signal transduction
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: PTEN (with CnrN) locally inhibits Ras activation, supporting this process; consistent with the IMP annotation from the same phenomenon.
Reason: Supported downstream process; PTEN restrains Ras activity, but this is a pathway-level effect of PIP3 regulation rather than a core molecular activity.
Supporting Evidence:
PMID:38940195
require both PTEN and CnrN to locally inhibit Ras activation
|
|
GO:0050793
regulation of developmental process
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: Very general developmental regulation term inferred by ARBA; pten- has developmental (aggregation/morphogenesis) defects but this term is too broad to be informative.
Reason: More specific developmental terms (aggregation involved in sorocarp development) capture the phenotype; this broad term is non-core.
Supporting Evidence:
PMID:25247494
Deletion of ptenA results in defects in motility, chemotaxis, aggregation and multicellular morphogenesis
|
|
GO:0051489
regulation of filopodium assembly
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: PTEN influences filopod size/formation, supporting a role in filopodium regulation, but as a downstream cytoskeletal effect of PIP3 control.
Reason: Downstream cytoskeletal regulation; retain as non-core.
Supporting Evidence:
PMID:38940195
AprA requires both PTEN and CnrN to increase PI(4,5)P2 levels, decrease PI(3,4,5)P3 levels, inhibit proliferation, decrease myosin II phosphorylation and increase filopod sizes
|
|
GO:0051717
inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
|
IEA
GO_REF:0000116 |
KEEP AS NON CORE |
Summary: Soluble inositol-phosphate 3-phosphatase activity toward Ins(1,3,4,5)P4, assigned by Rhea mapping and by similarity. Plausible secondary activity, not demonstrated in Dictyostelium.
Reason: Secondary soluble inositol-phosphatase capability by similarity; not the core lipid phosphatase function.
|
|
GO:0051898
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: PTEN negatively regulates PI3K/PKB signaling by degrading PIP3; this is a core biological role, also supported by IMP.
Reason: Loss of PTEN elevates and prolongs PKB (PkbA) substrate phosphorylation, directly demonstrating negative regulation of this pathway.
Supporting Evidence:
PMID:21169559
The polarity defects in pten- cells correlate with elevated phosphorylations of PKB substrates
|
|
GO:0052866
phosphatidylinositol phosphate phosphatase activity
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: General phosphatidylinositol-phosphate phosphatase term; a parent of the specific PIP3 3-phosphatase activity.
Reason: The specific PIP3 3-phosphatase term is the informative core function; this parent term is redundant.
|
|
GO:0140986
G protein-coupled chemorepellent receptor signaling pathway
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: PTEN is required for AprA-induced chemorepulsion, supporting involvement in chemorepellent GPCR signaling (also annotated by IMP).
Reason: Genuine but specialized downstream signaling role; not the core molecular function.
Supporting Evidence:
PMID:38940195
Dictyostelium discoideum cells require both PTEN and CnrN to induce chemorepulsion of cells away from the secreted chemorepellent protein AprA
|
|
GO:1903665
negative regulation of asexual reproduction
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: PTEN participates in density/polyphosphate-dependent proliferation inhibition, supporting negative regulation of asexual reproduction (proliferation), also annotated by IMP.
Reason: Supported downstream role in proliferation control; not a core molecular activity.
Supporting Evidence:
PMID:34154396
Polyphosphate upregulates IP3, and this requires GrlD, GefA, PTEN, PLC, and PiaA
|
|
GO:0004722
protein serine/threonine phosphatase activity
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Serine/threonine protein phosphatase activity transferred by sequence similarity from human PTEN. A dual-specificity capability, not the core role.
Reason: Biochemical capability by similarity; the physiological function is lipid PIP3 dephosphorylation.
|
|
GO:0004725
protein tyrosine phosphatase activity
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Protein tyrosine phosphatase activity transferred by similarity from human PTEN; a capability of the PTEN fold, not the dominant activity.
Reason: Non-core dual-specificity capability by similarity.
|
|
GO:0016314
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: Core PIP3 3-phosphatase activity transferred by sequence similarity from human PTEN and corroborated experimentally in Dictyostelium.
Reason: This is the defining core molecular function of PTEN.
Supporting Evidence:
PMID:14764604
the lipid phosphatase activity of PTEN mediates chemotaxis
|
|
GO:0030351
inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Soluble Ins(1,3,4,5,6)P5 3-phosphatase activity by similarity; a plausible secondary activity.
Reason: Secondary soluble inositol-phosphatase capability, not the core lipid phosphatase function.
|
|
GO:0051717
inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Soluble Ins(1,3,4,5)P4 3-phosphatase activity by similarity; a plausible secondary activity.
Reason: Secondary soluble inositol-phosphatase capability, not the core function.
|
|
GO:0031273
negative regulation of pseudopodium assembly
|
IMP
PMID:38940195 PTEN and the PTEN-like phosphatase CnrN have both distinct a... |
ACCEPT |
Summary: Suppression of pseudopod formation is a hallmark PTEN function; by degrading PIP3 at the sides and rear, PTEN restrains lateral pseudopod assembly, which is central to directed migration and chemorepulsion.
Reason: A well-supported core biological role of PTEN; pten- cells cannot suppress lateral pseudopods, and PTEN is required for AprA-induced pseudopod inhibition.
Supporting Evidence:
PMID:17623773
PTEN, therefore, plays a fundamental role in the suppression of lateral pseudopod formation
|
|
GO:0051490
negative regulation of filopodium assembly
|
IMP
PMID:38940195 PTEN and the PTEN-like phosphatase CnrN have both distinct a... |
KEEP AS NON CORE |
Summary: PTEN affects filopod size/number in the AprA chemorepulsion pathway; supported downstream cytoskeletal regulation.
Reason: Genuine but downstream cytoskeletal effect of PIP3 control; non-core.
Supporting Evidence:
PMID:38940195
AprA requires both PTEN and CnrN to increase PI(4,5)P2 levels, decrease PI(3,4,5)P3 levels, inhibit proliferation, decrease myosin II phosphorylation and increase filopod sizes
|
|
GO:0046580
negative regulation of Ras protein signal transduction
|
IMP
PMID:38940195 PTEN and the PTEN-like phosphatase CnrN have both distinct a... |
KEEP AS NON CORE |
Summary: PTEN (together with CnrN) is required to locally inhibit Ras activation, a genuine signaling role demonstrated by mutant analysis, though it is a downstream pathway effect rather than the core molecular function.
Reason: Experimentally supported: pten- cells fail to locally inhibit Ras activation, linking PTEN to negative regulation of Ras signaling; this is a downstream signaling consequence of PIP3 restriction, kept consistent with the IEA annotation to the same term.
Supporting Evidence:
PMID:38940195
require both PTEN and CnrN to locally inhibit Ras activation
|
|
GO:0031038
myosin II filament organization
|
IMP
PMID:38940195 PTEN and the PTEN-like phosphatase CnrN have both distinct a... |
KEEP AS NON CORE |
Summary: PTEN influences myosin II phosphorylation/organization; a downstream cytoskeletal consequence of PIP3 regulation.
Reason: Supported downstream role in myosin II regulation; not a core molecular activity.
Supporting Evidence:
PMID:38940195
AprA requires both PTEN and CnrN to increase PI(4,5)P2 levels, decrease PI(3,4,5)P3 levels, inhibit proliferation, decrease myosin II phosphorylation and increase filopod sizes
|
|
GO:1903665
negative regulation of asexual reproduction
|
IMP
PMID:38940195 PTEN and the PTEN-like phosphatase CnrN have both distinct a... |
KEEP AS NON CORE |
Summary: PTEN is required for AprA-mediated inhibition of proliferation, linking it to negative regulation of asexual reproduction.
Reason: Supported downstream role in proliferation control; non-core.
Supporting Evidence:
PMID:38940195
AprA requires both PTEN and CnrN to increase PI(4,5)P2 levels, decrease PI(3,4,5)P3 levels, inhibit proliferation, decrease myosin II phosphorylation and increase filopod sizes
|
|
GO:0051898
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
|
IMP
PMID:21169559 Disruption of PKB signaling restores polarity to cells lacki... |
ACCEPT |
Summary: Directly supported core role; disruption of PTEN elevates and prolongs PKB (PkbA) substrate phosphorylation, and the polarity defects track with this hyperphosphorylation.
Reason: Strong experimental support for PTEN as a negative regulator of the PI3K/PKB pathway in Dictyostelium.
Supporting Evidence:
PMID:21169559
The polarity defects in pten- cells correlate with elevated phosphorylations of PKB substrates
|
|
GO:0051896
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
|
IMP
PMID:20562345 Self-organization of the phosphatidylinositol lipids signali... |
ACCEPT |
Summary: PTEN, with PI3K, regulates the spatiotemporal dynamics of PtdIns lipids and is essential for self-organized PIP3 waves underlying migration.
Reason: Experimentally supported regulatory role in the PI3K/PIP3 signaling system; PTEN is essential for the lipid wave dynamics.
Supporting Evidence:
PMID:20562345
regulators for PtdIns lipid concentrations along the membrane, were essential for wave generation
|
|
GO:0001931
uropod
|
IDA
PMID:19515202 PTEN is a mechanosensing signal transducer for myosin II loc... |
ACCEPT |
Summary: PTEN localizes to the posterior (uropod) of migrating cells, directly observed by fluorescence imaging, consistent with its rear-restricted role.
Reason: Direct imaging places PTEN at the posterior/uropod of migrating cells.
Supporting Evidence:
PMID:19515202
PTEN and myosin II co-localized at the posterior of migrating cells and furrow region of dividing cells
|
|
GO:0005829
cytosol
|
TAS
PMID:15473840 Chemoattractant signaling in dictyostelium discoideum. |
ACCEPT |
Summary: A cytosolic pool of PTEN is described; PTEN cycles between the plasma membrane and cytosol during chemoattractant signaling.
Reason: Consistent with directly observed cytosolic redistribution of PTEN.
Supporting Evidence:
PMID:23132928
redistribution of PTEN to the cytosol
|
|
GO:0031254
cell trailing edge
|
IDA
PMID:19011688 Ordered patterns of cell shape and orientational correlation... |
ACCEPT |
Summary: PTEN is directly observed to localize at the rear/trailing edge of spontaneously migrating cells, where it restricts excess pseudopod formation.
Reason: Direct imaging localizes PTEN to the cell rear/trailing edge.
Supporting Evidence:
PMID:19011688
phosphatase and tensin homolog, (PTEN), is simultaneously localized at the rear
|
|
GO:0031257
cell trailing edge membrane
|
IDA
PMID:12062104 Spatial and temporal regulation of 3-phosphoinositides by PI... |
ACCEPT |
Summary: PTEN shows a distribution reciprocal to PI3K, occupying the plasma membrane along the lateral sides and posterior of chemotaxing cells.
Reason: Directly supported rear-membrane localization; PTEN's reciprocal distribution to PI3K places it on the trailing-edge membrane.
Supporting Evidence:
PMID:12062104
PTEN, a negative regulator of PI3K pathways, exhibits a reciprocal pattern of localization
|
|
GO:0032154
cleavage furrow
|
IDA
PMID:19515202 PTEN is a mechanosensing signal transducer for myosin II loc... |
ACCEPT |
Summary: PTEN localizes to the furrow region of dividing cells, directly observed together with myosin II.
Reason: Direct imaging places PTEN at the cleavage furrow during cytokinesis.
Supporting Evidence:
PMID:19515202
PTEN and myosin II co-localized at the posterior of migrating cells and furrow region of dividing cells
|
|
GO:0051285
cell cortex of cell tip
|
IDA
PMID:17623773 PTEN plays a role in the suppression of lateral pseudopod fo... |
ACCEPT |
Summary: PTEN is constitutively localized in the cortex of polarized cells, including at cell tips/pseudopod-suppressing cortical regions.
Reason: Directly supported constitutive cortical localization in polarized cells.
Supporting Evidence:
PMID:17623773
PTEN, which is constitutively localized in the cortex of polarized cells
|
|
GO:1990753
equatorial cell cortex
|
IDA
PMID:19515202 PTEN is a mechanosensing signal transducer for myosin II loc... |
ACCEPT |
Summary: During division PTEN accumulates at the equatorial/furrow cortex, where it contributes to myosin II accumulation and cytokinesis.
Reason: Direct imaging localizes PTEN to the equatorial cortex/furrow of dividing cells.
Supporting Evidence:
PMID:19515202
PTEN and myosin II co-localized at the posterior of migrating cells and furrow region of dividing cells
|
|
GO:0140986
G protein-coupled chemorepellent receptor signaling pathway
|
IMP
PMID:30462573 An endogenous chemorepellent directs cell movement by inhibi... |
KEEP AS NON CORE |
Summary: PTEN localizes myosin II to the rear during chemorepulsion; it is part of the AprA chemorepellent GPCR signaling response.
Reason: Genuine but specialized downstream signaling role in chemorepulsion.
Supporting Evidence:
PMID:30462573
PTEN to localize myosin II to the rear of a cell
|
|
GO:0030010
establishment of cell polarity
|
IMP
PMID:21169559 Disruption of PKB signaling restores polarity to cells lacki... |
ACCEPT |
Summary: By restricting PIP3, PTEN establishes and maintains front-rear polarity required for cytokinesis and chemotaxis; a core biological role.
Reason: Strongly supported; loss of PTEN causes loss of polarity, and PTEN is required to maintain the polarity underlying directed migration and division.
Supporting Evidence:
PMID:21169559
tumor suppressor PTEN not only controls cell growth but also maintains cell polarity required for cytokinesis and chemotaxis
|
|
GO:0036052
protein localization to uropod
|
IMP
PMID:19515202 PTEN is a mechanosensing signal transducer for myosin II loc... |
KEEP AS NON CORE |
Summary: PTEN acts upstream to recruit/localize myosin II to the posterior (uropod), accumulating there prior to myosin II.
Reason: Downstream effect of PTEN's rear localization and PIP3 restriction; not the core molecular activity.
Supporting Evidence:
PMID:19515202
During pseudopod retraction and cell aspiration by microcapillary, PTEN accumulated at the tips of pseudopods and aspirated lobes prior to the accumulation of myosin II
|
|
GO:0080025
phosphatidylinositol-3,5-bisphosphate binding
|
IDA
PMID:35186938 Gradients of PI(4,5)P(2) and PI(3,5)P(2) Jointly Participate... |
KEEP AS NON CORE |
Summary: In vitro, PTEN preferentially bound liposomes containing PI(4,5)P2 and PI(3,5)P2, indicating PI(3,5)P2 binding capacity that may contribute to back (rear) membrane localization.
Reason: Directly demonstrated lipid-binding property that supports membrane targeting to the back, but distinct from the core catalytic function.
Supporting Evidence:
PMID:35186938
Pten preferentially bound to liposomes containing PI(4,5)P2 and PI(3,5)P2
|
|
GO:0005829
cytosol
|
IDA
PMID:23132928 Delineating the core regulatory elements crucial for directe... |
ACCEPT |
Summary: Direct imaging shows PTEN redistributing to the cytosol upon stimulation and residing in the cytoplasm when membrane PI(4,5)P2 is depleted.
Reason: Directly supported cytosolic pool of PTEN.
Supporting Evidence:
PMID:23132928
redistribution of PTEN to the cytosol
|
|
GO:1903665
negative regulation of asexual reproduction
|
IMP
PMID:34154396 An Autocrine Negative Feedback Loop Inhibits Dictyostelium d... |
KEEP AS NON CORE |
Summary: PTEN is required for polyphosphate-mediated inhibition of proliferation, acting within a density-sensing autocrine feedback loop.
Reason: Supported downstream role in density-dependent proliferation control; non-core.
Supporting Evidence:
PMID:34154396
Polyphosphate upregulates IP3, and this requires GrlD, GefA, PTEN, PLC, and PiaA
|
|
GO:0032060
bleb assembly
|
IMP
PMID:26317626 Microtubule-Mediated Inositol Lipid Signaling Plays Critical... |
KEEP AS NON CORE |
Summary: PTEN-null cells extend fewer blebs, implicating PTEN in bleb regulation via inositol lipid metabolism.
Reason: Supported downstream role in blebbing through PIP3/PIP2 balance; not the core molecular activity.
Supporting Evidence:
PMID:26317626
PTEN-null cells extended fewer blebs
|
|
GO:0005546
phosphatidylinositol-4,5-bisphosphate binding
|
IDA
PMID:32111929 Single-molecule imaging of PI(4,5)P(2) and PTEN in vitro rev... |
ACCEPT |
Summary: PTEN binds its enzymatic product PI(4,5)P2, which stabilizes its membrane binding in a basic-residue-dependent, positive-feedback manner and drives its posterior accumulation.
Reason: Directly demonstrated PI(4,5)P2 binding is central to PTEN's rear membrane targeting mechanism and to restricting PIP3 to the anterior.
Supporting Evidence:
PMID:32111929
the enzymatic product, PI(4,5)P2, stabilizes PTEN's membrane-binding
|
|
GO:0034485
phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity
|
IDA
PMID:14764604 Novel mechanism of PTEN regulation by its phosphatidylinosit... |
UNDECIDED |
Summary: This annotation assigns 5-phosphatase activity (the reaction catalyzed by SHIP-type enzymes, yielding PI(3,4)P2), which conflicts with PTEN's well-established mechanism as a D3 (3-position) phosphatase. The cited abstract does not describe 5-phosphatase activity and the full text is not available to verify the experimental basis.
Reason: PTEN is defined mechanistically as a PIP3 3-phosphatase; a 5-phosphatase activity is inconsistent with this. As the relevant full text cannot be accessed to confirm the assay, this is flagged UNDECIDED rather than removed, per policy on unverifiable experimental annotations.
|
|
GO:0051800
phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
|
IDA
PMID:14764604 Novel mechanism of PTEN regulation by its phosphatidylinosit... |
KEEP AS NON CORE |
Summary: PTEN also dephosphorylates PtdIns(3,4)P2 at the 3-position, consistent with its D3 phosphatase mechanism and with UniProt substrate annotation. This is a genuine but secondary activity relative to the preferred PIP3 substrate.
Reason: PI(3,4)P2 is a documented secondary substrate of PTEN; the core activity is PIP3 3-phosphatase, so this is retained as non-core.
|
|
GO:0043491
phosphatidylinositol 3-kinase/protein kinase B signal transduction
|
IMP
PMID:12062104 Spatial and temporal regulation of 3-phosphoinositides by PI... |
KEEP AS NON CORE |
Summary: PTEN acts within the PI3K/PKB pathway; disruption prolongs and broadens PIP3-dependent (PH-domain) responses. The negative-regulation aspect is better captured by GO:0051898.
Reason: PTEN acts upstream within this pathway as its negative regulator; the specific negative-regulation term is the more informative core annotation.
Supporting Evidence:
PMID:12062103
Disruption of the PI 3-phosphatase, PTEN, in Dictyostelium discoideum dramatically prolonged and broadened the PH domain relocation and actin polymerization responses
|
|
GO:0005886
plasma membrane
|
IDA
PMID:12062103 Tumor suppressor PTEN mediates sensing of chemoattractant gr... |
ACCEPT |
Summary: PTEN-GFP directly localizes to the plasma membrane at the rear of the cell; membrane localization requires the PI(4,5)P2-binding motif.
Reason: Directly observed plasma-membrane localization essential for function.
Supporting Evidence:
PMID:12062103
Exogenously expressed PTEN-GFP localized to the surface membrane at the rear of the cell
|
|
GO:0030041
actin filament polymerization
|
IMP
PMID:12062103 Tumor suppressor PTEN mediates sensing of chemoattractant gr... |
KEEP AS NON CORE |
Summary: Loss of PTEN broadens and prolongs actin polymerization responses; PTEN acts upstream of actin dynamics via PIP3 restriction rather than directly polymerizing actin.
Reason: Downstream cytoskeletal consequence of PIP3 regulation; not a core molecular activity.
Supporting Evidence:
PMID:12062103
Disruption of the PI 3-phosphatase, PTEN, in Dictyostelium discoideum dramatically prolonged and broadened the PH domain relocation and actin polymerization responses
|
|
GO:0031269
pseudopodium assembly
|
IMP
PMID:12062103 Tumor suppressor PTEN mediates sensing of chemoattractant gr... |
KEEP AS NON CORE |
Summary: PTEN regulates pseudopod formation; its normal role is to restrict pseudopods to the front, and loss leads to broadened/excess pseudopod responses.
Reason: Downstream morphogenetic process controlled via PIP3; the negative regulation of pseudopodia is the more informative aspect. Non-core.
Supporting Evidence:
PMID:12062103
Disruption of the PI 3-phosphatase, PTEN, in Dictyostelium discoideum dramatically prolonged and broadened the PH domain relocation and actin polymerization responses
|
|
GO:0043327
chemotaxis to cAMP
|
IMP
PMID:12062103 Tumor suppressor PTEN mediates sensing of chemoattractant gr... |
ACCEPT |
Summary: PTEN is required for efficient cAMP chemotaxis; pten- cells follow circuitous routes toward the attractant. A core biological role.
Reason: Strongly supported; PTEN-mediated gradient sensing/polarity is required for directional migration toward cAMP.
Supporting Evidence:
PMID:12062103
causing the cells lacking PTEN to follow a circuitous route toward the attractant
|
|
GO:0000281
mitotic cytokinesis
|
IMP
PMID:19515202 PTEN is a mechanosensing signal transducer for myosin II loc... |
ACCEPT |
Summary: PTEN is required for cytokinesis; pten- cells become multinucleated and show reduced furrow myosin II. A core biological role.
Reason: Directly supported; loss of PTEN causes cytokinesis failure and multinucleation.
Supporting Evidence:
PMID:19515202
PTEN knockout (pten(-)) cells became multinucleated, and myosin II significantly decreased in amount at the furrow
|
|
GO:0034461
uropod retraction
|
IMP
PMID:19515202 PTEN is a mechanosensing signal transducer for myosin II loc... |
KEEP AS NON CORE |
Summary: PTEN accumulates at retracting pseudopods/aspirated lobes prior to myosin II, acting upstream in tail (uropod) retraction.
Reason: Supported downstream contractile process dependent on PTEN-mediated myosin II localization; non-core.
Supporting Evidence:
PMID:19515202
During pseudopod retraction and cell aspiration by microcapillary, PTEN accumulated at the tips of pseudopods and aspirated lobes prior to the accumulation of myosin II
|
|
GO:0048870
cell motility
|
IMP
PMID:17623773 PTEN plays a role in the suppression of lateral pseudopod fo... |
KEEP AS NON CORE |
Summary: PTEN contributes to efficient motility by suppressing lateral pseudopods; pten- cells are less efficient in locomotion.
Reason: General motility term; the informative core roles are chemotaxis and pseudopod suppression. Non-core.
Supporting Evidence:
PMID:17623773
the fundamental incapacity of pten(-) cells to suppress lateral pseudopod formation and turning
|
|
GO:0048870
cell motility
|
IGI
PMID:17462897 Chemotaxis in the absence of PIP3 gradients. |
KEEP AS NON CORE |
Summary: In a PI3K1-5/PTEN sextuple mutant, chemotaxis is near-normal but there is a consistent defect in movement speed, implicating PTEN/PIP3 in motility efficiency rather than directional sensing.
Reason: Genetic-interaction evidence links PTEN to movement speed; a general motility contribution, non-core.
Supporting Evidence:
PMID:17462897
There is, however, a consistent defect in movement speed in chemotaxis and especially in random movement
|
|
GO:0031152
aggregation involved in sorocarp development
|
IMP
PMID:25247494 PTEN redundancy: overexpressing lpten, a homolog of Dictyost... |
KEEP AS NON CORE |
Summary: Deletion of ptenA impairs aggregation and multicellular morphogenesis; these developmental defects are rescuable by the homolog lpten.
Reason: Downstream developmental phenotype secondary to chemotaxis/polarity defects; non-core.
Supporting Evidence:
PMID:25247494
Deletion of ptenA results in defects in motility, chemotaxis, aggregation and multicellular morphogenesis
|
|
GO:0036051
protein localization to trailing edge
|
IDA
PMID:21169559 Disruption of PKB signaling restores polarity to cells lacki... |
KEEP AS NON CORE |
Summary: PTEN, itself a rear/trailing-edge protein, contributes to localizing cytoskeletal/PKB-substrate components to the trailing edge.
Reason: Downstream localization role tied to PTEN's rear positioning; non-core.
Supporting Evidence:
PMID:21169559
tumor suppressor PTEN not only controls cell growth but also maintains cell polarity required for cytokinesis and chemotaxis
|
|
GO:0000281
mitotic cytokinesis
|
IMP
PMID:21169559 Disruption of PKB signaling restores polarity to cells lacki... |
ACCEPT |
Summary: PTEN maintains the polarity required for cytokinesis; loss causes cytokinesis defects that are suppressed by disrupting downstream PKB signaling.
Reason: Directly supported role in cytokinesis via PIP3/PKB control.
Supporting Evidence:
PMID:21169559
tumor suppressor PTEN not only controls cell growth but also maintains cell polarity required for cytokinesis and chemotaxis
|
|
GO:0043327
chemotaxis to cAMP
|
IMP
PMID:21169559 Disruption of PKB signaling restores polarity to cells lacki... |
ACCEPT |
Summary: PTEN is required for efficient cAMP chemotaxis; pten- cells are poorly polarized and move slowly on circuitous routes, a defect suppressed by reducing PKB signaling.
Reason: Strongly supported core role in directed migration toward cAMP.
Supporting Evidence:
PMID:21169559
tumor suppressor PTEN not only controls cell growth but also maintains cell polarity required for cytokinesis and chemotaxis
|
|
GO:0022604
regulation of cell morphogenesis
|
IMP
PMID:19011688 Ordered patterns of cell shape and orientational correlation... |
KEEP AS NON CORE |
Summary: PTEN (with PI3K and F-actin) shapes the ordered patterns of cell deformation during migration by restricting excess pseudopods.
Reason: General cell-shape regulation downstream of PIP3 control; non-core.
Supporting Evidence:
PMID:19011688
phosphatase and tensin homolog, (PTEN), is simultaneously localized at the rear
|
|
GO:0031272
regulation of pseudopodium assembly
|
IMP
PMID:19011688 Ordered patterns of cell shape and orientational correlation... |
KEEP AS NON CORE |
Summary: PTEN restricts the formation of excess pseudopodia during spontaneous migration, regulating pseudopod assembly.
Reason: Downstream morphogenetic regulation; the negative-regulation aspect is the core function. Non-core here.
Supporting Evidence:
PMID:19011688
phosphatase and tensin homolog, (PTEN), is simultaneously localized at the rear
|
|
GO:0006935
chemotaxis
|
IMP
PMID:17623773 PTEN plays a role in the suppression of lateral pseudopod fo... |
KEEP AS NON CORE |
Summary: PTEN contributes to chemotaxis efficiency by suppressing lateral pseudopods; the more specific chemotaxis-to-cAMP term captures the core role.
Reason: General chemotaxis parent term; the specific cAMP chemotaxis annotation is the informative core term.
Supporting Evidence:
PMID:17623773
the fundamental incapacity of pten(-) cells to suppress lateral pseudopod formation and turning
|
|
GO:0007188
adenylate cyclase-modulating G protein-coupled receptor signaling pathway
|
IDA
PMID:17606871 Locally controlled inhibitory mechanisms are involved in euk... |
KEEP AS NON CORE |
Summary: PTEN participates in cAR1/GPCR chemosensing dynamics; its membrane distribution tracks receptor/G-protein activation and returns to baseline upon stimulus withdrawal.
Reason: Involvement in the cAMP GPCR signaling response is genuine but a specialized signaling context, not the core molecular function.
Supporting Evidence:
PMID:17606871
the return of the PIP3 phosphatase PTEN and PHCrac-GFP to their pre-stimulus distribution
|
|
GO:0050919
negative chemotaxis
|
IMP
PMID:17517960 Chemoattractants and chemorepellents act by inducing opposit... |
KEEP AS NON CORE |
Summary: During chemorepulsion the polarity of PI3K and PTEN is reversed relative to chemoattraction, with PTEN at the front, contributing to movement away from the source.
Reason: Supported role in chemorepulsion/negative chemotaxis; a specialized directional context, non-core.
Supporting Evidence:
PMID:17517960
In 8CPT-cAMP gradients, the localization of PI3K and PTEN is reversed compared with cAMP gradients
|
|
GO:0031254
cell trailing edge
|
IDA
PMID:16900100 Imaging of cell migration. |
ACCEPT |
Summary: PTEN is a rear/trailing-edge signaling component in migrating Dictyostelium cells. This review-derived localization is corroborated by primary imaging studies showing PTEN at the cell rear.
Reason: Trailing-edge localization of PTEN is well established by direct imaging in primary studies; retained as a valid localization.
Supporting Evidence:
PMID:19011688
phosphatase and tensin homolog, (PTEN), is simultaneously localized at the rear
|
id: Q8T9S7
gene_symbol: pten
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:44689
label: Dictyostelium discoideum
description: pten (ptenA) is the Dictyostelium discoideum ortholog of the tumor
suppressor PTEN, a phosphoinositide 3-phosphatase that removes the phosphate at
the D3 position of the inositol ring of phosphatidylinositol 3,4,5-trisphosphate
(PtdIns(3,4,5)P3/PIP3), regenerating PtdIns(4,5)P2 and thereby acting as the direct
antagonist of PI3-kinase. The protein has an N-terminal tensin-type phosphatase
domain and a C-terminal C2 domain; in vitro it also displays dual-specificity
protein phosphatase activity and soluble inositol-polyphosphate 3-phosphatase
activity, but its physiologically dominant activity is lipid PIP3 phosphatase.
PTEN is a peripheral membrane protein that binds PtdIns(4,5)P2 via an N-terminal
basic motif; in chemotaxing cells it is enriched on the plasma membrane of the
lateral sides and rear (uropod/trailing edge) and is depleted from the leading
edge, showing a distribution reciprocal to PI3-kinase. By restricting PIP3 to the
anterior, PTEN establishes and maintains front-rear polarity, suppresses lateral
pseudopod formation, and enables efficient chemotaxis toward cAMP. It also
localizes to the cleavage furrow and equatorial cortex during division, where it
contributes to cortical myosin II accumulation and cytokinesis, and participates
in chemorepulsion, bleb regulation, and density-dependent control of
proliferation. Loss of PTEN elevates PIP3 and PKB/Akt (PkbA) substrate
phosphorylation, causing broadened PIP3 responses, excess pseudopods, impaired
chemotaxis, multinucleation, and aggregation defects.
existing_annotations:
- term:
id: GO:0016314
label: phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: Phylogenetic inference of PIP3 3-phosphatase activity is the defining
and experimentally corroborated core molecular function of PTEN in
Dictyostelium.
action: ACCEPT
reason: The lipid phosphatase activity of PTEN toward PIP3 is well established
and is the physiologically dominant activity of this enzyme, directly
antagonizing PI3-kinase during chemotaxis.
supported_by:
- reference_id: PMID:14764604
supporting_text: the lipid phosphatase activity of PTEN mediates chemotaxis
and that the sharp localization of PI(3,4,5)P3 requires localization of PTEN
to the rear of the cell
- term:
id: GO:0051726
label: regulation of cell cycle
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: This IBA transfer from the PTEN/tensin family reflects the mammalian
tumor-suppressor role in cell-cycle control. In Dictyostelium the documented
cell-division phenotype is a cytokinesis (multinucleation) defect, not
regulation of cell-cycle progression per se.
action: MARK_AS_OVER_ANNOTATED
propagation_review:
root_cause: PROPAGATION_BAD
failure_modes:
- FUNCTIONAL_DIVERGENCE
source_entities:
- source_id: PANTHER:PTN000959472
source_label: "PANTHER node for the PTEN/tensin phosphatase family"
source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
comment: "Cell-cycle regulation reflects the mammalian tumor-suppressor role of PTEN; Dictyostelium PTEN acts as a PIP3 phosphatase in chemotaxis with no evidence of cell-cycle control"
- source_id: UniProtKB:P60484
source_label: "human PTEN"
source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
comment: "Mammalian PTEN regulates the cell cycle as a tumor suppressor; this role has diverged and is unsupported in Dictyostelium"
reason: There is no direct evidence that Dictyostelium PTEN regulates cell-cycle
progression; the observed division phenotype is failed cytokinesis, which is
captured more precisely by GO:0000281 mitotic cytokinesis. The general
cell-cycle term is an over-propagation from mammalian orthologs.
supported_by:
- reference_id: PMID:19515202
supporting_text: PTEN knockout (pten(-)) cells became multinucleated, and
myosin II significantly decreased in amount at the furrow
- term:
id: GO:0005634
label: nucleus
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: Nuclear localization is inferred phylogenetically from mammalian PTEN,
which has documented nuclear tumor-suppressor functions. Dictyostelium PTEN is
consistently reported as a peripheral plasma-membrane, cortical and cytosolic
protein, with no evidence of nuclear localization or function.
action: REMOVE
propagation_review:
root_cause: PROPAGATION_BAD
failure_modes:
- COMPARTMENT_OR_COMPLEX_MISMATCH
source_entities:
- source_id: PANTHER:PTN000959472
source_label: "PANTHER node for the PTEN/tensin phosphatase family"
source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
comment: "Nuclear localization derives from mammalian PTEN; all experimental Dictyostelium PTEN localization is plasma-membrane and cytosolic"
- source_id: UniProtKB:P60484
source_label: "human PTEN"
source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
comment: "Mammalian PTEN has a documented nuclear pool; Dictyostelium PTEN does not localize to the nucleus"
reason: This is an IBA over-propagation. All experimental localization data for
Dictyostelium PTEN place it at the plasma membrane (rear/lateral),
cortex/furrow, and cytosol; none support nuclear localization. The nuclear
role is a mammal-specific attribute that does not transfer to this ortholog.
supported_by:
- reference_id: PMID:12062103
supporting_text: Exogenously expressed PTEN-GFP localized to the surface
membrane at the rear of the cell
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: Plasma membrane localization is strongly supported by direct evidence;
PTEN is a peripheral membrane protein enriched at the rear and lateral sides
of chemotaxing cells.
action: ACCEPT
reason: PTEN functions as a peripheral membrane phosphatase acting on membrane
PIP3, and its rear/lateral plasma-membrane localization is directly observed.
supported_by:
- reference_id: PMID:12062103
supporting_text: Exogenously expressed PTEN-GFP localized to the surface
membrane at the rear of the cell
- term:
id: GO:0051896
label: regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: PTEN regulates PI3K/PKB signaling by degrading PIP3. The direction is
negative (see GO:0051898), but this general regulation term is not incorrect.
action: ACCEPT
reason: By dephosphorylating PIP3, PTEN is a bona fide regulator of the PI3K/PKB
(PkbA) pathway; loss of PTEN elevates and prolongs PKB substrate
phosphorylation.
supported_by:
- reference_id: PMID:21169559
supporting_text: The polarity defects in pten- cells correlate with elevated
phosphorylations of PKB substrates
- term:
id: GO:0005829
label: cytosol
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: A cytosolic pool of PTEN exists and is directly observed; PTEN
redistributes between the plasma membrane and the cytosol during signaling.
action: ACCEPT
reason: PTEN cycles on and off the membrane and has a genuine cytosolic pool,
supported by direct imaging and consistent with its soluble
inositol-phosphatase activity.
supported_by:
- reference_id: PMID:23132928
supporting_text: redistribution of PTEN to the cytosol
- term:
id: GO:0004725
label: protein tyrosine phosphatase activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: Protein tyrosine (dual-specificity) phosphatase activity is a
family-level attribute inherited from the PTEN/tensin catalytic fold. It is a
biochemical capability of PTEN but is not the physiologically dominant
activity, which is lipid PIP3 phosphatase.
action: KEEP_AS_NON_CORE
reason: The PTEN active site can dephosphorylate phosphotyrosine in vitro, but
no protein-phosphatase substrate or physiological role has been demonstrated
for Dictyostelium PTEN. Retain as a non-core catalytic capability.
- term:
id: GO:0004722
label: protein serine/threonine phosphatase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: enables
review:
summary: Serine/threonine (dual-specificity) protein phosphatase activity
derives from EC 3.1.3.16 mapping to the PTEN catalytic domain. It is a
possible in-vitro capability but not a demonstrated physiological function.
action: KEEP_AS_NON_CORE
reason: PTEN is a dual-specificity phosphatase by similarity, but its
dominant physiological role is lipid PIP3 dephosphorylation; no protein
ser/thr substrate is documented in Dictyostelium.
- term:
id: GO:0004725
label: protein tyrosine phosphatase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: enables
review:
summary: Duplicate protein tyrosine phosphatase assignment from automated EC
mapping; same rationale as the IBA protein tyrosine phosphatase annotation.
action: KEEP_AS_NON_CORE
reason: A biochemical capability of the PTEN fold, not the core physiological
activity in Dictyostelium.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: General cytoplasmic localization from UniProt subcellular-location
mapping; consistent with PTEN's cytosolic and cortical pools.
action: ACCEPT
reason: PTEN is a cytoplasmic (peripheral membrane/cytosolic) protein, directly
supported by imaging.
supported_by:
- reference_id: PMID:23132928
supporting_text: redistribution of PTEN to the cytosol
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: Plasma membrane localization from UniProt mapping, strongly corroborated
by direct imaging of PTEN-GFP at the rear membrane.
action: ACCEPT
reason: PTEN is a peripheral plasma-membrane protein acting on membrane PIP3.
supported_by:
- reference_id: PMID:12062103
supporting_text: Exogenously expressed PTEN-GFP localized to the surface
membrane at the rear of the cell
- term:
id: GO:0005938
label: cell cortex
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: Cortical localization from UniProt mapping; PTEN is constitutively
localized in the cortex of polarized cells.
action: ACCEPT
reason: Directly supported experimental cortical localization in polarized
cells.
supported_by:
- reference_id: PMID:17623773
supporting_text: PTEN, which is constitutively localized in the cortex of
polarized cells
- term:
id: GO:0016314
label: phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: enables
review:
summary: Automated assignment of the core PIP3 3-phosphatase activity; redundant
with and consistent with the IBA/ISS/experimental support.
action: ACCEPT
reason: This is the defining core molecular function of PTEN.
supported_by:
- reference_id: PMID:14764604
supporting_text: the lipid phosphatase activity of PTEN mediates chemotaxis
- term:
id: GO:0016791
label: phosphatase activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: Grandparent-level generic phosphatase term from InterPro2GO. Not
incorrect, but uninformative given the specific PIP3 3-phosphatase activity is
annotated.
action: KEEP_AS_NON_CORE
reason: The specific term GO:0016314 (PIP3 3-phosphatase activity) captures the
core function; the generic phosphatase term is redundant and low-information.
- term:
id: GO:0030351
label: inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity
evidence_type: IEA
original_reference_id: GO_REF:0000116
qualifier: enables
review:
summary: Soluble inositol-polyphosphate 3-phosphatase activity toward
Ins(1,3,4,5,6)P5, assigned by Rhea mapping and by similarity to human PTEN.
Plausible but not experimentally demonstrated in Dictyostelium.
action: KEEP_AS_NON_CORE
reason: PTEN can act as a cytosolic inositol 3-phosphatase by similarity, but
this is a secondary activity relative to its core lipid PIP3 phosphatase role.
- term:
id: GO:0031038
label: myosin II filament organization
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: PTEN promotes cortical/posterior myosin II accumulation, so involvement
in myosin II organization is supported, but this is a downstream consequence
of PIP3 regulation rather than a core molecular function.
action: KEEP_AS_NON_CORE
reason: PTEN acts upstream to localize myosin II; a genuine but downstream
process, not the core activity.
supported_by:
- reference_id: PMID:19515202
supporting_text: PTEN and myosin II co-localized at the posterior of migrating
cells and furrow region of dividing cells
- term:
id: GO:0031152
label: aggregation involved in sorocarp development
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: pten- cells fail to aggregate normally, so a developmental role in
aggregation is supported (also annotated by IMP), but this is a downstream
developmental phenotype, not a core molecular function.
action: KEEP_AS_NON_CORE
reason: Aggregation defects are a downstream consequence of impaired
chemotaxis/polarity; retain as non-core developmental role.
supported_by:
- reference_id: PMID:25247494
supporting_text: Deletion of ptenA results in defects in motility, chemotaxis,
aggregation and multicellular morphogenesis
- term:
id: GO:0046580
label: negative regulation of Ras protein signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: PTEN (with CnrN) locally inhibits Ras activation, supporting this
process; consistent with the IMP annotation from the same phenomenon.
action: KEEP_AS_NON_CORE
reason: Supported downstream process; PTEN restrains Ras activity, but this is a
pathway-level effect of PIP3 regulation rather than a core molecular activity.
supported_by:
- reference_id: PMID:38940195
supporting_text: require both PTEN and CnrN to locally inhibit Ras activation
- term:
id: GO:0050793
label: regulation of developmental process
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: Very general developmental regulation term inferred by ARBA; pten- has
developmental (aggregation/morphogenesis) defects but this term is too broad
to be informative.
action: KEEP_AS_NON_CORE
reason: More specific developmental terms (aggregation involved in sorocarp
development) capture the phenotype; this broad term is non-core.
supported_by:
- reference_id: PMID:25247494
supporting_text: Deletion of ptenA results in defects in motility, chemotaxis,
aggregation and multicellular morphogenesis
- term:
id: GO:0051489
label: regulation of filopodium assembly
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: PTEN influences filopod size/formation, supporting a role in filopodium
regulation, but as a downstream cytoskeletal effect of PIP3 control.
action: KEEP_AS_NON_CORE
reason: Downstream cytoskeletal regulation; retain as non-core.
supported_by:
- reference_id: PMID:38940195
supporting_text: AprA requires both PTEN and CnrN to increase PI(4,5)P2 levels,
decrease PI(3,4,5)P3 levels, inhibit proliferation, decrease myosin II
phosphorylation and increase filopod sizes
- term:
id: GO:0051717
label: inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
evidence_type: IEA
original_reference_id: GO_REF:0000116
qualifier: enables
review:
summary: Soluble inositol-phosphate 3-phosphatase activity toward Ins(1,3,4,5)P4,
assigned by Rhea mapping and by similarity. Plausible secondary activity, not
demonstrated in Dictyostelium.
action: KEEP_AS_NON_CORE
reason: Secondary soluble inositol-phosphatase capability by similarity; not the
core lipid phosphatase function.
- term:
id: GO:0051898
label: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal
transduction
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: PTEN negatively regulates PI3K/PKB signaling by degrading PIP3; this is
a core biological role, also supported by IMP.
action: ACCEPT
reason: Loss of PTEN elevates and prolongs PKB (PkbA) substrate phosphorylation,
directly demonstrating negative regulation of this pathway.
supported_by:
- reference_id: PMID:21169559
supporting_text: The polarity defects in pten- cells correlate with elevated
phosphorylations of PKB substrates
- term:
id: GO:0052866
label: phosphatidylinositol phosphate phosphatase activity
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: enables
review:
summary: General phosphatidylinositol-phosphate phosphatase term; a parent of
the specific PIP3 3-phosphatase activity.
action: KEEP_AS_NON_CORE
reason: The specific PIP3 3-phosphatase term is the informative core function;
this parent term is redundant.
- term:
id: GO:0140986
label: G protein-coupled chemorepellent receptor signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: PTEN is required for AprA-induced chemorepulsion, supporting
involvement in chemorepellent GPCR signaling (also annotated by IMP).
action: KEEP_AS_NON_CORE
reason: Genuine but specialized downstream signaling role; not the core
molecular function.
supported_by:
- reference_id: PMID:38940195
supporting_text: Dictyostelium discoideum cells require both PTEN and CnrN to
induce chemorepulsion of cells away from the secreted chemorepellent protein
AprA
- term:
id: GO:1903665
label: negative regulation of asexual reproduction
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: PTEN participates in density/polyphosphate-dependent proliferation
inhibition, supporting negative regulation of asexual reproduction
(proliferation), also annotated by IMP.
action: KEEP_AS_NON_CORE
reason: Supported downstream role in proliferation control; not a core molecular
activity.
supported_by:
- reference_id: PMID:34154396
supporting_text: Polyphosphate upregulates IP3, and this requires GrlD, GefA,
PTEN, PLC, and PiaA
- term:
id: GO:0004722
label: protein serine/threonine phosphatase activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: enables
review:
summary: Serine/threonine protein phosphatase activity transferred by sequence
similarity from human PTEN. A dual-specificity capability, not the core role.
action: KEEP_AS_NON_CORE
reason: Biochemical capability by similarity; the physiological function is
lipid PIP3 dephosphorylation.
- term:
id: GO:0004725
label: protein tyrosine phosphatase activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: enables
review:
summary: Protein tyrosine phosphatase activity transferred by similarity from
human PTEN; a capability of the PTEN fold, not the dominant activity.
action: KEEP_AS_NON_CORE
reason: Non-core dual-specificity capability by similarity.
- term:
id: GO:0016314
label: phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: enables
review:
summary: Core PIP3 3-phosphatase activity transferred by sequence similarity from
human PTEN and corroborated experimentally in Dictyostelium.
action: ACCEPT
reason: This is the defining core molecular function of PTEN.
supported_by:
- reference_id: PMID:14764604
supporting_text: the lipid phosphatase activity of PTEN mediates chemotaxis
- term:
id: GO:0030351
label: inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: enables
review:
summary: Soluble Ins(1,3,4,5,6)P5 3-phosphatase activity by similarity; a
plausible secondary activity.
action: KEEP_AS_NON_CORE
reason: Secondary soluble inositol-phosphatase capability, not the core lipid
phosphatase function.
- term:
id: GO:0051717
label: inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: enables
review:
summary: Soluble Ins(1,3,4,5)P4 3-phosphatase activity by similarity; a plausible
secondary activity.
action: KEEP_AS_NON_CORE
reason: Secondary soluble inositol-phosphatase capability, not the core function.
- term:
id: GO:0031273
label: negative regulation of pseudopodium assembly
evidence_type: IMP
original_reference_id: PMID:38940195
qualifier: acts_upstream_of_or_within
review:
summary: Suppression of pseudopod formation is a hallmark PTEN function; by
degrading PIP3 at the sides and rear, PTEN restrains lateral pseudopod
assembly, which is central to directed migration and chemorepulsion.
action: ACCEPT
reason: A well-supported core biological role of PTEN; pten- cells cannot suppress
lateral pseudopods, and PTEN is required for AprA-induced pseudopod inhibition.
supported_by:
- reference_id: PMID:17623773
supporting_text: PTEN, therefore, plays a fundamental role in the suppression
of lateral pseudopod formation
- term:
id: GO:0051490
label: negative regulation of filopodium assembly
evidence_type: IMP
original_reference_id: PMID:38940195
qualifier: acts_upstream_of_or_within
review:
summary: PTEN affects filopod size/number in the AprA chemorepulsion pathway;
supported downstream cytoskeletal regulation.
action: KEEP_AS_NON_CORE
reason: Genuine but downstream cytoskeletal effect of PIP3 control; non-core.
supported_by:
- reference_id: PMID:38940195
supporting_text: AprA requires both PTEN and CnrN to increase PI(4,5)P2 levels,
decrease PI(3,4,5)P3 levels, inhibit proliferation, decrease myosin II
phosphorylation and increase filopod sizes
- term:
id: GO:0046580
label: negative regulation of Ras protein signal transduction
evidence_type: IMP
original_reference_id: PMID:38940195
qualifier: acts_upstream_of_or_within
review:
summary: PTEN (together with CnrN) is required to locally inhibit Ras activation,
a genuine signaling role demonstrated by mutant analysis, though it is a
downstream pathway effect rather than the core molecular function.
action: KEEP_AS_NON_CORE
reason: 'Experimentally supported: pten- cells fail to locally inhibit Ras
activation, linking PTEN to negative regulation of Ras signaling; this is a
downstream signaling consequence of PIP3 restriction, kept consistent with the
IEA annotation to the same term.'
supported_by:
- reference_id: PMID:38940195
supporting_text: require both PTEN and CnrN to locally inhibit Ras activation
- term:
id: GO:0031038
label: myosin II filament organization
evidence_type: IMP
original_reference_id: PMID:38940195
qualifier: acts_upstream_of_or_within
review:
summary: PTEN influences myosin II phosphorylation/organization; a downstream
cytoskeletal consequence of PIP3 regulation.
action: KEEP_AS_NON_CORE
reason: Supported downstream role in myosin II regulation; not a core molecular
activity.
supported_by:
- reference_id: PMID:38940195
supporting_text: AprA requires both PTEN and CnrN to increase PI(4,5)P2 levels,
decrease PI(3,4,5)P3 levels, inhibit proliferation, decrease myosin II
phosphorylation and increase filopod sizes
- term:
id: GO:1903665
label: negative regulation of asexual reproduction
evidence_type: IMP
original_reference_id: PMID:38940195
qualifier: acts_upstream_of_or_within
review:
summary: PTEN is required for AprA-mediated inhibition of proliferation, linking
it to negative regulation of asexual reproduction.
action: KEEP_AS_NON_CORE
reason: Supported downstream role in proliferation control; non-core.
supported_by:
- reference_id: PMID:38940195
supporting_text: AprA requires both PTEN and CnrN to increase PI(4,5)P2 levels,
decrease PI(3,4,5)P3 levels, inhibit proliferation, decrease myosin II
phosphorylation and increase filopod sizes
- term:
id: GO:0051898
label: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal
transduction
evidence_type: IMP
original_reference_id: PMID:21169559
qualifier: involved_in
review:
summary: Directly supported core role; disruption of PTEN elevates and prolongs
PKB (PkbA) substrate phosphorylation, and the polarity defects track with this
hyperphosphorylation.
action: ACCEPT
reason: Strong experimental support for PTEN as a negative regulator of the
PI3K/PKB pathway in Dictyostelium.
supported_by:
- reference_id: PMID:21169559
supporting_text: The polarity defects in pten- cells correlate with elevated
phosphorylations of PKB substrates
- term:
id: GO:0051896
label: regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: IMP
original_reference_id: PMID:20562345
qualifier: involved_in
review:
summary: PTEN, with PI3K, regulates the spatiotemporal dynamics of PtdIns lipids
and is essential for self-organized PIP3 waves underlying migration.
action: ACCEPT
reason: Experimentally supported regulatory role in the PI3K/PIP3 signaling
system; PTEN is essential for the lipid wave dynamics.
supported_by:
- reference_id: PMID:20562345
supporting_text: regulators for PtdIns lipid concentrations along the membrane,
were essential for wave generation
- term:
id: GO:0001931
label: uropod
evidence_type: IDA
original_reference_id: PMID:19515202
qualifier: is_active_in
review:
summary: PTEN localizes to the posterior (uropod) of migrating cells, directly
observed by fluorescence imaging, consistent with its rear-restricted role.
action: ACCEPT
reason: Direct imaging places PTEN at the posterior/uropod of migrating cells.
supported_by:
- reference_id: PMID:19515202
supporting_text: PTEN and myosin II co-localized at the posterior of migrating
cells and furrow region of dividing cells
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: PMID:15473840
qualifier: located_in
review:
summary: A cytosolic pool of PTEN is described; PTEN cycles between the plasma
membrane and cytosol during chemoattractant signaling.
action: ACCEPT
reason: Consistent with directly observed cytosolic redistribution of PTEN.
supported_by:
- reference_id: PMID:23132928
supporting_text: redistribution of PTEN to the cytosol
- term:
id: GO:0031254
label: cell trailing edge
evidence_type: IDA
original_reference_id: PMID:19011688
qualifier: is_active_in
review:
summary: PTEN is directly observed to localize at the rear/trailing edge of
spontaneously migrating cells, where it restricts excess pseudopod formation.
action: ACCEPT
reason: Direct imaging localizes PTEN to the cell rear/trailing edge.
supported_by:
- reference_id: PMID:19011688
supporting_text: phosphatase and tensin homolog, (PTEN), is simultaneously
localized at the rear
- term:
id: GO:0031257
label: cell trailing edge membrane
evidence_type: IDA
original_reference_id: PMID:12062104
qualifier: is_active_in
review:
summary: PTEN shows a distribution reciprocal to PI3K, occupying the plasma
membrane along the lateral sides and posterior of chemotaxing cells.
action: ACCEPT
reason: Directly supported rear-membrane localization; PTEN's reciprocal
distribution to PI3K places it on the trailing-edge membrane.
supported_by:
- reference_id: PMID:12062104
supporting_text: PTEN, a negative regulator of PI3K pathways, exhibits a
reciprocal pattern of localization
- term:
id: GO:0032154
label: cleavage furrow
evidence_type: IDA
original_reference_id: PMID:19515202
qualifier: is_active_in
review:
summary: PTEN localizes to the furrow region of dividing cells, directly observed
together with myosin II.
action: ACCEPT
reason: Direct imaging places PTEN at the cleavage furrow during cytokinesis.
supported_by:
- reference_id: PMID:19515202
supporting_text: PTEN and myosin II co-localized at the posterior of migrating
cells and furrow region of dividing cells
- term:
id: GO:0051285
label: cell cortex of cell tip
evidence_type: IDA
original_reference_id: PMID:17623773
qualifier: is_active_in
review:
summary: PTEN is constitutively localized in the cortex of polarized cells,
including at cell tips/pseudopod-suppressing cortical regions.
action: ACCEPT
reason: Directly supported constitutive cortical localization in polarized cells.
supported_by:
- reference_id: PMID:17623773
supporting_text: PTEN, which is constitutively localized in the cortex of
polarized cells
- term:
id: GO:1990753
label: equatorial cell cortex
evidence_type: IDA
original_reference_id: PMID:19515202
qualifier: is_active_in
review:
summary: During division PTEN accumulates at the equatorial/furrow cortex, where
it contributes to myosin II accumulation and cytokinesis.
action: ACCEPT
reason: Direct imaging localizes PTEN to the equatorial cortex/furrow of dividing
cells.
supported_by:
- reference_id: PMID:19515202
supporting_text: PTEN and myosin II co-localized at the posterior of migrating
cells and furrow region of dividing cells
- term:
id: GO:0140986
label: G protein-coupled chemorepellent receptor signaling pathway
evidence_type: IMP
original_reference_id: PMID:30462573
qualifier: acts_upstream_of_or_within
review:
summary: PTEN localizes myosin II to the rear during chemorepulsion; it is part
of the AprA chemorepellent GPCR signaling response.
action: KEEP_AS_NON_CORE
reason: Genuine but specialized downstream signaling role in chemorepulsion.
supported_by:
- reference_id: PMID:30462573
supporting_text: PTEN to localize myosin II to the rear of a cell
- term:
id: GO:0030010
label: establishment of cell polarity
evidence_type: IMP
original_reference_id: PMID:21169559
qualifier: involved_in
review:
summary: By restricting PIP3, PTEN establishes and maintains front-rear polarity
required for cytokinesis and chemotaxis; a core biological role.
action: ACCEPT
reason: Strongly supported; loss of PTEN causes loss of polarity, and PTEN is
required to maintain the polarity underlying directed migration and division.
supported_by:
- reference_id: PMID:21169559
supporting_text: tumor suppressor PTEN not only controls cell growth but also
maintains cell polarity required for cytokinesis and chemotaxis
- term:
id: GO:0036052
label: protein localization to uropod
evidence_type: IMP
original_reference_id: PMID:19515202
qualifier: involved_in
review:
summary: PTEN acts upstream to recruit/localize myosin II to the posterior
(uropod), accumulating there prior to myosin II.
action: KEEP_AS_NON_CORE
reason: Downstream effect of PTEN's rear localization and PIP3 restriction; not
the core molecular activity.
supported_by:
- reference_id: PMID:19515202
supporting_text: During pseudopod retraction and cell aspiration by
microcapillary, PTEN accumulated at the tips of pseudopods and aspirated
lobes prior to the accumulation of myosin II
- term:
id: GO:0080025
label: phosphatidylinositol-3,5-bisphosphate binding
evidence_type: IDA
original_reference_id: PMID:35186938
qualifier: enables
review:
summary: In vitro, PTEN preferentially bound liposomes containing PI(4,5)P2 and
PI(3,5)P2, indicating PI(3,5)P2 binding capacity that may contribute to back
(rear) membrane localization.
action: KEEP_AS_NON_CORE
reason: Directly demonstrated lipid-binding property that supports membrane
targeting to the back, but distinct from the core catalytic function.
supported_by:
- reference_id: PMID:35186938
supporting_text: Pten preferentially bound to liposomes containing PI(4,5)P2
and PI(3,5)P2
- term:
id: GO:0005829
label: cytosol
evidence_type: IDA
original_reference_id: PMID:23132928
qualifier: located_in
review:
summary: Direct imaging shows PTEN redistributing to the cytosol upon stimulation
and residing in the cytoplasm when membrane PI(4,5)P2 is depleted.
action: ACCEPT
reason: Directly supported cytosolic pool of PTEN.
supported_by:
- reference_id: PMID:23132928
supporting_text: redistribution of PTEN to the cytosol
- term:
id: GO:1903665
label: negative regulation of asexual reproduction
evidence_type: IMP
original_reference_id: PMID:34154396
qualifier: acts_upstream_of_or_within
review:
summary: PTEN is required for polyphosphate-mediated inhibition of proliferation,
acting within a density-sensing autocrine feedback loop.
action: KEEP_AS_NON_CORE
reason: Supported downstream role in density-dependent proliferation control;
non-core.
supported_by:
- reference_id: PMID:34154396
supporting_text: Polyphosphate upregulates IP3, and this requires GrlD, GefA,
PTEN, PLC, and PiaA
- term:
id: GO:0032060
label: bleb assembly
evidence_type: IMP
original_reference_id: PMID:26317626
qualifier: acts_upstream_of_or_within
review:
summary: PTEN-null cells extend fewer blebs, implicating PTEN in bleb regulation
via inositol lipid metabolism.
action: KEEP_AS_NON_CORE
reason: Supported downstream role in blebbing through PIP3/PIP2 balance; not the
core molecular activity.
supported_by:
- reference_id: PMID:26317626
supporting_text: PTEN-null cells extended fewer blebs
- term:
id: GO:0005546
label: phosphatidylinositol-4,5-bisphosphate binding
evidence_type: IDA
original_reference_id: PMID:32111929
qualifier: enables
review:
summary: PTEN binds its enzymatic product PI(4,5)P2, which stabilizes its
membrane binding in a basic-residue-dependent, positive-feedback manner and
drives its posterior accumulation.
action: ACCEPT
reason: Directly demonstrated PI(4,5)P2 binding is central to PTEN's rear
membrane targeting mechanism and to restricting PIP3 to the anterior.
supported_by:
- reference_id: PMID:32111929
supporting_text: the enzymatic product, PI(4,5)P2, stabilizes PTEN's
membrane-binding
- term:
id: GO:0034485
label: phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity
evidence_type: IDA
original_reference_id: PMID:14764604
qualifier: enables
review:
summary: This annotation assigns 5-phosphatase activity (the reaction catalyzed
by SHIP-type enzymes, yielding PI(3,4)P2), which conflicts with PTEN's
well-established mechanism as a D3 (3-position) phosphatase. The cited abstract
does not describe 5-phosphatase activity and the full text is not available to
verify the experimental basis.
action: UNDECIDED
reason: PTEN is defined mechanistically as a PIP3 3-phosphatase; a 5-phosphatase
activity is inconsistent with this. As the relevant full text cannot be
accessed to confirm the assay, this is flagged UNDECIDED rather than removed,
per policy on unverifiable experimental annotations.
- term:
id: GO:0051800
label: phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
evidence_type: IDA
original_reference_id: PMID:14764604
qualifier: enables
review:
summary: PTEN also dephosphorylates PtdIns(3,4)P2 at the 3-position, consistent
with its D3 phosphatase mechanism and with UniProt substrate annotation. This
is a genuine but secondary activity relative to the preferred PIP3 substrate.
action: KEEP_AS_NON_CORE
reason: PI(3,4)P2 is a documented secondary substrate of PTEN; the core activity
is PIP3 3-phosphatase, so this is retained as non-core.
- term:
id: GO:0043491
label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: IMP
original_reference_id: PMID:12062104
qualifier: acts_upstream_of_or_within
review:
summary: PTEN acts within the PI3K/PKB pathway; disruption prolongs and broadens
PIP3-dependent (PH-domain) responses. The negative-regulation aspect is better
captured by GO:0051898.
action: KEEP_AS_NON_CORE
reason: PTEN acts upstream within this pathway as its negative regulator; the
specific negative-regulation term is the more informative core annotation.
supported_by:
- reference_id: PMID:12062103
supporting_text: Disruption of the PI 3-phosphatase, PTEN, in Dictyostelium
discoideum dramatically prolonged and broadened the PH domain relocation and
actin polymerization responses
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:12062103
qualifier: located_in
review:
summary: PTEN-GFP directly localizes to the plasma membrane at the rear of the
cell; membrane localization requires the PI(4,5)P2-binding motif.
action: ACCEPT
reason: Directly observed plasma-membrane localization essential for function.
supported_by:
- reference_id: PMID:12062103
supporting_text: Exogenously expressed PTEN-GFP localized to the surface
membrane at the rear of the cell
- term:
id: GO:0030041
label: actin filament polymerization
evidence_type: IMP
original_reference_id: PMID:12062103
qualifier: acts_upstream_of_or_within
review:
summary: Loss of PTEN broadens and prolongs actin polymerization responses;
PTEN acts upstream of actin dynamics via PIP3 restriction rather than directly
polymerizing actin.
action: KEEP_AS_NON_CORE
reason: Downstream cytoskeletal consequence of PIP3 regulation; not a core
molecular activity.
supported_by:
- reference_id: PMID:12062103
supporting_text: Disruption of the PI 3-phosphatase, PTEN, in Dictyostelium
discoideum dramatically prolonged and broadened the PH domain relocation and
actin polymerization responses
- term:
id: GO:0031269
label: pseudopodium assembly
evidence_type: IMP
original_reference_id: PMID:12062103
qualifier: acts_upstream_of_or_within
review:
summary: PTEN regulates pseudopod formation; its normal role is to restrict
pseudopods to the front, and loss leads to broadened/excess pseudopod
responses.
action: KEEP_AS_NON_CORE
reason: Downstream morphogenetic process controlled via PIP3; the negative
regulation of pseudopodia is the more informative aspect. Non-core.
supported_by:
- reference_id: PMID:12062103
supporting_text: Disruption of the PI 3-phosphatase, PTEN, in Dictyostelium
discoideum dramatically prolonged and broadened the PH domain relocation and
actin polymerization responses
- term:
id: GO:0043327
label: chemotaxis to cAMP
evidence_type: IMP
original_reference_id: PMID:12062103
qualifier: acts_upstream_of_or_within
review:
summary: PTEN is required for efficient cAMP chemotaxis; pten- cells follow
circuitous routes toward the attractant. A core biological role.
action: ACCEPT
reason: Strongly supported; PTEN-mediated gradient sensing/polarity is required
for directional migration toward cAMP.
supported_by:
- reference_id: PMID:12062103
supporting_text: causing the cells lacking PTEN to follow a circuitous route
toward the attractant
- term:
id: GO:0000281
label: mitotic cytokinesis
evidence_type: IMP
original_reference_id: PMID:19515202
qualifier: acts_upstream_of_or_within
review:
summary: PTEN is required for cytokinesis; pten- cells become multinucleated and
show reduced furrow myosin II. A core biological role.
action: ACCEPT
reason: Directly supported; loss of PTEN causes cytokinesis failure and
multinucleation.
supported_by:
- reference_id: PMID:19515202
supporting_text: PTEN knockout (pten(-)) cells became multinucleated, and
myosin II significantly decreased in amount at the furrow
- term:
id: GO:0034461
label: uropod retraction
evidence_type: IMP
original_reference_id: PMID:19515202
qualifier: acts_upstream_of_or_within
review:
summary: PTEN accumulates at retracting pseudopods/aspirated lobes prior to
myosin II, acting upstream in tail (uropod) retraction.
action: KEEP_AS_NON_CORE
reason: Supported downstream contractile process dependent on PTEN-mediated
myosin II localization; non-core.
supported_by:
- reference_id: PMID:19515202
supporting_text: During pseudopod retraction and cell aspiration by
microcapillary, PTEN accumulated at the tips of pseudopods and aspirated
lobes prior to the accumulation of myosin II
- term:
id: GO:0048870
label: cell motility
evidence_type: IMP
original_reference_id: PMID:17623773
qualifier: acts_upstream_of_or_within
review:
summary: PTEN contributes to efficient motility by suppressing lateral
pseudopods; pten- cells are less efficient in locomotion.
action: KEEP_AS_NON_CORE
reason: General motility term; the informative core roles are chemotaxis and
pseudopod suppression. Non-core.
supported_by:
- reference_id: PMID:17623773
supporting_text: the fundamental incapacity of pten(-) cells to suppress
lateral pseudopod formation and turning
- term:
id: GO:0048870
label: cell motility
evidence_type: IGI
original_reference_id: PMID:17462897
qualifier: acts_upstream_of_or_within
review:
summary: In a PI3K1-5/PTEN sextuple mutant, chemotaxis is near-normal but there
is a consistent defect in movement speed, implicating PTEN/PIP3 in motility
efficiency rather than directional sensing.
action: KEEP_AS_NON_CORE
reason: Genetic-interaction evidence links PTEN to movement speed; a general
motility contribution, non-core.
supported_by:
- reference_id: PMID:17462897
supporting_text: There is, however, a consistent defect in movement speed in
chemotaxis and especially in random movement
- term:
id: GO:0031152
label: aggregation involved in sorocarp development
evidence_type: IMP
original_reference_id: PMID:25247494
qualifier: acts_upstream_of_or_within
review:
summary: Deletion of ptenA impairs aggregation and multicellular morphogenesis;
these developmental defects are rescuable by the homolog lpten.
action: KEEP_AS_NON_CORE
reason: Downstream developmental phenotype secondary to chemotaxis/polarity
defects; non-core.
supported_by:
- reference_id: PMID:25247494
supporting_text: Deletion of ptenA results in defects in motility, chemotaxis,
aggregation and multicellular morphogenesis
- term:
id: GO:0036051
label: protein localization to trailing edge
evidence_type: IDA
original_reference_id: PMID:21169559
qualifier: involved_in
review:
summary: PTEN, itself a rear/trailing-edge protein, contributes to localizing
cytoskeletal/PKB-substrate components to the trailing edge.
action: KEEP_AS_NON_CORE
reason: Downstream localization role tied to PTEN's rear positioning; non-core.
supported_by:
- reference_id: PMID:21169559
supporting_text: tumor suppressor PTEN not only controls cell growth but also
maintains cell polarity required for cytokinesis and chemotaxis
- term:
id: GO:0000281
label: mitotic cytokinesis
evidence_type: IMP
original_reference_id: PMID:21169559
qualifier: acts_upstream_of_or_within
review:
summary: PTEN maintains the polarity required for cytokinesis; loss causes
cytokinesis defects that are suppressed by disrupting downstream PKB signaling.
action: ACCEPT
reason: Directly supported role in cytokinesis via PIP3/PKB control.
supported_by:
- reference_id: PMID:21169559
supporting_text: tumor suppressor PTEN not only controls cell growth but also
maintains cell polarity required for cytokinesis and chemotaxis
- term:
id: GO:0043327
label: chemotaxis to cAMP
evidence_type: IMP
original_reference_id: PMID:21169559
qualifier: acts_upstream_of_or_within
review:
summary: PTEN is required for efficient cAMP chemotaxis; pten- cells are poorly
polarized and move slowly on circuitous routes, a defect suppressed by
reducing PKB signaling.
action: ACCEPT
reason: Strongly supported core role in directed migration toward cAMP.
supported_by:
- reference_id: PMID:21169559
supporting_text: tumor suppressor PTEN not only controls cell growth but also
maintains cell polarity required for cytokinesis and chemotaxis
- term:
id: GO:0022604
label: regulation of cell morphogenesis
evidence_type: IMP
original_reference_id: PMID:19011688
qualifier: acts_upstream_of_or_within
review:
summary: PTEN (with PI3K and F-actin) shapes the ordered patterns of cell
deformation during migration by restricting excess pseudopods.
action: KEEP_AS_NON_CORE
reason: General cell-shape regulation downstream of PIP3 control; non-core.
supported_by:
- reference_id: PMID:19011688
supporting_text: phosphatase and tensin homolog, (PTEN), is simultaneously
localized at the rear
- term:
id: GO:0031272
label: regulation of pseudopodium assembly
evidence_type: IMP
original_reference_id: PMID:19011688
qualifier: acts_upstream_of_or_within
review:
summary: PTEN restricts the formation of excess pseudopodia during spontaneous
migration, regulating pseudopod assembly.
action: KEEP_AS_NON_CORE
reason: Downstream morphogenetic regulation; the negative-regulation aspect is
the core function. Non-core here.
supported_by:
- reference_id: PMID:19011688
supporting_text: phosphatase and tensin homolog, (PTEN), is simultaneously
localized at the rear
- term:
id: GO:0006935
label: chemotaxis
evidence_type: IMP
original_reference_id: PMID:17623773
qualifier: acts_upstream_of_or_within
review:
summary: PTEN contributes to chemotaxis efficiency by suppressing lateral
pseudopods; the more specific chemotaxis-to-cAMP term captures the core role.
action: KEEP_AS_NON_CORE
reason: General chemotaxis parent term; the specific cAMP chemotaxis annotation
is the informative core term.
supported_by:
- reference_id: PMID:17623773
supporting_text: the fundamental incapacity of pten(-) cells to suppress
lateral pseudopod formation and turning
- term:
id: GO:0007188
label: adenylate cyclase-modulating G protein-coupled receptor signaling pathway
evidence_type: IDA
original_reference_id: PMID:17606871
qualifier: involved_in
review:
summary: PTEN participates in cAR1/GPCR chemosensing dynamics; its membrane
distribution tracks receptor/G-protein activation and returns to baseline upon
stimulus withdrawal.
action: KEEP_AS_NON_CORE
reason: Involvement in the cAMP GPCR signaling response is genuine but a
specialized signaling context, not the core molecular function.
supported_by:
- reference_id: PMID:17606871
supporting_text: the return of the PIP3 phosphatase PTEN and PHCrac-GFP to
their pre-stimulus distribution
- term:
id: GO:0050919
label: negative chemotaxis
evidence_type: IMP
original_reference_id: PMID:17517960
qualifier: acts_upstream_of_or_within
review:
summary: During chemorepulsion the polarity of PI3K and PTEN is reversed relative
to chemoattraction, with PTEN at the front, contributing to movement away from
the source.
action: KEEP_AS_NON_CORE
reason: Supported role in chemorepulsion/negative chemotaxis; a specialized
directional context, non-core.
supported_by:
- reference_id: PMID:17517960
supporting_text: In 8CPT-cAMP gradients, the localization of PI3K and PTEN is
reversed compared with cAMP gradients
- term:
id: GO:0031254
label: cell trailing edge
evidence_type: IDA
original_reference_id: PMID:16900100
qualifier: located_in
review:
summary: PTEN is a rear/trailing-edge signaling component in migrating
Dictyostelium cells. This review-derived localization is corroborated by
primary imaging studies showing PTEN at the cell rear.
action: ACCEPT
reason: Trailing-edge localization of PTEN is well established by direct imaging
in primary studies; retained as a valid localization.
supported_by:
- reference_id: PMID:19011688
supporting_text: phosphatase and tensin homolog, (PTEN), is simultaneously
localized at the rear
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO
terms
findings: []
- id: GO_REF:0000024
title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
by curator judgment of sequence similarity
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
vocabulary mapping, accompanied by conservative changes to GO terms applied by
UniProt
findings: []
- id: GO_REF:0000116
title: Automatic Gene Ontology annotation based on Rhea mapping
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:12062103
title: Tumor suppressor PTEN mediates sensing of chemoattractant gradients.
findings:
- statement: PTEN-GFP localizes to the plasma membrane at the rear of the cell,
and membrane localization requires a PI(4,5)P2-binding motif and is required
for chemotaxis.
supporting_text: Membrane localization required a putative PI(4,5)P2 binding
motif and was required for chemotaxis
- statement: Loss of PTEN broadens and prolongs PIP3 (PH-domain) and actin
polymerization responses, causing circuitous migration.
supporting_text: causing the cells lacking PTEN to follow a circuitous route
toward the attractant
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified primary study establishing PTEN rear-membrane
localization and its role in gradient sensing; abstract supports the cited
claims.
- id: PMID:12062104
title: Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and
PTEN mediates chemotaxis.
findings:
- statement: PTEN shows a pattern of localization reciprocal to PI3K, restricting
PIP3 to the leading edge.
supporting_text: PTEN, a negative regulator of PI3K pathways, exhibits a
reciprocal pattern of localization
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; establishes reciprocal PI3K/PTEN localization
during chemotaxis.
- id: PMID:14764604
title: Novel mechanism of PTEN regulation by its phosphatidylinositol 4,5-bisphosphate
binding motif is critical for chemotaxis.
findings:
- statement: The lipid phosphatase activity of PTEN mediates chemotaxis, and sharp
PIP3 localization requires PTEN at the rear.
supporting_text: the lipid phosphatase activity of PTEN mediates chemotaxis and
that the sharp localization of PI(3,4,5)P3 requires localization of PTEN to
the rear of the cell
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; the PI(4,5)P2-binding motif both localizes PTEN
and regulates its activity. The GO:0034485 5-phosphatase annotation linked to
this PMID conflicts with PTEN's 3-phosphatase mechanism and could not be
verified from the abstract.
- id: PMID:15473840
title: Chemoattractant signaling in dictyostelium discoideum.
findings: []
- id: PMID:16900100
title: Imaging of cell migration.
findings: []
- id: PMID:17462897
title: Chemotaxis in the absence of PIP3 gradients.
findings:
- statement: A PI3K1-5/PTEN sextuple mutant chemotaxes near normally but has a
consistent defect in movement speed.
supporting_text: There is, however, a consistent defect in movement speed in
chemotaxis and especially in random movement
- id: PMID:17517960
title: Chemoattractants and chemorepellents act by inducing opposite polarity in
phospholipase C and PI3-kinase signaling.
findings:
- statement: In chemorepellent gradients the localization of PI3K and PTEN is
reversed relative to chemoattractant gradients.
supporting_text: In 8CPT-cAMP gradients, the localization of PI3K and PTEN is
reversed compared with cAMP gradients
- id: PMID:17606871
title: Locally controlled inhibitory mechanisms are involved in eukaryotic GPCR-mediated
chemosensing.
findings:
- statement: PTEN redistribution tracks receptor/G-protein activation and returns
to baseline upon stimulus withdrawal.
supporting_text: the return of the PIP3 phosphatase PTEN and PHCrac-GFP to their
pre-stimulus distribution
- id: PMID:17623773
title: PTEN plays a role in the suppression of lateral pseudopod formation during
Dictyostelium motility and chemotaxis.
findings:
- statement: PTEN is constitutively localized in the cortex of polarized cells.
supporting_text: PTEN, which is constitutively localized in the cortex of
polarized cells
- statement: PTEN plays a fundamental role in suppressing lateral pseudopod
formation, but not in directional sensing.
supporting_text: PTEN, therefore, plays a fundamental role in the suppression of
lateral pseudopod formation
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; defines PTEN's core role in suppressing lateral
pseudopods.
- id: PMID:19011688
title: Ordered patterns of cell shape and orientational correlation during spontaneous
cell migration.
findings:
- statement: PTEN is localized at the rear of spontaneously migrating cells and
restricts excess pseudopod formation.
supporting_text: phosphatase and tensin homolog, (PTEN), is simultaneously
localized at the rear
- id: PMID:19515202
title: PTEN is a mechanosensing signal transducer for myosin II localization in
Dictyostelium cells.
findings:
- statement: PTEN co-localizes with myosin II at the posterior of migrating cells
and the furrow of dividing cells.
supporting_text: PTEN and myosin II co-localized at the posterior of migrating
cells and furrow region of dividing cells
- statement: pten- cells become multinucleated with reduced furrow myosin II,
indicating a cytokinesis role.
supporting_text: PTEN knockout (pten(-)) cells became multinucleated, and myosin
II significantly decreased in amount at the furrow
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; links PTEN to posterior/furrow localization,
myosin II recruitment, and cytokinesis.
- id: PMID:20562345
title: Self-organization of the phosphatidylinositol lipids signaling system for
random cell migration.
findings:
- statement: PTEN and PI3K are essential regulators of membrane PtdIns lipid
concentrations and are required for self-organized PIP3 waves.
supporting_text: regulators for PtdIns lipid concentrations along the membrane,
were essential for wave generation
- id: PMID:21169559
title: Disruption of PKB signaling restores polarity to cells lacking tumor suppressor
PTEN.
findings:
- statement: PTEN maintains cell polarity required for cytokinesis and chemotaxis
by limiting PIP3 levels.
supporting_text: tumor suppressor PTEN not only controls cell growth but also
maintains cell polarity required for cytokinesis and chemotaxis
- statement: Polarity defects in pten- cells correlate with elevated PKB substrate
phosphorylation.
supporting_text: The polarity defects in pten- cells correlate with elevated
phosphorylations of PKB substrates
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; demonstrates that PTEN's effects on polarity,
cytokinesis and chemotaxis are mediated through PKB (PkbA) substrate
phosphorylation.
- id: PMID:23132928
title: Delineating the core regulatory elements crucial for directed cell migration
by examining folic-acid-mediated responses.
findings:
- statement: PTEN redistributes to the cytosol upon uniform stimulation and is
distributed on the lateral and trailing edge of the membrane during migration.
supporting_text: redistribution of PTEN to the cytosol
- id: PMID:25247494
title: 'PTEN redundancy: overexpressing lpten, a homolog of Dictyostelium discoideum
ptenA, the ortholog of human PTEN, rescues all behavioral defects of the mutant
ptenA-.'
findings:
- statement: Deletion of ptenA causes defects in motility, chemotaxis, aggregation
and multicellular morphogenesis, all rescued by overexpressing lpten.
supporting_text: Deletion of ptenA results in defects in motility, chemotaxis,
aggregation and multicellular morphogenesis
- id: PMID:26317626
title: Microtubule-Mediated Inositol Lipid Signaling Plays Critical Roles in Regulation
of Blebbing.
findings:
- statement: PTEN-null cells extend fewer blebs, implicating PTEN in bleb
regulation via inositol lipid metabolism.
supporting_text: PTEN-null cells extended fewer blebs
- id: PMID:30462573
title: An endogenous chemorepellent directs cell movement by inhibiting pseudopods
at one side of cells.
findings:
- statement: In cAMP chemoattraction, PTEN localizes myosin II to the rear of the
cell.
supporting_text: PTEN to localize myosin II to the rear of a cell
- id: PMID:32111929
title: Single-molecule imaging of PI(4,5)P(2) and PTEN in vitro reveals a positive
feedback mechanism for PTEN membrane binding.
findings:
- statement: PTEN's product PI(4,5)P2 stabilizes PTEN membrane binding, creating a
positive-feedback loop for posterior accumulation.
supporting_text: the enzymatic product, PI(4,5)P2, stabilizes PTEN's
membrane-binding
- statement: PTEN accumulates posteriorly to restrict PIP3 to the anterior,
enabling efficient migration.
supporting_text: accumulating PTEN posteriorly to restrict PI(3,4,5)P3
distribution to the anterior
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; in vitro and in vivo single-molecule evidence for
PI(4,5)P2-dependent stabilization of PTEN at the rear membrane.
- id: PMID:34154396
title: An Autocrine Negative Feedback Loop Inhibits Dictyostelium discoideum Proliferation
through Pathways Including IP3/Ca(2).
findings:
- statement: PTEN is required for polyphosphate-induced proliferation inhibition
and IP3 upregulation.
supporting_text: Polyphosphate upregulates IP3, and this requires GrlD, GefA,
PTEN, PLC, and PiaA
- id: PMID:35186938
title: Gradients of PI(4,5)P(2) and PI(3,5)P(2) Jointly Participate in Shaping the
Back State of Dictyostelium Cells.
findings:
- statement: PTEN preferentially binds liposomes containing PI(4,5)P2 and PI(3,5)P2
in vitro, consistent with a back (rear) targeting property.
supporting_text: Pten preferentially bound to liposomes containing PI(4,5)P2 and
PI(3,5)P2
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: PubMed-verified; in vitro liposome binding supports PTEN PI(3,5)P2
and PI(4,5)P2 binding, though the paper's main focus is the novel back protein
Teep1.
- id: PMID:38940195
title: PTEN and the PTEN-like phosphatase CnrN have both distinct and overlapping
roles in a Dictyostelium chemorepulsion pathway.
findings:
- statement: Cells require both PTEN and CnrN to induce chemorepulsion away from
the secreted chemorepellent AprA and to locally inhibit Ras activation.
supporting_text: require both PTEN and CnrN to locally inhibit Ras activation
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; PTEN and the PTEN-like phosphatase CnrN have
distinct and overlapping roles in AprA chemorepulsion.
core_functions:
- description: PTEN is a phosphatidylinositol-3,4,5-trisphosphate (PIP3) 3-phosphatase
that dephosphorylates the D3 position of PIP3 to regenerate PtdIns(4,5)P2,
directly antagonizing PI3-kinase. Enriched at the rear/lateral plasma membrane
and cortex, it restricts PIP3 to the leading edge, thereby negatively regulating
PI3K/PKB (PkbA) signaling and establishing front-rear polarity for suppression
of lateral pseudopods and directed chemotaxis toward cAMP.
molecular_function:
id: GO:0016314
label: phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
directly_involved_in:
- id: GO:0051898
label: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal
transduction
- id: GO:0030010
label: establishment of cell polarity
- id: GO:0043327
label: chemotaxis to cAMP
locations:
- id: GO:0005886
label: plasma membrane
- id: GO:0005938
label: cell cortex
- id: GO:0031254
label: cell trailing edge
supported_by:
- reference_id: PMID:14764604
supporting_text: the lipid phosphatase activity of PTEN mediates chemotaxis and
that the sharp localization of PI(3,4,5)P3 requires localization of PTEN to
the rear of the cell
- reference_id: PMID:21169559
supporting_text: The polarity defects in pten- cells correlate with elevated
phosphorylations of PKB substrates
- reference_id: PMID:12062103
supporting_text: causing the cells lacking PTEN to follow a circuitous route
toward the attractant
- description: PTEN binds its enzymatic product PtdIns(4,5)P2 (and PI(3,5)P2) through
an N-terminal basic motif, which stabilizes its association with the rear plasma
membrane in a positive-feedback manner and drives its posterior accumulation.
This membrane-targeting binding activity localizes PTEN to the back of migrating
cells, spatially restricting PIP3 to the anterior.
molecular_function:
id: GO:0005546
label: phosphatidylinositol-4,5-bisphosphate binding
directly_involved_in:
- id: GO:0030010
label: establishment of cell polarity
locations:
- id: GO:0005886
label: plasma membrane
- id: GO:0031254
label: cell trailing edge
supported_by:
- reference_id: PMID:32111929
supporting_text: the enzymatic product, PI(4,5)P2, stabilizes PTEN's
membrane-binding
- reference_id: PMID:32111929
supporting_text: accumulating PTEN posteriorly to restrict PI(3,4,5)P3
distribution to the anterior
- description: During cell division PTEN accumulates at the equatorial cortex and
cleavage furrow, where by locally restricting PIP3 it contributes to cortical
myosin II accumulation and successful cytokinesis; loss of PTEN causes
multinucleation.
molecular_function:
id: GO:0016314
label: phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
directly_involved_in:
- id: GO:0000281
label: mitotic cytokinesis
locations:
- id: GO:0032154
label: cleavage furrow
- id: GO:1990753
label: equatorial cell cortex
supported_by:
- reference_id: PMID:19515202
supporting_text: PTEN knockout (pten(-)) cells became multinucleated, and myosin
II significantly decreased in amount at the furrow
- reference_id: PMID:19515202
supporting_text: PTEN and myosin II co-localized at the posterior of migrating
cells and furrow region of dividing cells