PTEN (Phosphatase and Tensin Homolog) is a critical tumor suppressor encoding a dual-specificity phosphatase with both lipid and protein phosphatase activities. Its primary and essential tumor suppressor function is as a phosphatidylinositol-3,4,5-trisphosphate (PIP3) 3-phosphatase that dephosphorylates PIP3 to PIP2, thereby antagonizing PI3K/AKT/mTOR signaling. PTEN also exhibits protein phosphatase activity against serine, threonine, and tyrosine residues, though the lipid phosphatase activity is the critical determinant of tumor suppression. Nuclear PTEN contributes to genomic stability and cell cycle control. PTEN localizes to the plasma membrane, cytosol, and nucleus, with membrane localization mediated by its C2 domain and PDZ-binding motif interactions with scaffold proteins like MAGI-2. Germline mutations cause PTEN Hamartoma Tumor Syndrome (PHTS/Cowden disease), while somatic mutations occur frequently across many cancer types.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: PTEN nuclear localization is well-established. Nuclear PTEN has distinct roles in genomic stability, DNA damage response, and cell cycle control, regulated by PTMs and ubiquitin-dependent trafficking. Reason: Nuclear localization is a conserved and functionally important feature of PTEN, supported by extensive experimental evidence and phylogenetic conservation. Supporting Evidence: PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner PMID:17218261 Ubiquitination regulates PTEN nuclear import and tumor suppression file:human/PTEN/PTEN-deep-research-falcon.md See deep research file for comprehensive analysis |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane localization is essential for PTEN's core lipid phosphatase function. PTEN is recruited to the membrane via its C2 domain and PDZ-binding motif interactions with scaffold proteins like MAGI-2. Reason: Plasma membrane localization is the primary site of PTEN's lipid phosphatase activity against PIP3, essential for its tumor suppressor function. Supporting Evidence: PMID:10760291 PTEN binds to MAGI-2 through an interaction between the PDZ-binding motif of PTEN and the second PDZ domain of MAGI-2. MAGI-2 enhances the ability of PTEN to suppress Akt activation. |
| GO:0042995 cell projection | IBA GO_REF:0000033 | ACCEPT | Summary: PTEN localizes to cell projections, consistent with its role in regulating cell motility through PI3K signaling modulation at the leading edge of cells. Reason: PTEN localization to cell projections is consistent with its role in regulating directed cell migration through local PIP3 levels, a phylogenetically conserved feature. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: PTEN is a central component of PI3K/AKT signaling, acting as the primary negative regulator by dephosphorylating PIP3 to PIP2. Reason: This is the core pathway in which PTEN functions. By removing PIP3, PTEN prevents AKT recruitment and activation, making this a core annotation. Supporting Evidence: PMID:9811831 ectopic expression of the phosphatase in PTEN-deficient tumor cell lines resulted in the inhibition of protein kinase (PK) B/Akt and regulation of cell survival |
| GO:0051896 regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IBA GO_REF:0000033 | MODIFY | Summary: PTEN negatively regulates PI3K/AKT signaling via its lipid phosphatase activity. This is redundant with GO:0051898 (negative regulation) which is more specific. Reason: While accurate, GO:0051898 (negative regulation of PI3K/AKT signaling) is more specific to PTEN's actual role as an antagonist of this pathway. Proposed replacements: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PTEN is found in the cytosol where it can exist in an inactive closed conformation. Cytosolic PTEN can be recruited to membranes for its lipid phosphatase function. Reason: Cytosolic localization is well-established for PTEN and represents a reservoir pool that can be recruited to membranes upon appropriate signals. |
| GO:0046856 phosphatidylinositol dephosphorylation | IBA GO_REF:0000033 | ACCEPT | Summary: PTEN dephosphorylates phosphatidylinositols at the D3 position, with primary activity against PIP3 and PI(3,4)P2. Reason: This is a core biological process annotation that accurately describes PTEN's primary enzymatic function. Supporting Evidence: PMID:9811831 Characterization of the lipid phosphatase activity of PTEN demonstrates that it shows specificity for phosphatidylinositols phosphorylated at the 3 position. |
| GO:0004725 protein tyrosine phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PTEN exhibits protein tyrosine phosphatase activity as part of its dual-specificity phosphatase function, though the lipid phosphatase activity is the critical determinant of tumor suppression. Reason: PTEN has documented protein tyrosine phosphatase activity. While secondary to its lipid phosphatase function for tumor suppression, this is a legitimate enzymatic activity. Supporting Evidence: PMID:9256433 recombinant P-TEN dephosphorylated protein and peptide substrates phosphorylated on serine, threonine, and tyrosine residues, indicating that P-TEN is a dual-specificity phosphatase |
| GO:0016314 phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: This is PTEN's primary enzymatic activity - dephosphorylating PIP3 at the D3 position to produce PIP2. This activity is essential for its tumor suppressor function. Reason: This is the core molecular function of PTEN. The lipid phosphatase activity against PIP3 is the critical determinant of PTEN's tumor suppressor function. Supporting Evidence: PMID:9811831 a missense mutation in PTEN, PTEN-G129E, which is observed in two Cowden disease kindreds, specifically ablates the ability of PTEN to recognize inositol phospholipids as a substrate, suggesting that loss of the lipid phosphatase activity is responsible for the etiology of the disease |
| GO:0048870 cell motility | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PTEN regulates cell motility through its effects on PIP3 levels, which control cell polarity and directed migration. Loss of PTEN enhances cell motility. Reason: While PTEN's regulation of cell motility is well-established, this is a downstream effect of its lipid phosphatase activity rather than a core function. The core function is PIP3 dephosphorylation. Supporting Evidence: PMID:9616126 Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN |
| GO:0004722 protein serine/threonine phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: PTEN has dual-specificity protein phosphatase activity including activity against serine/threonine residues. Reason: This is supported by experimental evidence showing PTEN dephosphorylates serine/threonine substrates. Supporting Evidence: PMID:9256433 recombinant P-TEN dephosphorylated protein and peptide substrates phosphorylated on serine, threonine, and tyrosine residues |
| GO:0004725 protein tyrosine phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of IBA annotation for the same term. PTEN has documented protein tyrosine phosphatase activity. Reason: Consistent with experimental evidence for PTEN's dual-specificity phosphatase activity. |
| GO:0004721 phosphoprotein phosphatase activity | IEA GO_REF:0000043 | ACCEPT | Summary: General phosphoprotein phosphatase activity term. PTEN does have protein phosphatase activity but more specific terms (GO:0004722, GO:0004725) are preferred. Reason: Accurate but less specific than existing annotations. Still valid as a parent term. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: PTEN-Long (PTEN-L/alpha) isoform can be secreted and taken up by other cells. This applies specifically to the N-terminally extended isoform. Reason: The PTEN-L isoform has been shown to be secreted and function in neighboring cells (PMID:23744781). Supporting Evidence: PMID:23744781 A secreted PTEN phosphatase that enters cells to alter signaling and survival |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Duplicate of IBA annotation. Nuclear localization of PTEN is well-established. Reason: Consistent with IBA annotation and extensive experimental evidence for nuclear PTEN. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: PTEN is found in the cytoplasm. Cytosol (GO:0005829) is a more specific term that is also annotated. Reason: Cytoplasmic localization is accurate, though cytosol is the more specific subcellular location. |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000043 | MODIFY | Summary: Very broad term. PTEN dephosphorylates phosphatidylinositols but this is more accurately described as phosphatidylinositol dephosphorylation (GO:0046856). Reason: Too general. GO:0046856 (phosphatidylinositol dephosphorylation) is much more specific and accurate for PTEN's function. Proposed replacements: phosphatidylinositol dephosphorylation |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: PTEN promotes apoptosis by inhibiting PI3K/AKT survival signaling. This is a downstream effect of PTEN's lipid phosphatase activity rather than a direct function. Reason: Apoptosis regulation is a downstream consequence of PTEN's inhibition of AKT survival signaling, not a direct molecular function. Supporting Evidence: PMID:9811831 ectopic expression of the phosphatase in PTEN-deficient tumor cell lines resulted in the inhibition of protein kinase (PK) B/Akt and regulation of cell survival |
| GO:0007399 nervous system development | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: PTEN plays important roles in nervous system development by regulating neuron size, dendritic arborization, and synapse formation through PI3K/AKT/mTOR signaling. Reason: While PTEN has well-documented roles in nervous system development (PTEN mutations cause macrocephaly and autism spectrum disorders), this is a pleiotropic effect of its core lipid phosphatase function. |
| GO:0008285 negative regulation of cell population proliferation | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: PTEN suppresses cell proliferation through its antagonism of PI3K/AKT/mTOR signaling. This is a key aspect of its tumor suppressor function. Reason: While this is a fundamental consequence of PTEN function and central to its tumor suppressor role, it is a downstream effect of PI3K/AKT pathway inhibition rather than a direct molecular function. Supporting Evidence: PMID:10468583 The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region |
| GO:0008289 lipid binding | IEA GO_REF:0000043 | ACCEPT | Summary: PTEN binds phosphatidylinositol lipids as substrates via its C2 domain and phosphatase domain. Reason: PTEN's C2 domain mediates membrane/lipid binding which is essential for its localization and function. |
| GO:0009966 regulation of signal transduction | IEA GO_REF:0000117 | MODIFY | Summary: Very broad term. PTEN specifically regulates PI3K/AKT signal transduction via its lipid phosphatase activity. Reason: Too general. GO:0051898 (negative regulation of PI3K/AKT signaling) is more specific and accurate. Proposed replacements: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| GO:0010604 positive regulation of macromolecule metabolic process | IEA GO_REF:0000117 | REMOVE | Summary: Very broad and vague term with unclear relationship to PTEN's core functions. PTEN actually inhibits anabolic processes by suppressing mTOR signaling. Reason: This annotation is too vague and potentially misleading. PTEN generally suppresses anabolic metabolism through mTOR inhibition rather than promoting macromolecule metabolism. |
| GO:0010648 negative regulation of cell communication | IEA GO_REF:0000117 | MODIFY | Summary: Very broad term. PTEN specifically inhibits PI3K/AKT signaling. Reason: Too general. GO:0051898 (negative regulation of PI3K/AKT signaling) is the specific pathway PTEN regulates. Proposed replacements: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| GO:0016314 phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of IBA annotation. This is PTEN's primary enzymatic activity. Reason: Consistent with IBA annotation and extensive experimental evidence. This is the core molecular function of PTEN. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | ACCEPT | Summary: Very broad parent term for PTEN's phosphatase activities. Reason: While very general, this is technically accurate as a parent term of phosphatase activity. |
| GO:0016791 phosphatase activity | IEA GO_REF:0000002 | ACCEPT | Summary: General phosphatase activity term. More specific terms for lipid and protein phosphatase activities are preferred. Reason: Accurate as a parent term, though more specific annotations exist. |
| GO:0019899 enzyme binding | IEA GO_REF:0000117 | ACCEPT | Summary: PTEN binds multiple enzymes including kinases and ubiquitin ligases that regulate its activity and stability. Reason: PTEN interacts with various enzymes for regulation of its activity, localization, and stability. |
| GO:0023057 negative regulation of signaling | IEA GO_REF:0000117 | MODIFY | Summary: Broad term. PTEN specifically negatively regulates PI3K/AKT signaling. Reason: Too general. GO:0051898 (negative regulation of PI3K/AKT signaling) is more specific. Proposed replacements: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| GO:0030351 inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity | IEA GO_REF:0000116 | ACCEPT | Summary: PTEN can dephosphorylate soluble inositol phosphates in addition to phosphatidylinositol lipids. Reason: This activity has been demonstrated experimentally (PMID:11418101). Supporting Evidence: PMID:11418101 Expanding coincident signaling by PTEN through its inositol 1,3,4,5,6-pentakisphosphate 3-phosphatase activity |
| GO:0045595 regulation of cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: PTEN affects cell differentiation through PI3K/AKT/mTOR pathway modulation. Reason: This is a downstream pleiotropic effect of PTEN's lipid phosphatase activity, not a core function. |
| GO:0046856 phosphatidylinositol dephosphorylation | IEA GO_REF:0000002 | ACCEPT | Summary: Duplicate of IBA annotation. Core biological process for PTEN. Reason: Consistent with IBA annotation. This is a core process term for PTEN's primary function. |
| GO:0051093 negative regulation of developmental process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Very broad term. PTEN affects development through PI3K/AKT pathway regulation. Reason: Downstream pleiotropic effect of PTEN's lipid phosphatase activity. Too general to be informative. |
| GO:0051129 negative regulation of cellular component organization | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Very broad term with unclear mechanistic connection to PTEN's core functions. Reason: This is too vague and likely an over-annotation. PTEN's effects on cellular organization are indirect consequences of PI3K/AKT signaling modulation. |
| GO:0051241 negative regulation of multicellular organismal process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Very broad term with unclear mechanistic basis. Reason: Too vague to be informative. This is an indirect consequence of PTEN's lipid phosphatase activity. |
| GO:0051717 inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: PTEN can dephosphorylate soluble inositol polyphosphates including I(1,3,4,5)P4. Reason: This activity has been demonstrated experimentally (PMID:9593664). Supporting Evidence: PMID:9593664 The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate |
| GO:0051726 regulation of cell cycle | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: PTEN regulates cell cycle through multiple mechanisms including AKT-mediated effects on p27/p21 and nuclear PTEN effects on APC/CDH1. Reason: While PTEN has well-documented effects on cell cycle, these are downstream of its lipid phosphatase activity and nuclear functions, not a primary molecular function. Supporting Evidence: PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner |
| GO:0051800 phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity | IEA GO_REF:0000002 | ACCEPT | Summary: PTEN can dephosphorylate PI(3,4)P2 in addition to PIP3, though PIP3 is the primary substrate. Reason: This is a documented enzymatic activity of PTEN (PMID:9811831). Supporting Evidence: PMID:9811831 Characterization of the lipid phosphatase activity of PTEN demonstrates that it shows specificity for phosphatidylinositols phosphorylated at the 3 position |
| GO:0005515 protein binding | IPI PMID:15951562 Binding of PTEN to specific PDZ domains contributes to PTEN ... | MODIFY | Summary: PTEN binds PDZ domain-containing proteins (MAGI2, MAGI3, MAST1, MAST2, MAST3) through its C-terminal PDZ-binding motif. Reason: Generic protein binding is uninformative. GO:0030165 (PDZ domain binding) is more specific and accurate for this interaction. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:15951562 Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases |
| GO:0005515 protein binding | IPI PMID:16456542 PTEN tumor suppressor associates with NHERF proteins to atte... | MODIFY | Summary: PTEN associates with NHERF proteins to attenuate PDGF receptor signaling. Reason: Generic protein binding is uninformative. More specific term for NHERF/PDZ scaffold binding is preferred. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:16456542 PTEN tumor suppressor associates with NHERF proteins to attenuate PDGF receptor signaling. |
| GO:0005515 protein binding | IPI PMID:17274640 A limited screen for protein interactions reveals new roles ... | MARK AS OVER ANNOTATED | Summary: PTEN interacts with protein phosphatase 1. Reason: Generic protein binding is uninformative. More specific binding terms should be used when the interacting partner is known. Supporting Evidence: PMID:17274640 A limited screen for protein interactions reveals new roles for protein phosphatase 1 in cell cycle control and apoptosis. |
| GO:0005515 protein binding | IPI PMID:19345329 Rak functions as a tumor suppressor by regulating PTEN prote... | MARK AS OVER ANNOTATED | Summary: PTEN interacts with FRK kinase which phosphorylates and stabilizes PTEN. Reason: Generic protein binding is uninformative. The specific interaction with FRK kinase is relevant for PTEN regulation but would be better annotated with a kinase binding term. Supporting Evidence: PMID:19345329 Rak functions as a tumor suppressor by regulating PTEN protein stability and function. |
| GO:0005515 protein binding | IPI PMID:19369943 Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activit... | MARK AS OVER ANNOTATED | Summary: PTEN interacts with peroxiredoxin 1 (Prdx1) which regulates PTEN oxidation. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:19369943 Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity. |
| GO:0005515 protein binding | IPI PMID:19903340 PTEN inhibits BMI1 function independently of its phosphatase... | MARK AS OVER ANNOTATED | Summary: PTEN inhibits BMI1 function independently of its phosphatase activity. Reason: Generic protein binding is uninformative. This interaction represents a non-canonical PTEN function. Supporting Evidence: PMID:19903340 PTEN inhibits BMI1 function independently of its phosphatase activity. |
| GO:0005515 protein binding | IPI PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive comple... | MODIFY | Summary: Nuclear PTEN interacts with the APC-CDH1 complex. Reason: More specific term should be used. GO:0010997 (anaphase-promoting complex binding) is appropriate. Proposed replacements: anaphase-promoting complex binding Supporting Evidence: PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. |
| GO:0005515 protein binding | IPI PMID:21653829 Protein interactome reveals converging molecular pathways am... | MARK AS OVER ANNOTATED | Summary: High-throughput study of protein interactions in autism spectrum disorders. Reason: Generic protein binding from high-throughput study is uninformative without specific interactor information. Supporting Evidence: PMID:21653829 Protein interactome reveals converging molecular pathways among autism disorders. |
| GO:0005515 protein binding | IPI PMID:21804599 PTEN, NHERF1 and PHLPP form a tumor suppressor network that ... | MARK AS OVER ANNOTATED | Summary: PTEN forms a tumor suppressor network with NHERF1 and PHLPP. Reason: Generic protein binding is uninformative. Specific scaffold/adapter binding terms would be more appropriate. Supporting Evidence: PMID:21804599 PTEN, NHERF1 and PHLPP form a tumor suppressor network that is disabled in glioblastoma. |
| GO:0005515 protein binding | IPI PMID:23514585 PTEN suppresses the oncogenic function of AIB1 through decre... | MARK AS OVER ANNOTATED | Summary: PTEN suppresses oncogenic AIB1 by promoting its degradation via Fbw7. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:23514585 PTEN suppresses the oncogenic function of AIB1 through decreasing its protein stability via mechanism involving Fbw7 alpha. |
| GO:0005515 protein binding | IPI PMID:23940795 Phosphorylation of the actin binding protein Drebrin at S647... | MARK AS OVER ANNOTATED | Summary: PTEN interacts with drebrin and regulates its phosphorylation. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:23940795 Phosphorylation of the actin binding protein Drebrin at S647 is regulated by neuronal activity and PTEN. |
| GO:0005515 protein binding | IPI PMID:24012959 Breast cancer-derived K172N, D301V mutations abolish Na+/H+ ... | MODIFY | Summary: PTEN interacts with NHERF1 which regulates PDGF receptor signaling. Reason: Generic protein binding is uninformative. GO:0030165 (PDZ domain binding) is more specific. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:24012959 Epub 2013 Sep 5. Breast cancer-derived K172N, D301V mutations abolish Na+/H+ exchanger regulatory factor 1 inhibition of platelet-derived growth factor receptor signaling. |
| GO:0005515 protein binding | IPI PMID:24656772 SPOP promotes tumorigenesis by acting as a key regulatory hu... | MARK AS OVER ANNOTATED | Summary: PTEN is a substrate of SPOP ubiquitin ligase. Reason: Generic protein binding is uninformative. This represents PTEN regulation by ubiquitination. Supporting Evidence: PMID:24656772 2014 Mar 20. SPOP promotes tumorigenesis by acting as a key regulatory hub in kidney cancer. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MARK AS OVER ANNOTATED | Summary: High-throughput proximity ligation assay study. Reason: Generic protein binding from high-throughput study is uninformative. Supporting Evidence: PMID:25241761 Oct 9. Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | MARK AS OVER ANNOTATED | Summary: Protein interaction study in neurons related to autism. Reason: Generic protein binding from high-throughput study is uninformative. Supporting Evidence: PMID:36950384 eCollection 2023 Mar 8. |
| GO:0042802 identical protein binding | IPI PMID:24766807 Cancer-associated PTEN mutants act in a dominant-negative ma... | ACCEPT | Summary: Cancer-associated PTEN mutants can act in a dominant-negative manner by binding to wild-type PTEN, suggesting PTEN dimerization. Reason: PTEN homodimerization is documented and may be relevant for its regulation and for dominant-negative effects of cancer mutations. Supporting Evidence: PMID:24766807 Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function |
| GO:0006661 phosphatidylinositol biosynthetic process | TAS Reactome:R-HSA-1660499 | MODIFY | Summary: PTEN is involved in phosphatidylinositol metabolism by dephosphorylating 3-phosphorylated phosphoinositides, but this is catabolism not biosynthesis. Reason: PTEN dephosphorylates phosphoinositides (catabolic), not biosynthesis. GO:0046856 (phosphatidylinositol dephosphorylation) is more accurate. Proposed replacements: phosphatidylinositol dephosphorylation |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | TAS Reactome:R-HSA-199456 | ACCEPT | Summary: PTEN negatively regulates PI3K/AKT signaling by dephosphorylating PIP3. This is a core process annotation. Reason: This is the primary biological process in which PTEN functions. Core annotation. Supporting Evidence: PMID:9811831 PTEN functions to suppress these growth-promoting and survival signals by dephosphorylating the phospholipid products of PI 3-kinase |
| GO:0016314 phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity | TAS Reactome:R-HSA-199456 | ACCEPT | Summary: PTEN's primary enzymatic activity. Duplicate of IBA and IDA annotations. Reason: Core molecular function of PTEN. Essential for tumor suppression. |
| GO:0008013 beta-catenin binding | IPI PMID:20123964 Lipid phosphate phosphatase 3 stabilization of beta-catenin ... | UNDECIDED | Summary: PTEN can interact with beta-catenin, potentially regulating Wnt signaling. Reason: The reference PMID:20123964 is about lipid phosphate phosphatase 3 (LPP3), not PTEN directly. Need to verify if this annotation is correctly assigned. Supporting Evidence: PMID:20123964 Feb 1. Lipid phosphate phosphatase 3 stabilization of beta-catenin induces endothelial cell migration and formation of branching point structures. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:20123964 Lipid phosphate phosphatase 3 stabilization of beta-catenin ... | UNDECIDED | Summary: This annotation appears to be from a study on LPP3, not PTEN directly. Reason: Need to verify reference relevance. PMID:20123964 title is about LPP3, not PTEN. Supporting Evidence: PMID:20123964 Feb 1. Lipid phosphate phosphatase 3 stabilization of beta-catenin induces endothelial cell migration and formation of branching point structures. |
| GO:0051800 phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity | IDA PMID:20123964 Lipid phosphate phosphatase 3 stabilization of beta-catenin ... | ACCEPT | Summary: PI(3,4)P2 3-phosphatase activity is documented for PTEN, but this reference appears to be about LPP3. Reason: This activity is well-documented for PTEN (PMID:9811831), though the reference may need correction. Supporting Evidence: PMID:20123964 Feb 1. Lipid phosphate phosphatase 3 stabilization of beta-catenin induces endothelial cell migration and formation of branching point structures. |
| GO:1902533 positive regulation of intracellular signal transduction | IMP PMID:20123964 Lipid phosphate phosphatase 3 stabilization of beta-catenin ... | UNDECIDED | Summary: This annotation appears misattributed. PTEN generally negatively regulates signaling. Reason: PTEN typically inhibits signaling via PI3K/AKT pathway. This positive regulation annotation may be incorrectly assigned or context-specific. Supporting Evidence: PMID:20123964 Feb 1. Lipid phosphate phosphatase 3 stabilization of beta-catenin induces endothelial cell migration and formation of branching point structures. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: PTEN localizes to the nucleoplasm where it has phosphatase-independent functions in genomic stability and chromatin regulation. Reason: Nuclear PTEN is well-documented with important functions including interaction with APC-CDH1 and regulation of genomic stability. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: PTEN is present in the cytosol where it can function as both lipid and protein phosphatase Reason: Cytosolic localization allows PTEN to regulate multiple signaling pathways beyond membrane-associated functions |
| GO:0005886 plasma membrane | IDA PMID:10760291 Evidence for regulation of the PTEN tumor suppressor by a me... | ACCEPT | Summary: PTEN localizes to the plasma membrane where it dephosphorylates PIP3 to antagonize PI3K signaling Reason: Plasma membrane localization is essential for PTEN's core lipid phosphatase function against PIP3 Supporting Evidence: PMID:10760291 Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2. |
| GO:0030351 inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity | IDA PMID:11418101 Expanding coincident signaling by PTEN through its inositol ... | ACCEPT | Summary: PTEN can dephosphorylate soluble inositol polyphosphates. This is a secondary enzymatic activity. Reason: This activity is documented experimentally in the cited reference. Supporting Evidence: PMID:11418101 Expanding coincident signaling by PTEN through its inositol 1,3,4,5,6-pentakisphosphate 3-phosphatase activity |
| GO:0045668 negative regulation of osteoblast differentiation | IDA PMID:22869525 Insulin-like growth factor (IGF) binding protein 2 functions... | KEEP AS NON CORE | Summary: PTEN regulates osteoblast differentiation through PI3K/AKT pathway modulation. Reason: This is a tissue-specific downstream effect of PTEN's lipid phosphatase activity, not a core function. Supporting Evidence: PMID:22869525 Aug 6. Insulin-like growth factor (IGF) binding protein 2 functions coordinately with receptor protein tyrosine phosphatase Ξ² and the IGF-I receptor to regulate IGF-I-stimulated signaling. |
| GO:0051800 phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity | TAS Reactome:R-HSA-1676149 | ACCEPT | Summary: PI(3,4)P2 3-phosphatase activity is documented for PTEN. Duplicate of IEA annotation. Reason: This is a documented enzymatic activity of PTEN (PMID:9811831). |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISS GO_REF:0000024 | ACCEPT | Summary: Core process annotation for PTEN. Duplicate of TAS/IDA annotations. Reason: This is the primary biological process in which PTEN functions. |
| GO:0007270 neuron-neuron synaptic transmission | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN affects synaptic transmission through PI3K/AKT pathway modulation in neurons. Reason: Downstream tissue-specific effect. PTEN mutations cause neurological phenotypes including autism spectrum disorders. |
| GO:0007611 learning or memory | ISS PMID:16675393 Pten regulates neuronal arborization and social interaction ... | KEEP AS NON CORE | Summary: PTEN deletion in mouse neurons affects learning and memory through PI3K/mTOR pathway dysregulation. Reason: Downstream pleiotropic effect based on mouse studies. Not a core molecular function. Supporting Evidence: PMID:16675393 Pten regulates neuronal arborization and social interaction in mice. |
| GO:0007626 locomotory behavior | ISS PMID:16675393 Pten regulates neuronal arborization and social interaction ... | KEEP AS NON CORE | Summary: Neuronal PTEN deletion affects locomotory behavior in mouse studies. Reason: Downstream behavioral effect. Very distant from PTEN's core lipid phosphatase function. Supporting Evidence: PMID:16675393 Pten regulates neuronal arborization and social interaction in mice. |
| GO:0021542 dentate gyrus development | ISS PMID:17706614 A seizure-prone phenotype is associated with altered free-ru... | KEEP AS NON CORE | Summary: PTEN regulates dentate gyrus development via PI3K/AKT pathway. Reason: Tissue-specific developmental effect. Not a core function. Supporting Evidence: PMID:17706614 2007 Jul 20. A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice. |
| GO:0021955 central nervous system neuron axonogenesis | ISS PMID:16675393 Pten regulates neuronal arborization and social interaction ... | KEEP AS NON CORE | Summary: PTEN regulates axon growth through PI3K/mTOR signaling. Reason: Downstream effect on neuronal development. Not a core function. Supporting Evidence: PMID:16675393 Pten regulates neuronal arborization and social interaction in mice. |
| GO:0030534 adult behavior | ISS PMID:16675393 Pten regulates neuronal arborization and social interaction ... | MARK AS OVER ANNOTATED | Summary: PTEN affects adult behavior through neuronal PI3K/AKT signaling. Reason: Too vague and distant from core molecular function. Over-annotation. Supporting Evidence: PMID:16675393 Pten regulates neuronal arborization and social interaction in mice. |
| GO:0032286 central nervous system myelin maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN affects myelination through PI3K/AKT/mTOR signaling. Reason: Cell type-specific effect. Not a core function. |
| GO:0035176 social behavior | ISS PMID:16675393 Pten regulates neuronal arborization and social interaction ... | MARK AS OVER ANNOTATED | Summary: PTEN deletion in neurons affects social behavior (autism-like phenotypes). Reason: Behavioral phenotype very distant from core molecular function. Supporting Evidence: PMID:16675393 Pten regulates neuronal arborization and social interaction in mice. |
| GO:0042711 maternal behavior | ISS PMID:16675393 Pten regulates neuronal arborization and social interaction ... | MARK AS OVER ANNOTATED | Summary: PTEN affects maternal behavior through neuronal functions. Reason: Behavioral phenotype very distant from core molecular function. Supporting Evidence: PMID:16675393 Pten regulates neuronal arborization and social interaction in mice. |
| GO:0043005 neuron projection | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN localizes to and regulates neuron projections. Reason: Cell type-specific localization. Valid but not a core function. |
| GO:0045475 locomotor rhythm | ISS PMID:17706614 A seizure-prone phenotype is associated with altered free-ru... | MARK AS OVER ANNOTATED | Summary: PTEN affects locomotor rhythms through circadian/neuronal mechanisms. Reason: Very indirect behavioral effect. Supporting Evidence: PMID:17706614 2007 Jul 20. A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice. |
| GO:0045792 negative regulation of cell size | ISS PMID:21411674 Pten knockdown in vivo increases excitatory drive onto denta... | KEEP AS NON CORE | Summary: PTEN suppresses cell growth/size through PI3K/mTOR inhibition. Reason: Well-documented downstream effect but not a core molecular function. Supporting Evidence: PMID:21411674 Pten knockdown in vivo increases excitatory drive onto dentate granule cells. |
| GO:0046621 negative regulation of organ growth | ISS PMID:19208814 Haploinsufficiency for Pten and Serotonin transporter cooper... | KEEP AS NON CORE | Summary: PTEN suppresses organ growth via PI3K/AKT/mTOR pathway inhibition. Reason: Downstream pleiotropic effect. Supporting Evidence: PMID:19208814 Haploinsufficiency for Pten and Serotonin transporter cooperatively influences brain size and social behavior. |
| GO:0060024 rhythmic synaptic transmission | ISS PMID:17706614 A seizure-prone phenotype is associated with altered free-ru... | MARK AS OVER ANNOTATED | Summary: PTEN affects rhythmic synaptic transmission in circadian circuits. Reason: Very specialized neuronal function. Supporting Evidence: PMID:17706614 2007 Jul 20. A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice. |
| GO:0060074 synapse maturation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN regulates synapse maturation through PI3K/mTOR signaling. Reason: Neuronal-specific developmental effect. |
| GO:0060134 prepulse inhibition | ISS PMID:19208814 Haploinsufficiency for Pten and Serotonin transporter cooper... | MARK AS OVER ANNOTATED | Summary: PTEN affects sensorimotor gating (prepulse inhibition). Reason: Very specialized behavioral/neurological phenotype. Supporting Evidence: PMID:19208814 Haploinsufficiency for Pten and Serotonin transporter cooperatively influences brain size and social behavior. |
| GO:0060997 dendritic spine morphogenesis | ISS PMID:18082964 Phosphatase and tensin homolog, deleted on chromosome 10 def... | KEEP AS NON CORE | Summary: PTEN regulates dendritic spine morphology through PI3K/mTOR signaling. Reason: Neuronal-specific structural effect. Supporting Evidence: PMID:18082964 Phosphatase and tensin homolog, deleted on chromosome 10 deficiency in brain causes defects in synaptic structure, transmission and plasticity, and myelination abnormalities. |
| GO:0090394 negative regulation of excitatory postsynaptic potential | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN affects synaptic transmission. Reason: Neuronal-specific effect. |
| GO:0097105 presynaptic membrane assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN affects presynaptic structure. Reason: Neuronal-specific structural effect. |
| GO:0097107 postsynaptic density assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN affects postsynaptic structure via PI3K/mTOR signaling. Reason: Neuronal-specific structural effect. |
| GO:1990757 ubiquitin ligase activator activity | ISS PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive comple... | ACCEPT | Summary: Nuclear PTEN activates APC-CDH1 E3 ubiquitin ligase in a phosphatase-independent manner. Reason: This represents a non-canonical function of nuclear PTEN that is independent of its phosphatase activity but important for tumor suppression. Supporting Evidence: PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner |
| GO:2000463 positive regulation of excitatory postsynaptic potential | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN affects synaptic transmission. Reason: Neuronal-specific effect. Note this conflicts with GO:0090394 (negative regulation) which may indicate context-dependency. |
| GO:2000808 negative regulation of synaptic vesicle clustering | ISS PMID:18082964 Phosphatase and tensin homolog, deleted on chromosome 10 def... | KEEP AS NON CORE | Summary: PTEN affects synaptic vesicle organization. Reason: Neuronal-specific structural effect. Supporting Evidence: PMID:18082964 Phosphatase and tensin homolog, deleted on chromosome 10 deficiency in brain causes defects in synaptic structure, transmission and plasticity, and myelination abnormalities. |
| GO:0007056 spindle assembly involved in female meiosis | IDA PMID:31492966 The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic ... | KEEP AS NON CORE | Summary: PTEN degradation is required for oocyte meiotic resumption. PTEN affects spindle assembly during oocyte meiosis. Reason: Specialized cell type-specific role in meiosis. Not a core molecular function. Supporting Evidence: PMID:31492966 Epub 2019 Sep 6. The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic resumption by targeting PTEN degradation. |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IDA PMID:31492966 The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic ... | ACCEPT | Summary: Core process annotation. PTEN negatively regulates PI3K/AKT signaling in oocytes. Reason: Duplicate of TAS/ISS annotations. Core function. Supporting Evidence: PMID:31492966 Epub 2019 Sep 6. The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic resumption by targeting PTEN degradation. |
| GO:0052866 phosphatidylinositol phosphate phosphatase activity | IDA PMID:9811831 The lipid phosphatase activity of PTEN is critical for its t... | ACCEPT | Summary: General phosphatidylinositol phosphate phosphatase activity. The more specific GO:0016314 (PIP3 3-phosphatase) is preferred. Reason: Accurate parent term for PTEN's lipid phosphatase activities. Supporting Evidence: PMID:9811831 Characterization of the lipid phosphatase activity of PTEN demonstrates that it shows specificity for phosphatidylinositols phosphorylated at the 3 position |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5689950 | ACCEPT | Summary: Duplicate nucleoplasm annotation. PTEN localizes to nucleoplasm. Reason: Nuclear PTEN localization is well-established. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6807118 | ACCEPT | Summary: Duplicate nucleoplasm annotation. Reason: Consistent with other nucleoplasm annotations. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6807126 | ACCEPT | Summary: Duplicate nucleoplasm annotation. Reason: Consistent with other nucleoplasm annotations. |
| GO:2000773 negative regulation of cellular senescence | ISS PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive comple... | KEEP AS NON CORE | Summary: Nuclear PTEN affects cellular senescence through APC-CDH1 complex regulation. Reason: Downstream effect of PTEN's nuclear functions. Supporting Evidence: PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. |
| GO:0033137 negative regulation of peptidyl-serine phosphorylation | IMP PMID:10918569 PTEN expression is reduced in a subset of sporadic thyroid c... | KEEP AS NON CORE | Summary: PTEN inhibits AKT-mediated serine phosphorylation of downstream targets by reducing PIP3 levels. Reason: This is an indirect consequence of PTEN's inhibition of AKT signaling. Supporting Evidence: PMID:10918569 PTEN expression is reduced in a subset of sporadic thyroid carcinomas: evidence that PTEN-growth suppressing activity in thyroid cancer cells mediated by p27kip1. |
| GO:1902807 negative regulation of cell cycle G1/S phase transition | IDA PMID:10918569 PTEN expression is reduced in a subset of sporadic thyroid c... | KEEP AS NON CORE | Summary: PTEN inhibits G1/S transition through AKT-mediated effects on cell cycle regulators like p27. Reason: Downstream effect of PI3K/AKT pathway inhibition. Supporting Evidence: PMID:10918569 PTEN expression is reduced in a subset of sporadic thyroid carcinomas: evidence that PTEN-growth suppressing activity in thyroid cancer cells mediated by p27kip1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2317387 | ACCEPT | Summary: Duplicate cytosol annotation. Reason: Consistent with IBA and IDA cytosol annotations. |
| GO:0010977 negative regulation of neuron projection development | ISS PMID:28008308 The Protective Role of microRNA-200c in Alzheimer's Disease ... | KEEP AS NON CORE | Summary: PTEN negatively regulates neuron projection development through PI3K/mTOR signaling. Reason: Neuronal-specific downstream effect. Supporting Evidence: PMID:28008308 eCollection 2016. The Protective Role of microRNA-200c in Alzheimer's Disease Pathologies Is Induced by Beta Amyloid-Triggered Endoplasmic Reticulum Stress. |
| GO:1904706 negative regulation of vascular associated smooth muscle cell proliferation | IMP PMID:26208095 PPARΞ³ Ligands Attenuate Hypoxia-Induced Proliferation in Hum... | KEEP AS NON CORE | Summary: PTEN suppresses vascular smooth muscle cell proliferation through PI3K/AKT pathway inhibition. Reason: Cell type-specific downstream effect of PTEN's core lipid phosphatase function. Supporting Evidence: PMID:26208095 eCollection 2015. PPARΞ³ Ligands Attenuate Hypoxia-Induced Proliferation in Human Pulmonary Artery Smooth Muscle Cells through Modulation of MicroRNA-21. |
| GO:0005515 protein binding | IPI PMID:15355975 Regulation of PTEN phosphorylation and stability by a tumor ... | MARK AS OVER ANNOTATED | Summary: PTEN interacts with NOP53 which regulates PTEN stability. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:15355975 2004 Sep 7. Regulation of PTEN phosphorylation and stability by a tumor suppressor candidate protein. |
| GO:0005515 protein binding | IPI PMID:25007873 TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt... | MARK AS OVER ANNOTATED | Summary: PTEN interacts with PPP1R16B (TIMAP) in endothelial cells. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:25007873 TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells. |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | NAS PMID:16762633 Involvement of human micro-RNA in growth and response to che... | ACCEPT | Summary: Core process annotation. Duplicate of IDA/TAS/ISS annotations. Reason: Core biological process for PTEN. Supporting Evidence: PMID:16762633 Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:22879939 TGFΞ²-stimulated microRNA-21 utilizes PTEN to orchestrate AKT... | ACCEPT | Summary: Core process annotation. Duplicate. Reason: Core biological process for PTEN. Supporting Evidence: PMID:22879939 TGFΞ²-stimulated microRNA-21 utilizes PTEN to orchestrate AKT/mTORC1 signaling for mesangial cell hypertrophy and matrix expansion. |
| GO:0010719 negative regulation of epithelial to mesenchymal transition | IMP PMID:27919618 Electric field-induced suppression of PTEN drives epithelial... | KEEP AS NON CORE | Summary: PTEN suppresses EMT through PI3K/AKT pathway inhibition. Reason: Downstream process related to PTEN's tumor suppressor function. Supporting Evidence: PMID:27919618 Epub 2016 Nov 18. Electric field-induced suppression of PTEN drives epithelial-to-mesenchymal transition via mTORC1 activation. |
| GO:0051548 negative regulation of keratinocyte migration | IMP PMID:27919618 Electric field-induced suppression of PTEN drives epithelial... | KEEP AS NON CORE | Summary: PTEN inhibits keratinocyte migration through PI3K/AKT signaling. Reason: Cell type-specific migration effect. Supporting Evidence: PMID:27919618 Epub 2016 Nov 18. Electric field-induced suppression of PTEN drives epithelial-to-mesenchymal transition via mTORC1 activation. |
| GO:0071257 cellular response to electrical stimulus | IMP PMID:27919618 Electric field-induced suppression of PTEN drives epithelial... | MARK AS OVER ANNOTATED | Summary: PTEN affects cellular responses to electrical stimulation in wound healing contexts. Reason: Very specialized experimental context. Distant from core function. Supporting Evidence: PMID:27919618 Epub 2016 Nov 18. Electric field-induced suppression of PTEN drives epithelial-to-mesenchymal transition via mTORC1 activation. |
| GO:1903690 negative regulation of wound healing, spreading of epidermal cells | IMP PMID:27919618 Electric field-induced suppression of PTEN drives epithelial... | KEEP AS NON CORE | Summary: PTEN inhibits epidermal cell spreading during wound healing. Reason: Tissue-specific effect related to PTEN's effects on cell motility. Supporting Evidence: PMID:27919618 Epub 2016 Nov 18. Electric field-induced suppression of PTEN drives epithelial-to-mesenchymal transition via mTORC1 activation. |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:26280536 Deubiquitylase OTUD3 regulates PTEN stability and suppresses... | ACCEPT | Summary: Core process annotation. Duplicate. Reason: Core biological process for PTEN. Supporting Evidence: PMID:26280536 Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis. |
| GO:1990381 ubiquitin-specific protease binding | IPI PMID:26280536 Deubiquitylase OTUD3 regulates PTEN stability and suppresses... | ACCEPT | Summary: PTEN binds USP13 which deubiquitinates and stabilizes PTEN. Reason: This is a specific binding activity relevant to PTEN regulation. More informative than generic protein binding. Supporting Evidence: PMID:26280536 Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1676149 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Cytosolic localization is well-established for PTEN. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1855205 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-199456 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2321904 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6807106 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6807126 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6807134 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6807206 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8847968 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8847977 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8850945 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8850961 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Consistent with other cytosol annotations. |
| GO:0030336 negative regulation of cell migration | IMP PMID:21573166 Upregulated microRNA-29a by hepatitis B virus X protein enha... | KEEP AS NON CORE | Summary: PTEN inhibits cell migration through PI3K/AKT pathway inhibition. Reason: Downstream effect of PTEN's lipid phosphatase activity. Well-documented but not a core molecular function. Supporting Evidence: PMID:9616126 Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN PMID:21573166 Upregulated microRNA-29a by hepatitis B virus X protein enhances hepatoma cell migration by targeting PTEN in cell culture model. |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:21573166 Upregulated microRNA-29a by hepatitis B virus X protein enha... | ACCEPT | Summary: Core process annotation. Duplicate. Reason: Core biological process for PTEN. Supporting Evidence: PMID:21573166 Upregulated microRNA-29a by hepatitis B virus X protein enhances hepatoma cell migration by targeting PTEN in cell culture model. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6807105 | ACCEPT | Summary: Duplicate nucleoplasm annotation. Reason: Consistent with other nucleoplasm annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6807105 | ACCEPT | Summary: Duplicate cytosol annotation. Reason: Consistent with other cytosol annotations. |
| GO:0005634 nucleus | IDA PMID:24862762 NHERF1/EBP50 controls morphogenesis of 3D colonic glands by ... | ACCEPT | Summary: PTEN nuclear localization is important for its protein phosphatase functions and genomic stability Reason: Nuclear localization enables PTEN's protein phosphatase activity and non-canonical tumor suppressor functions Supporting Evidence: PMID:24862762 NHERF1/EBP50 controls morphogenesis of 3D colonic glands by stabilizing PTEN and ezrin-radixin-moesin proteins at the apical membrane. |
| GO:0005737 cytoplasm | IDA PMID:24862762 NHERF1/EBP50 controls morphogenesis of 3D colonic glands by ... | ACCEPT | Summary: Duplicate cytoplasm annotation. Reason: Cytoplasmic localization is well-established for PTEN. Supporting Evidence: PMID:24862762 NHERF1/EBP50 controls morphogenesis of 3D colonic glands by stabilizing PTEN and ezrin-radixin-moesin proteins at the apical membrane. |
| GO:0008284 positive regulation of cell population proliferation | ISS GO_REF:0000024 | UNDECIDED | Summary: PTEN generally negatively regulates cell proliferation. Positive regulation may be context-specific. Reason: This contradicts PTEN's well-established role as an inhibitor of cell proliferation. May be context-specific or incorrectly assigned. |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | TAS PMID:18082964 Phosphatase and tensin homolog, deleted on chromosome 10 def... | ACCEPT | Summary: Core process annotation. Duplicate. Reason: Core biological process for PTEN. Supporting Evidence: PMID:18082964 Phosphatase and tensin homolog, deleted on chromosome 10 deficiency in brain causes defects in synaptic structure, transmission and plasticity, and myelination abnormalities. |
| GO:0007416 synapse assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN regulates synapse assembly through PI3K/mTOR signaling. Reason: Neuronal-specific developmental effect. |
| GO:0033555 multicellular organismal response to stress | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Very broad term with unclear mechanistic basis. Reason: Too vague to be informative. |
| GO:0048853 forebrain morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN affects forebrain development through PI3K/mTOR signaling regulation of cell growth. Reason: Tissue-specific developmental effect. |
| GO:0050771 negative regulation of axonogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN inhibits axon growth through PI3K/mTOR pathway. Reason: Neuronal-specific effect. |
| GO:0005515 protein binding | IPI PMID:19473982 X-linked inhibitor of apoptosis protein (XIAP) regulates PTE... | MARK AS OVER ANNOTATED | Summary: PTEN interacts with XIAP which ubiquitinates PTEN. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:19473982 2009 May 27. X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization. |
| GO:0046856 phosphatidylinositol dephosphorylation | IMP PMID:21828076 A comprehensive functional analysis of PTEN mutations: impli... | ACCEPT | Summary: Core process annotation. PTEN dephosphorylates phosphatidylinositols. Reason: Core biological process for PTEN. Supporting Evidence: PMID:21828076 Aug 9. A comprehensive functional analysis of PTEN mutations: implications in tumor- and autism-related syndromes. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:17880912 MAGI-2 Inhibits cell migration and proliferation via PTEN in... | KEEP AS NON CORE | Summary: PTEN suppresses cell proliferation through PI3K/AKT pathway inhibition. Reason: Downstream effect of PTEN's core lipid phosphatase activity. Supporting Evidence: PMID:17880912 Epub 2007 Aug 22. MAGI-2 Inhibits cell migration and proliferation via PTEN in human hepatocarcinoma cells. |
| GO:0030336 negative regulation of cell migration | IMP PMID:17880912 MAGI-2 Inhibits cell migration and proliferation via PTEN in... | KEEP AS NON CORE | Summary: PTEN inhibits cell migration. Duplicate annotation. Reason: Downstream effect of PTEN's lipid phosphatase activity. Supporting Evidence: PMID:17880912 Epub 2007 Aug 22. MAGI-2 Inhibits cell migration and proliferation via PTEN in human hepatocarcinoma cells. |
| GO:0005737 cytoplasm | IDA PMID:10760291 Evidence for regulation of the PTEN tumor suppressor by a me... | ACCEPT | Summary: Duplicate cytoplasm annotation. Reason: Consistent with other cytoplasm annotations. Supporting Evidence: PMID:10760291 Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2. |
| GO:0004721 phosphoprotein phosphatase activity | IDA PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive comple... | ACCEPT | Summary: PTEN has phosphoprotein phosphatase activity in the nucleus. Reason: This protein phosphatase activity has been demonstrated experimentally. Supporting Evidence: PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. |
| GO:0005634 nucleus | IDA PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive comple... | ACCEPT | Summary: Nuclear PTEN localization for APC-CDH1 regulation. Reason: Well-documented nuclear localization with specific function. Supporting Evidence: PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. |
| GO:0005737 cytoplasm | IDA PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive comple... | ACCEPT | Summary: Duplicate cytoplasm annotation. Reason: Consistent with other cytoplasm annotations. Supporting Evidence: PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. |
| GO:0010997 anaphase-promoting complex binding | IPI PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive comple... | ACCEPT | Summary: Nuclear PTEN binds the APC-CDH1 complex to activate its E3 ligase activity. Reason: This represents an important phosphatase-independent function of nuclear PTEN. Supporting Evidence: PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner |
| GO:2000060 positive regulation of ubiquitin-dependent protein catabolic process | IDA PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive comple... | KEEP AS NON CORE | Summary: Nuclear PTEN activates APC-CDH1 to promote ubiquitin-dependent degradation of its substrates. Reason: This is a downstream effect of PTEN's interaction with APC-CDH1, not a core function. Supporting Evidence: PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. |
| GO:2000134 negative regulation of G1/S transition of mitotic cell cycle | IDA PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive comple... | KEEP AS NON CORE | Summary: Nuclear PTEN suppresses G1/S transition through APC-CDH1 activation. Reason: Downstream effect of PTEN's nuclear APC-CDH1 activating function. Supporting Evidence: PMID:21241890 Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. |
| GO:0005515 protein binding | IPI PMID:17242191 NHERF1/EBP50 head-to-tail intramolecular interaction masks a... | MARK AS OVER ANNOTATED | Summary: PTEN interacts with DJ-1 which affects PTEN function. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:17242191 Jan 22. NHERF1/EBP50 head-to-tail intramolecular interaction masks association with PDZ domain ligands. |
| GO:0008285 negative regulation of cell population proliferation | IDA PMID:19057511 PTEN regulation by Akt-EGR1-ARF-PTEN axis. | KEEP AS NON CORE | Summary: PTEN suppresses cell proliferation. Duplicate annotation. Reason: Downstream effect of PTEN's lipid phosphatase activity. Supporting Evidence: PMID:19057511 PTEN regulation by Akt-EGR1-ARF-PTEN axis. |
| GO:0005737 cytoplasm | IDA PMID:10940933 Subcellular localization of intracellular protein tyrosine p... | ACCEPT | Summary: Duplicate cytoplasm annotation. Reason: Consistent with other cytoplasm annotations. Supporting Evidence: PMID:10940933 Subcellular localization of intracellular protein tyrosine phosphatases in T cells. |
| GO:0050821 protein stabilization | IDA PMID:20123964 Lipid phosphate phosphatase 3 stabilization of beta-catenin ... | UNDECIDED | Summary: This annotation appears to be from a study on LPP3, not PTEN. Reason: Need to verify reference relevance. PMID:20123964 is about LPP3. Supporting Evidence: PMID:20123964 Feb 1. Lipid phosphate phosphatase 3 stabilization of beta-catenin induces endothelial cell migration and formation of branching point structures. |
| GO:0019899 enzyme binding | IPI PMID:16845383 Critical role for Daxx in regulating Mdm2. | ACCEPT | Summary: PTEN interacts with NDR kinases. Reason: More informative than generic protein binding. Supporting Evidence: PMID:16845383 Critical role for Daxx in regulating Mdm2. |
| GO:0010975 regulation of neuron projection development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN regulates neuron projection development through PI3K/mTOR signaling. Reason: Neuronal-specific effect. |
| GO:0005634 nucleus | IDA PMID:17218261 Ubiquitination regulates PTEN nuclear import and tumor suppr... | ACCEPT | Summary: Nuclear localization of PTEN regulated by ubiquitination. Reason: Consistent with other nuclear PTEN annotations. Supporting Evidence: PMID:17218261 Ubiquitination regulates PTEN nuclear import and tumor suppression |
| GO:0051800 phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity | IDA PMID:9811831 The lipid phosphatase activity of PTEN is critical for its t... | ACCEPT | Summary: PTEN can dephosphorylate PI(3,4)P2 at the D3 position. Reason: Documented enzymatic activity. Supporting Evidence: PMID:9811831 Characterization of the lipid phosphatase activity of PTEN demonstrates that it shows specificity for phosphatidylinositols phosphorylated at the 3 position |
| GO:0051895 negative regulation of focal adhesion assembly | IMP PMID:9616126 Inhibition of cell migration, spreading, and focal adhesions... | KEEP AS NON CORE | Summary: PTEN inhibits focal adhesion formation through PI3K/AKT pathway modulation. Reason: Downstream effect related to PTEN's effects on cell motility. Supporting Evidence: PMID:9616126 Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:10760291 Evidence for regulation of the PTEN tumor suppressor by a me... | ACCEPT | Summary: Core process annotation. PTEN suppresses AKT activation. Reason: Core biological process for PTEN. Supporting Evidence: PMID:10760291 MAGI-2 enhances the ability of PTEN to suppress Akt activation |
| GO:0004438 phosphatidylinositol-3-phosphate phosphatase activity | IDA PMID:9811831 The lipid phosphatase activity of PTEN is critical for its t... | ACCEPT | Summary: PTEN can dephosphorylate PI(3)P. Secondary substrate. Reason: Documented activity, though PIP3 is the primary substrate. Supporting Evidence: PMID:9811831 The lipid phosphatase activity of PTEN is critical for its tumor supressor function. |
| GO:0004722 protein serine/threonine phosphatase activity | IDA PMID:9256433 P-TEN, the tumor suppressor from human chromosome 10q23, is ... | ACCEPT | Summary: PTEN has dual-specificity protein phosphatase activity including serine/threonine. Reason: Core molecular function documented in the seminal paper. Supporting Evidence: PMID:9256433 recombinant P-TEN dephosphorylated protein and peptide substrates phosphorylated on serine, threonine, and tyrosine residues, indicating that P-TEN is a dual-specificity phosphatase |
| GO:0004725 protein tyrosine phosphatase activity | IDA PMID:9256433 P-TEN, the tumor suppressor from human chromosome 10q23, is ... | ACCEPT | Summary: PTEN has protein tyrosine phosphatase activity. Reason: Core molecular function documented experimentally. Supporting Evidence: PMID:9256433 recombinant P-TEN dephosphorylated protein and peptide substrates phosphorylated on serine, threonine, and tyrosine residues |
| GO:0005737 cytoplasm | IDA PMID:9187108 TEP1, encoded by a candidate tumor suppressor locus, is a no... | ACCEPT | Summary: Early documentation of PTEN cytoplasmic localization. Reason: Consistent with other cytoplasm annotations. Supporting Evidence: PMID:9187108 TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. |
| GO:0006470 protein dephosphorylation | IDA PMID:9256433 P-TEN, the tumor suppressor from human chromosome 10q23, is ... | ACCEPT | Summary: PTEN has protein phosphatase activity. Core process for its dual-specificity phosphatase function. Reason: Documented experimentally in the seminal paper. Supporting Evidence: PMID:9256433 recombinant P-TEN dephosphorylated protein and peptide substrates phosphorylated on serine, threonine, and tyrosine residues |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:10468583 The tumor-suppressor activity of PTEN is regulated by its ca... | KEEP AS NON CORE | Summary: PTEN suppresses cell proliferation. Duplicate annotation. Reason: Downstream effect of PTEN's lipid phosphatase activity. Supporting Evidence: PMID:10468583 The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region. |
| GO:0016314 phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity | IDA PMID:9811831 The lipid phosphatase activity of PTEN is critical for its t... | ACCEPT | Summary: Core molecular function of PTEN. This is the primary enzymatic activity. Reason: Essential for tumor suppression. Core molecular function. Supporting Evidence: PMID:9811831 Here we report that a missense mutation in PTEN, PTEN-G129E, which is observed in two Cowden disease kindreds, specifically ablates the ability of PTEN to recognize inositol phospholipids as a substrate, suggesting that loss of the lipid phosphatase activity is responsible for the etiology of the disease |
| GO:0030165 PDZ domain binding | IPI PMID:10646847 Threonine phosphorylation of the MMAC1/PTEN PDZ binding doma... | ACCEPT | Summary: PTEN binds PDZ domains through its C-terminal motif. Important for localization and stability. Reason: Well-documented interaction important for PTEN regulation. Supporting Evidence: PMID:10646847 Threonine phosphorylation of the MMAC1/PTEN PDZ binding domain both inhibits and stimulates PDZ binding. |
| GO:0030165 PDZ domain binding | IPI PMID:10760291 Evidence for regulation of the PTEN tumor suppressor by a me... | ACCEPT | Summary: PTEN binds MAGI-2 PDZ domain. Important for membrane localization and function. Reason: Core binding activity for PTEN localization and function. Supporting Evidence: PMID:10760291 PTEN binds to MAGI-2 through an interaction between the PDZ-binding motif of PTEN and the second PDZ domain of MAGI-2 |
| GO:0030336 negative regulation of cell migration | IMP PMID:9616126 Inhibition of cell migration, spreading, and focal adhesions... | KEEP AS NON CORE | Summary: PTEN inhibits cell migration through PI3K/AKT pathway inhibition. Reason: Downstream effect of PTEN's lipid phosphatase activity. Supporting Evidence: PMID:9616126 Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN |
| GO:0046856 phosphatidylinositol dephosphorylation | IDA PMID:9811831 The lipid phosphatase activity of PTEN is critical for its t... | ACCEPT | Summary: Core biological process for PTEN. Reason: Primary process in which PTEN participates. Supporting Evidence: PMID:9811831 The lipid phosphatase activity of PTEN is critical for its tumor supressor function. |
| GO:0051717 inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity | IDA PMID:9593664 The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid... | ACCEPT | Summary: PTEN can dephosphorylate soluble inositol polyphosphates. Reason: Documented enzymatic activity. Supporting Evidence: PMID:9593664 The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. |
| GO:0005737 cytoplasm | TAS PMID:9367992 A family of putative tumor suppressors is structurally and f... | ACCEPT | Summary: Duplicate cytoplasm annotation. Reason: Consistent with other cytoplasm annotations. Supporting Evidence: PMID:9367992 A family of putative tumor suppressors is structurally and functionally conserved in humans and yeast. |
| GO:0006470 protein dephosphorylation | TAS PMID:9367992 A family of putative tumor suppressors is structurally and f... | ACCEPT | Summary: PTEN has protein dephosphorylation activity. Reason: Part of PTEN's dual-specificity phosphatase function. Supporting Evidence: PMID:9367992 A family of putative tumor suppressors is structurally and functionally conserved in humans and yeast. |
| GO:0007417 central nervous system development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN affects CNS development through PI3K/mTOR signaling. Reason: Tissue-specific developmental effect. |
| GO:0007507 heart development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN affects heart development through PI3K/AKT signaling. Reason: Tissue-specific developmental effect. |
| GO:0016477 cell migration | ISS GO_REF:0000024 | MODIFY | Summary: PTEN regulates cell migration. More specific negative regulation terms exist. Reason: GO:0030336 (negative regulation of cell migration) is more accurate for PTEN's inhibitory effect. Proposed replacements: negative regulation of cell migration |
| GO:0031647 regulation of protein stability | IMP PMID:10866658 Phosphorylation of the PTEN tail regulates protein stability... | KEEP AS NON CORE | Summary: PTEN affects protein stability, possibly through AKT-mediated effects. Reason: Indirect effect through signaling pathway modulation. Supporting Evidence: PMID:10866658 Phosphorylation of the PTEN tail regulates protein stability and function. |
| GO:0016314 phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity | IDA PMID:9593664 The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid... | ACCEPT | Summary: Core molecular function. Duplicate annotation. Reason: Primary enzymatic activity of PTEN. Supporting Evidence: PMID:9593664 The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. |
| GO:0014069 postsynaptic density | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: PTEN localizes to postsynaptic densities in neurons. Reason: Neuronal-specific localization. |
| GO:0016605 PML body | IEA GO_REF:0000044 | ACCEPT | Summary: PTEN can localize to PML nuclear bodies. Reason: Relevant for PTEN's nuclear functions and regulation by ubiquitination. |
| GO:0042995 cell projection | IEA GO_REF:0000117 | ACCEPT | Summary: Duplicate of IBA annotation. PTEN localizes to cell projections. Reason: Consistent with IBA annotation. |
| GO:0043197 dendritic spine | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: PTEN localizes to dendritic spines in neurons. Reason: Neuronal-specific localization. |
| GO:0097225 sperm midpiece | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: PTEN localizes to sperm midpiece. Reason: Cell type-specific localization. |
| GO:0097228 sperm principal piece | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: PTEN localizes to sperm principal piece. Reason: Cell type-specific localization. |
| GO:0140678 molecular function inhibitor activity | IMP PMID:23744781 A secreted PTEN phosphatase that enters cells to alter signa... | ACCEPT | Summary: PTEN-L isoform can be secreted and inhibit PI3K signaling in recipient cells. Reason: This describes the paracrine tumor suppressor activity of secreted PTEN-L. Supporting Evidence: PMID:23744781 A secreted PTEN phosphatase that enters cells to alter signaling and survival |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8850992 | ACCEPT | Summary: Duplicate cytosol annotation. Reason: Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8850997 | ACCEPT | Summary: Duplicate cytosol annotation. Reason: Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8851011 | ACCEPT | Summary: Duplicate cytosol annotation. Reason: Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8873946 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome pathway. Reason: Consistent with other cytosol annotations. PTEN is a cytosolic protein that translocates to the plasma membrane for its lipid phosphatase function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8944497 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome pathway. Reason: Consistent with other cytosol annotations. PTEN is a cytosolic protein that translocates to the plasma membrane for its lipid phosphatase function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8948775 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome pathway. Reason: Consistent with other cytosol annotations. PTEN is a cytosolic protein that translocates to the plasma membrane for its lipid phosphatase function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8948800 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome pathway. Reason: Consistent with other cytosol annotations. PTEN is a cytosolic protein that translocates to the plasma membrane for its lipid phosphatase function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8948832 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome pathway. Reason: Consistent with other cytosol annotations. PTEN is a cytosolic protein that translocates to the plasma membrane for its lipid phosphatase function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9615571 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome pathway. Reason: Consistent with other cytosol annotations. PTEN is a cytosolic protein that translocates to the plasma membrane for its lipid phosphatase function. |
| GO:0016324 apical plasma membrane | IMP PMID:24862762 NHERF1/EBP50 controls morphogenesis of 3D colonic glands by ... | ACCEPT | Summary: PTEN localizes to the apical plasma membrane in polarized epithelial cells, stabilized by NHERF1/EBP50 interaction. Reason: The publication demonstrates that PTEN localizes apically in polarized epithelial cells through its C-terminal PDZ-binding motif interaction with NHERF1. This apical localization is important for maintaining PIP2/PIP3 distribution and epithelial polarity. Supporting Evidence: PMID:24862762 NHERF1 stabilizes PTEN apically through PDZ-domain interactions [5] , and NHERF1 loss leads to PTEN cytosolic redistribution |
| GO:0042995 cell projection | IDA PMID:25007873 TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt... | UNDECIDED | Summary: PTEN localization to cell projections in endothelial cells based on TIMAP colocalization studies. Reason: The publication PMID:25007873 focuses on TIMAP regulation of PTEN activity and shows colocalization, but the full text is not available to confirm specific cell projection localization data. The abstract does not directly address cell projection localization. Supporting Evidence: PMID:25007873 TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells. |
| GO:0035749 myelin sheath adaxonal region | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN localization to myelin sheath adaxonal region inferred from sequence similarity. Reason: This is a highly specialized cell type-specific localization in myelinating Schwann cells. While PTEN plays important roles in myelination, this represents a cell type-specific localization rather than a core function annotation. |
| GO:0043220 Schmidt-Lanterman incisure | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PTEN localization to Schmidt-Lanterman incisures in myelin sheath inferred from sequence similarity. Reason: This is a highly specialized localization in peripheral nerve myelin sheaths. While PTEN is important for Schwann cell function and myelination, this represents a cell type-specific localization rather than a core function annotation. |
| GO:0042995 cell projection | IDA PMID:10760291 Evidence for regulation of the PTEN tumor suppressor by a me... | UNDECIDED | Summary: This annotation is likely incorrect for PMID:10760291, which focuses on MAGI-2 PDZ domain interactions. Reason: PMID:10760291 describes PTEN binding to MAGI-2 at tight junctions in epithelial cell membranes, not specifically cell projections. The cell projection annotation may be a misinterpretation of the membrane localization data. The reference discusses membrane localization through MAGI-2 scaffold interactions but does not specifically characterize cell projection localization. Supporting Evidence: PMID:10760291 Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2. |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:10940933 Subcellular localization of intracellular protein tyrosine p... | ACCEPT | Summary: PTEN localizes to the cytoplasmic side of the plasma membrane in T cells. Reason: The publication directly examines subcellular localization of intracellular protein tyrosine phosphatases including PTEN in T cells. PTEN was found enriched at the plasma membrane, consistent with its function in dephosphorylating membrane-associated PIP3. This localization is essential for its core lipid phosphatase function. Supporting Evidence: PMID:10940933 Most were found in the cytosol and many were enriched at the plasma membrane. |
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