Presenilin-1 is a multi-pass membrane aspartyl protease subunit of the gamma-secretase complex. After endoproteolytic maturation, presenilin-1 N- and C-terminal fragments assemble with nicastrin, APH1, and PEN2 in secretory and endosomal membranes to cleave type I membrane-protein substrates, including APP and Notch receptors. Through this intramembrane protease activity, PSEN1 contributes to amyloid-beta peptide generation, Notch receptor processing, and broader regulated intramembrane proteolysis. Additional evidence links presenilin holoprotein to endoplasmic-reticulum calcium leak/homeostasis and protein-trafficking interactions, but these are secondary to its core gamma-secretase catalytic role.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007219 Notch signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: PSEN1 is the catalytic presenilin subunit of gamma-secretase, which cleaves Notch receptors. The conserved PAINT annotation to Notch signaling is appropriate because Notch receptor processing is a core evolved function of presenilin/gamma-secretase biology. Reason: Gamma-secretase cleaves Notch receptor substrates, and PSEN1 is the catalytic presenilin component of the complex. This is a core function, not only an Alzheimer disease context. Supporting Evidence: PMID:15274632 This enzyme cleaves many type I membrane proteins, including the amyloid beta-protein (Abeta) precursor (APP) and the Notch receptor. |
| GO:0042500 aspartic endopeptidase activity, intramembrane cleaving | IBA GO_REF:0000033 | ACCEPT | Summary: PSEN1 provides the catalytic aspartate protease activity of the gamma-secretase intramembrane protease complex. This molecular-function annotation is central and should be retained. Reason: Structural and biochemical work places the PSEN1 catalytic aspartates in the membrane-embedded active site of human gamma-secretase. Supporting Evidence: PMID:26280335 Among the two catalytic residues, Asp257 is located in the middle of TM6 slightly to the extracellular side, whereas Asp385 maps to the cytoplasmic side of TM7 |
| GO:0055074 calcium ion homeostasis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Presenilin proteins have experimental support for ER calcium leak channel activity independent of gamma-secretase, but this is a secondary function relative to PSEN1's core gamma-secretase protease role. Reason: The annotation is biologically plausible and supported, but calcium homeostasis is best treated as a non-core presenilin activity for this review until the in-vivo physiological scope is separated from disease and cell-culture contexts. Supporting Evidence: PMID:16959576 presenilins account for approximately 80% of passive Ca(2+) leak from the endoplasmic reticulum. |
| GO:0016485 protein processing | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PSEN1 participates in proteolytic processing of membrane proteins as the catalytic presenilin subunit of gamma-secretase. The term is broad, but the PAINT annotation captures a real core process. Reason: The annotation is correct but less informative than the more specific membrane-protein ectodomain/intramembrane proteolysis and amyloid-beta/Notch processing annotations; retain as non-core broad process context. Supporting Evidence: PMID:15274632 yeast cells suggest that PS, NCT, Aph-1, and Pen-2 are necessary and sufficient to reconstitute gamma-secretase activity. |
| GO:0006509 membrane protein ectodomain proteolysis | IBA GO_REF:0000033 | ACCEPT | Summary: PSEN1/gamma-secretase cleaves type I membrane-protein substrates after ectodomain shedding, including APP and Notch receptor fragments. This is a core process annotation. Reason: The annotation reflects PSEN1's conserved role in gamma-secretase substrate processing of membrane proteins. Supporting Evidence: PMID:15274632 Gamma-secretase is a member of an unusual class of proteases with intramembrane catalytic sites. |
| GO:0034205 amyloid-beta formation | IBA GO_REF:0000033 | ACCEPT | Summary: PSEN1-containing gamma-secretase cleaves APP-derived C-terminal fragments and generates amyloid-beta peptides. This is a core substrate processing outcome of PSEN1 gamma-secretase activity. Reason: Purified gamma-secretase and structural studies support PSEN1 as the catalytic subunit responsible for APP cleavage leading to amyloid-beta production. Supporting Evidence: PMID:26280335 Among these components, presenilin is responsible for the AΞ²-producing proteolytic activity7,8. |
| GO:0070765 gamma-secretase complex | IBA GO_REF:0000033 | ACCEPT | Summary: PSEN1 is a core component of the mature gamma-secretase complex, present as N- and C-terminal fragments with nicastrin, APH1, and PEN2. Reason: This cellular-component annotation directly represents the complex in which PSEN1 performs its core catalytic role. Supporting Evidence: PMID:15274632 Extensive mass spectrometry of the purified proteins strongly suggests that PS-NTF/CTF, mNCT, Aph-1, and Pen-2 are the components of active gamma-secretase. |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0000776 kinetochore | IEA GO_REF:0000117 | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0005769 early endosome | IEA GO_REF:0000120 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000120 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0007220 Notch receptor processing | IEA GO_REF:0000117 | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0016020 membrane | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Generic compartment annotation for PSEN1. Reason: The term is too broad to add useful information beyond the more specific membrane, ER/Golgi/endosomal, or gamma-secretase complex annotations. |
| GO:0016485 protein processing | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Broad protein-processing annotation for PSEN1/gamma-secretase substrate cleavage. Reason: Correct but broad; more specific gamma-secretase, APP, Notch, and intramembrane proteolysis terms carry the core functional information. |
| GO:0030424 axon | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0030426 growth cone | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0031901 early endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0031965 nuclear membrane | IEA GO_REF:0000117 | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0035556 intracellular signal transduction | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0042500 aspartic endopeptidase activity, intramembrane cleaving | IEA GO_REF:0000120 | ACCEPT | Summary: PSEN1 is the catalytic presenilin subunit of gamma-secretase, a membrane-embedded aspartyl protease complex that cleaves type I membrane-protein substrates including APP and Notch. Reason: This annotation reflects the core evolved function of PSEN1 in regulated intramembrane proteolysis. Structural and biochemical evidence identify presenilin as the catalytic component of mature gamma-secretase. |
| GO:0042987 amyloid precursor protein catabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0043005 neuron projection | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0045202 synapse | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0070588 calcium ion transmembrane transport | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Presenilins have evidence for ER calcium leak/channel activity independent of gamma-secretase, but this is secondary to the core gamma-secretase role. Reason: Retain as non-core/secondary presenilin biology; evidence supports ER calcium leak activity, but the in-vivo physiological scope is less settled than gamma-secretase proteolysis. |
| GO:0098794 postsynapse | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0005515 protein binding | IPI PMID:11083918 X11 alpha and x11 beta interact with presenilin-1 via their ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:12901838 Presenilin-1 interacts directly with the beta-site amyloid p... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:15322109 Both the sequence and length of the C terminus of PEN-2 are ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:16007100 Autoinhibition of X11/Mint scaffold proteins revealed by the... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:16641999 TMP21 is a presenilin complex component that modulates gamma... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:18201567 Cellular localization of Nicastrin affects amyloid beta spec... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:21115843 Activation and intrinsic gamma-secretase activity of preseni... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:21163940 Interactome mapping suggests new mechanistic details underly... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:25394380 G206D Mutation of Presenilin-1 Reduces Pen2 Interaction, Inc... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:25959826 Quantitative interaction proteomics of neurodegenerative dis... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:26280335 An atomic structure of human Ξ³-secretase. | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:29611543 Intracellular trafficking of TREM2 is regulated by presenili... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:30559186 Bax inhibitor 1 is a Ξ³-secretase-independent presenilin-bind... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:9223340 Interaction between amyloid precursor protein and presenilin... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0001921 positive regulation of receptor recycling | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0003407 neural retina development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0004175 endopeptidase activity | IEA GO_REF:0000120 | MODIFY | Summary: Broad peptidase annotation for the PSEN1 catalytic role in gamma-secretase. Reason: The general peptidase term is true in essence but should be replaced by the specific intramembrane aspartyl endopeptidase activity used for presenilin/gamma-secretase. Proposed replacements: aspartic endopeptidase activity, intramembrane cleaving |
| GO:0004190 aspartic-type endopeptidase activity | IEA GO_REF:0000107 | MODIFY | Summary: Broad peptidase annotation for the PSEN1 catalytic role in gamma-secretase. Reason: The general peptidase term is true in essence but should be replaced by the specific intramembrane aspartyl endopeptidase activity used for presenilin/gamma-secretase. Proposed replacements: aspartic endopeptidase activity, intramembrane cleaving |
| GO:0005634 nucleus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Generic compartment annotation for PSEN1. Reason: The term is too broad to add useful information beyond the more specific membrane, ER/Golgi/endosomal, or gamma-secretase complex annotations. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Generic compartment annotation for PSEN1. Reason: The term is too broad to add useful information beyond the more specific membrane, ER/Golgi/endosomal, or gamma-secretase complex annotations. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000107 | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000107 | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000107 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005938 cell cortex | IEA GO_REF:0000107 | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0006509 membrane protein ectodomain proteolysis | IEA GO_REF:0000120 | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0008021 synaptic vesicle | IEA GO_REF:0000107 | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0008233 peptidase activity | IEA GO_REF:0000107 | MODIFY | Summary: Broad peptidase annotation for the PSEN1 catalytic role in gamma-secretase. Reason: The general peptidase term is true in essence but should be replaced by the specific intramembrane aspartyl endopeptidase activity used for presenilin/gamma-secretase. Proposed replacements: aspartic endopeptidase activity, intramembrane cleaving |
| GO:0009986 cell surface | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0021549 cerebellum development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0030425 dendrite | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Generic compartment annotation for PSEN1. Reason: The term is too broad to add useful information beyond the more specific membrane, ER/Golgi/endosomal, or gamma-secretase complex annotations. |
| GO:0031594 neuromuscular junction | IEA GO_REF:0000107 | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Generic compartment annotation for PSEN1. Reason: The term is too broad to add useful information beyond the more specific membrane, ER/Golgi/endosomal, or gamma-secretase complex annotations. |
| GO:0035253 ciliary rootlet | IEA GO_REF:0000107 | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0042383 sarcolemma | IEA GO_REF:0000107 | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0042734 presynaptic membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0043198 dendritic shaft | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0043524 negative regulation of neuron apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0043589 skin morphogenesis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0044233 mitochondria-associated endoplasmic reticulum membrane contact site | IEA GO_REF:0000107 | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0045296 cadherin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Specific cadherin binding annotation for PSEN1-associated complexes or interactors. Reason: The interaction is biologically relevant but secondary to the core gamma-secretase catalytic role; retain as non-core interaction context. |
| GO:0060828 regulation of canonical Wnt signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0070765 gamma-secretase complex | IEA GO_REF:0000107 | ACCEPT | Summary: PSEN1 is a core component of the mature gamma-secretase complex with nicastrin, APH1, and PEN2. Reason: Complex membership is central to PSEN1 function because isolated presenilin requires the other gamma-secretase subunits for mature protease activity. |
| GO:0097060 synaptic membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0098693 regulation of synaptic vesicle cycle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0099175 regulation of postsynapse organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0140249 protein catabolic process at postsynapse | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:2000059 negative regulation of ubiquitin-dependent protein catabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0005794 Golgi apparatus | IDA GO_REF:0000052 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0000139 Golgi membrane | EXP PMID:10593990 Cell surface presenilin-1 participates in the gamma-secretas... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0000139 Golgi membrane | EXP PMID:8574969 Alzheimer-associated presenilins 1 and 2: neuronal expressio... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005769 early endosome | EXP PMID:25394380 G206D Mutation of Presenilin-1 Reduces Pen2 Interaction, Inc... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005783 endoplasmic reticulum | EXP PMID:25394380 G206D Mutation of Presenilin-1 Reduces Pen2 Interaction, Inc... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:10593990 Cell surface presenilin-1 participates in the gamma-secretas... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:8574969 Alzheimer-associated presenilins 1 and 2: neuronal expressio... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:9738936 Direct association of presenilin-1 with beta-catenin. | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | EXP PMID:10593990 Cell surface presenilin-1 participates in the gamma-secretas... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | EXP PMID:11953314 A presenilin-1/gamma-secretase cleavage releases the E-cadhe... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | EXP PMID:11987239 Identification of the presenilins in hematopoietic cells wit... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0045202 synapse | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0035556 intracellular signal transduction | IMP PMID:10508860 Presenilin 1 suppresses the function of c-Jun homodimers via... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0060090 molecular adaptor activity | IDA PMID:9689133 Presenilin 1 associates with glycogen synthase kinase-3beta ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0007611 learning or memory | IGI PMID:20445063 Memory impairment in transgenic Alzheimer mice requires cell... | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0030425 dendrite | IDA PMID:24012003 Metabotropic glutamate receptor 5 is a coreceptor for Alzhei... | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0010629 negative regulation of gene expression | IGI PMID:28008308 The Protective Role of microRNA-200c in Alzheimer's Disease ... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0007611 learning or memory | IGI PMID:24012003 Metabotropic glutamate receptor 5 is a coreceptor for Alzhei... | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0007611 learning or memory | IGI PMID:24052308 Human LilrB2 is a Ξ²-amyloid receptor and its murine homolog ... | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0007613 memory | IGI PMID:11880515 The relationship between Abeta and memory in the Tg2576 mous... | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0010628 positive regulation of gene expression | IGI PMID:28008308 The Protective Role of microRNA-200c in Alzheimer's Disease ... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0050808 synapse organization | IGI PMID:24012003 Metabotropic glutamate receptor 5 is a coreceptor for Alzhei... | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0004175 endopeptidase activity | IMP PMID:12297508 Mammalian APH-1 interacts with presenilin and nicastrin and ... | MODIFY | Summary: Broad peptidase annotation for the PSEN1 catalytic role in gamma-secretase. Reason: The general peptidase term is true in essence but should be replaced by the specific intramembrane aspartyl endopeptidase activity used for presenilin/gamma-secretase. Proposed replacements: aspartic endopeptidase activity, intramembrane cleaving |
| GO:0004175 endopeptidase activity | IGI PMID:12763021 APH1, PEN2, and Nicastrin increase Abeta levels and gamma-se... | MODIFY | Summary: Broad peptidase annotation for the PSEN1 catalytic role in gamma-secretase. Reason: The general peptidase term is true in essence but should be replaced by the specific intramembrane aspartyl endopeptidase activity used for presenilin/gamma-secretase. Proposed replacements: aspartic endopeptidase activity, intramembrane cleaving |
| GO:0005515 protein binding | IPI PMID:12522139 PEN-2 and APH-1 coordinately regulate proteolytic processing... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0007220 Notch receptor processing | IDA PMID:27608597 Specific combinations of presenilins and Aph1s affect the su... | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0016485 protein processing | IMP PMID:12297508 Mammalian APH-1 interacts with presenilin and nicastrin and ... | KEEP AS NON CORE | Summary: Broad protein-processing annotation for PSEN1/gamma-secretase substrate cleavage. Reason: Correct but broad; more specific gamma-secretase, APP, Notch, and intramembrane proteolysis terms carry the core functional information. |
| GO:0016485 protein processing | IGI PMID:12763021 APH1, PEN2, and Nicastrin increase Abeta levels and gamma-se... | KEEP AS NON CORE | Summary: Broad protein-processing annotation for PSEN1/gamma-secretase substrate cleavage. Reason: Correct but broad; more specific gamma-secretase, APP, Notch, and intramembrane proteolysis terms carry the core functional information. |
| GO:0016485 protein processing | IDA PMID:27608597 Specific combinations of presenilins and Aph1s affect the su... | KEEP AS NON CORE | Summary: Broad protein-processing annotation for PSEN1/gamma-secretase substrate cleavage. Reason: Correct but broad; more specific gamma-secretase, APP, Notch, and intramembrane proteolysis terms carry the core functional information. |
| GO:0034205 amyloid-beta formation | IMP PMID:12297508 Mammalian APH-1 interacts with presenilin and nicastrin and ... | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0034205 amyloid-beta formation | IGI PMID:12763021 APH1, PEN2, and Nicastrin increase Abeta levels and gamma-se... | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0034205 amyloid-beta formation | IDA PMID:27608597 Specific combinations of presenilins and Aph1s affect the su... | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0042987 amyloid precursor protein catabolic process | IMP PMID:12297508 Mammalian APH-1 interacts with presenilin and nicastrin and ... | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0042987 amyloid precursor protein catabolic process | IGI PMID:12763021 APH1, PEN2, and Nicastrin increase Abeta levels and gamma-se... | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0042987 amyloid precursor protein catabolic process | IDA PMID:27608597 Specific combinations of presenilins and Aph1s affect the su... | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0070765 gamma-secretase complex | IDA PMID:12297508 Mammalian APH-1 interacts with presenilin and nicastrin and ... | ACCEPT | Summary: PSEN1 is a core component of the mature gamma-secretase complex with nicastrin, APH1, and PEN2. Reason: Complex membership is central to PSEN1 function because isolated presenilin requires the other gamma-secretase subunits for mature protease activity. |
| GO:0070765 gamma-secretase complex | IGI PMID:12763021 APH1, PEN2, and Nicastrin increase Abeta levels and gamma-se... | ACCEPT | Summary: PSEN1 is a core component of the mature gamma-secretase complex with nicastrin, APH1, and PEN2. Reason: Complex membership is central to PSEN1 function because isolated presenilin requires the other gamma-secretase subunits for mature protease activity. |
| GO:0006974 DNA damage response | IDA PMID:25542424 The miR-193a-3p regulated PSEN1 gene suppresses the multi-ch... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0005515 protein binding | IPI PMID:26094765 Proton myo-inositol cotransporter is a novel Ξ³-secretase ass... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0051117 ATPase binding | IPI PMID:26094765 Proton myo-inositol cotransporter is a novel Ξ³-secretase ass... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0070851 growth factor receptor binding | IPI PMID:26094765 Proton myo-inositol cotransporter is a novel Ξ³-secretase ass... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0010468 regulation of gene expression | IGI PMID:26200696 Dual pathways mediate Ξ²-amyloid stimulated glutathione relea... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0010628 positive regulation of gene expression | IGI PMID:29061364 Inflammatory microglia are glycolytic and iron retentive and... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0010629 negative regulation of gene expression | IGI PMID:29061364 Inflammatory microglia are glycolytic and iron retentive and... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0032760 positive regulation of tumor necrosis factor production | IGI PMID:29061364 Inflammatory microglia are glycolytic and iron retentive and... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0045821 positive regulation of glycolytic process | IGI PMID:29061364 Inflammatory microglia are glycolytic and iron retentive and... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0032469 endoplasmic reticulum calcium ion homeostasis | IMP PMID:25394380 G206D Mutation of Presenilin-1 Reduces Pen2 Interaction, Inc... | KEEP AS NON CORE | Summary: Presenilins have evidence for ER calcium leak/channel activity independent of gamma-secretase, but this is secondary to the core gamma-secretase role. Reason: Retain as non-core/secondary presenilin biology; evidence supports ER calcium leak activity, but the in-vivo physiological scope is less settled than gamma-secretase proteolysis. |
| GO:0010975 regulation of neuron projection development | IMP PMID:15004326 A novel highly pathogenic Alzheimer presenilin-1 mutation in... | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0030426 growth cone | IDA PMID:15004326 A novel highly pathogenic Alzheimer presenilin-1 mutation in... | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0043005 neuron projection | IDA PMID:15004326 A novel highly pathogenic Alzheimer presenilin-1 mutation in... | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0042500 aspartic endopeptidase activity, intramembrane cleaving | IMP PMID:17428795 Ligand binding and calcium influx induce distinct ectodomain... | ACCEPT | Summary: PSEN1 is the catalytic presenilin subunit of gamma-secretase, a membrane-embedded aspartyl protease complex that cleaves type I membrane-protein substrates including APP and Notch. Reason: This annotation reflects the core evolved function of PSEN1 in regulated intramembrane proteolysis. Structural and biochemical evidence identify presenilin as the catalytic component of mature gamma-secretase. |
| GO:1990535 neuron projection maintenance | IGI PMID:20445063 Memory impairment in transgenic Alzheimer mice requires cell... | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0098609 cell-cell adhesion | IMP PMID:11953314 A presenilin-1/gamma-secretase cleavage releases the E-cadhe... | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1251997 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-193682 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-205112 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2220988 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-3928656 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798739 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9013361 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9017817 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839376 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | TAS Reactome:R-NUL-2197556 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | TAS Reactome:R-NUL-9604300 | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:1905908 positive regulation of amyloid fibril formation | IGI PMID:11880515 The relationship between Abeta and memory in the Tg2576 mous... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. Proposed replacements: amyloid-beta formation |
| GO:0004190 aspartic-type endopeptidase activity | NAS PMID:24217950 Ligand-dependent activation of EphA4 signaling regulates the... | MODIFY | Summary: Broad peptidase annotation for the PSEN1 catalytic role in gamma-secretase. Reason: The general peptidase term is true in essence but should be replaced by the specific intramembrane aspartyl endopeptidase activity used for presenilin/gamma-secretase. Proposed replacements: aspartic endopeptidase activity, intramembrane cleaving |
| GO:0048143 astrocyte activation | IGI PMID:20445063 Memory impairment in transgenic Alzheimer mice requires cell... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0002265 astrocyte activation involved in immune response | IGI PMID:23152628 LRP1 in brain vascular smooth muscle cells mediates local cl... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:1904646 cellular response to amyloid-beta | IGI PMID:23152628 LRP1 in brain vascular smooth muscle cells mediates local cl... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. Proposed replacements: amyloid-beta formation |
| GO:0005515 protein binding | IPI PMID:10508860 Presenilin 1 suppresses the function of c-Jun homodimers via... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005634 nucleus | IMP PMID:10508860 Presenilin 1 suppresses the function of c-Jun homodimers via... | MARK AS OVER ANNOTATED | Summary: Generic compartment annotation for PSEN1. Reason: The term is too broad to add useful information beyond the more specific membrane, ER/Golgi/endosomal, or gamma-secretase complex annotations. |
| GO:0005790 smooth endoplasmic reticulum | IDA PMID:10508860 Presenilin 1 suppresses the function of c-Jun homodimers via... | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0032991 protein-containing complex | IMP PMID:10508860 Presenilin 1 suppresses the function of c-Jun homodimers via... | MARK AS OVER ANNOTATED | Summary: Generic compartment annotation for PSEN1. Reason: The term is too broad to add useful information beyond the more specific membrane, ER/Golgi/endosomal, or gamma-secretase complex annotations. |
| GO:0016020 membrane | IDA PMID:26280335 An atomic structure of human Ξ³-secretase. | MARK AS OVER ANNOTATED | Summary: Generic compartment annotation for PSEN1. Reason: The term is too broad to add useful information beyond the more specific membrane, ER/Golgi/endosomal, or gamma-secretase complex annotations. |
| GO:0034205 amyloid-beta formation | IMP PMID:26280335 An atomic structure of human Ξ³-secretase. | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0042500 aspartic endopeptidase activity, intramembrane cleaving | IDA PMID:26280335 An atomic structure of human Ξ³-secretase. | ACCEPT | Summary: PSEN1 is the catalytic presenilin subunit of gamma-secretase, a membrane-embedded aspartyl protease complex that cleaves type I membrane-protein substrates including APP and Notch. Reason: This annotation reflects the core evolved function of PSEN1 in regulated intramembrane proteolysis. Structural and biochemical evidence identify presenilin as the catalytic component of mature gamma-secretase. |
| GO:0042982 amyloid precursor protein metabolic process | IDA PMID:26280335 An atomic structure of human Ξ³-secretase. | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0060828 regulation of canonical Wnt signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0070765 gamma-secretase complex | IDA PMID:26280335 An atomic structure of human Ξ³-secretase. | ACCEPT | Summary: PSEN1 is a core component of the mature gamma-secretase complex with nicastrin, APH1, and PEN2. Reason: Complex membership is central to PSEN1 function because isolated presenilin requires the other gamma-secretase subunits for mature protease activity. |
| GO:0035577 azurophil granule membrane | TAS Reactome:R-HSA-6798739 | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0005515 protein binding | IPI PMID:21143716 Alzheimer's disease-associated ubiquilin-1 regulates preseni... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005886 plasma membrane | IDA PMID:21143716 Alzheimer's disease-associated ubiquilin-1 regulates preseni... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0016235 aggresome | IDA PMID:21143716 Alzheimer's disease-associated ubiquilin-1 regulates preseni... | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0045121 membrane raft | IDA PMID:20299451 Human CRB2 inhibits gamma-secretase cleavage of amyloid prec... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:23794287 Presenilin-1 regulates the expression of p62 to govern p62-d... | MARK AS OVER ANNOTATED | Summary: Annotation reflects a phenotype or regulatory readout from Alzheimer-model, stress, or perturbation experiments rather than a clearly established normal PSEN1 core function. Reason: Do not use disease-progression or transgenic-model readouts as core evolved PSEN1 biology. Retain cautiously as non-core if plausible; mark over-annotated when the term projects a downstream phenotype onto PSEN1. |
| GO:0016020 membrane | IDA PMID:22375059 Different effects of Sec61Ξ±, Sec62 and Sec63 depletion on tr... | MARK AS OVER ANNOTATED | Summary: Generic compartment annotation for PSEN1. Reason: The term is too broad to add useful information beyond the more specific membrane, ER/Golgi/endosomal, or gamma-secretase complex annotations. |
| GO:0060999 positive regulation of dendritic spine development | IMP PMID:21951279 Role of presenilin 1 in structural plasticity of cortical de... | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0000776 kinetochore | IDA PMID:9298903 Alzheimer presenilins in the nuclear membrane, interphase ki... | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0005262 calcium channel activity | IMP PMID:16959576 Presenilins form ER Ca2+ leak channels, a function disrupted... | KEEP AS NON CORE | Summary: Presenilins have evidence for ER calcium leak/channel activity independent of gamma-secretase, but this is secondary to the core gamma-secretase role. Reason: Retain as non-core/secondary presenilin biology; evidence supports ER calcium leak activity, but the in-vivo physiological scope is less settled than gamma-secretase proteolysis. |
| GO:0005790 smooth endoplasmic reticulum | IDA PMID:9632714 The presenilin 1 protein is a component of a high molecular ... | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0005791 rough endoplasmic reticulum | IDA PMID:9632714 The presenilin 1 protein is a component of a high molecular ... | KEEP AS NON CORE | Summary: Broad or low-specificity subcellular location annotation for PSEN1. Reason: This location is too broad or too indirectly connected to the core gamma-secretase function to treat as a core annotation; retain only as non-core context or over-annotated where generic. |
| GO:0005794 Golgi apparatus | IDA PMID:9632714 The presenilin 1 protein is a component of a high molecular ... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005813 centrosome | IDA PMID:9298903 Alzheimer presenilins in the nuclear membrane, interphase ki... | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0008013 beta-catenin binding | IPI PMID:9632714 The presenilin 1 protein is a component of a high molecular ... | KEEP AS NON CORE | Summary: Specific beta-catenin binding annotation for PSEN1-associated complexes or interactors. Reason: The interaction is biologically relevant but secondary to the core gamma-secretase catalytic role; retain as non-core interaction context. |
| GO:0031965 nuclear membrane | IDA PMID:9298903 Alzheimer presenilins in the nuclear membrane, interphase ki... | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0032469 endoplasmic reticulum calcium ion homeostasis | IGI PMID:16959576 Presenilins form ER Ca2+ leak channels, a function disrupted... | KEEP AS NON CORE | Summary: Presenilins have evidence for ER calcium leak/channel activity independent of gamma-secretase, but this is secondary to the core gamma-secretase role. Reason: Retain as non-core/secondary presenilin biology; evidence supports ER calcium leak activity, but the in-vivo physiological scope is less settled than gamma-secretase proteolysis. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:10805794 Behavioral alterations associated with apoptosis and down-re... | KEEP AS NON CORE | Summary: Non-core PSEN1-associated neuronal, synaptic, adhesion, Wnt, or developmental process annotation. Reason: The annotation is plausible from presenilin/gamma-secretase biology or animal/cellular studies, but it is downstream or context-specific rather than the core molecular function. |
| GO:0070765 gamma-secretase complex | IDA PMID:10801983 Presenilin 1 is linked with gamma-secretase activity in the ... | ACCEPT | Summary: PSEN1 is a core component of the mature gamma-secretase complex with nicastrin, APH1, and PEN2. Reason: Complex membership is central to PSEN1 function because isolated presenilin requires the other gamma-secretase subunits for mature protease activity. |
| GO:0030165 PDZ domain binding | IPI PMID:10551805 Identification of a novel PSD-95/Dlg/ZO-1 (PDZ)-like protein... | KEEP AS NON CORE | Summary: Specific PDZ domain binding annotation for PSEN1-associated complexes or interactors. Reason: The interaction is biologically relevant but secondary to the core gamma-secretase catalytic role; retain as non-core interaction context. |
| GO:0032469 endoplasmic reticulum calcium ion homeostasis | IDA PMID:17431506 Familial Alzheimer disease-linked mutations specifically dis... | KEEP AS NON CORE | Summary: Presenilins have evidence for ER calcium leak/channel activity independent of gamma-secretase, but this is secondary to the core gamma-secretase role. Reason: Retain as non-core/secondary presenilin biology; evidence supports ER calcium leak activity, but the in-vivo physiological scope is less settled than gamma-secretase proteolysis. |
| GO:0005640 nuclear outer membrane | IDA PMID:9246482 Two homologous genes causing early-onset familial Alzheimer'... | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0005783 endoplasmic reticulum | IDA PMID:9246482 Two homologous genes causing early-onset familial Alzheimer'... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005794 Golgi apparatus | IDA PMID:9246482 Two homologous genes causing early-onset familial Alzheimer'... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0004175 endopeptidase activity | IDA PMID:8755489 Endoproteolysis of presenilin 1 and accumulation of processe... | MODIFY | Summary: Broad peptidase annotation for the PSEN1 catalytic role in gamma-secretase. Reason: The general peptidase term is true in essence but should be replaced by the specific intramembrane aspartyl endopeptidase activity used for presenilin/gamma-secretase. Proposed replacements: aspartic endopeptidase activity, intramembrane cleaving |
| GO:0016020 membrane | TAS PMID:7596406 Cloning of a gene bearing missense mutations in early-onset ... | MARK AS OVER ANNOTATED | Summary: Generic compartment annotation for PSEN1. Reason: The term is too broad to add useful information beyond the more specific membrane, ER/Golgi/endosomal, or gamma-secretase complex annotations. |
| GO:0005515 protein binding | IPI PMID:9689133 Presenilin 1 associates with glycogen synthase kinase-3beta ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:11076969 Identification of ubiquilin, a novel presenilin interactor t... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:12297508 Mammalian APH-1 interacts with presenilin and nicastrin and ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation to PSEN1. The interaction may be real, but GO:0005515 is not informative about PSEN1 molecular function. Reason: Mark as over-annotated because specific relationships such as gamma-secretase complex membership, substrate processing, beta-catenin/cadherin interactions, or trafficking effects are more informative than generic protein binding. |
| GO:0005783 endoplasmic reticulum | IDA PMID:15274632 Purification and characterization of the human gamma-secreta... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005794 Golgi apparatus | IDA PMID:15274632 Purification and characterization of the human gamma-secreta... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0005886 plasma membrane | IDA PMID:15274632 Purification and characterization of the human gamma-secreta... | ACCEPT | Summary: Subcellular localization consistent with PSEN1/gamma-secretase trafficking and activity in secretory, endosomal, and plasma-membrane compartments. Reason: Retain because endogenous presenilin/gamma-secretase is a multi-pass membrane complex found in ER, Golgi, endosomal, and cell-surface-related membranes; location is contextual rather than a molecular function. |
| GO:0006509 membrane protein ectodomain proteolysis | IDA PMID:15274632 Purification and characterization of the human gamma-secreta... | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0007220 Notch receptor processing | TAS PMID:15274632 Purification and characterization of the human gamma-secreta... | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0016485 protein processing | IDA PMID:15274632 Purification and characterization of the human gamma-secreta... | KEEP AS NON CORE | Summary: Broad protein-processing annotation for PSEN1/gamma-secretase substrate cleavage. Reason: Correct but broad; more specific gamma-secretase, APP, Notch, and intramembrane proteolysis terms carry the core functional information. |
| GO:0042987 amyloid precursor protein catabolic process | TAS PMID:15274632 Purification and characterization of the human gamma-secreta... | ACCEPT | Summary: PSEN1-containing gamma-secretase processes membrane-protein substrates, including APP-derived C-terminal fragments and Notch receptors. Reason: The process is a direct outcome of PSEN1 gamma-secretase catalytic activity and should be retained as core substrate-processing biology. |
| GO:0005739 mitochondrion | IDA PMID:12377771 The novel presenilin-1-associated protein is a proapoptotic ... | UNDECIDED | Summary: Evidence is not sufficient in the cached materials to decide whether this annotation should be retained for PSEN1. Reason: Use UNDECIDED rather than removing curator assertions because the available cached evidence is incomplete or the annotation is unusual enough to require full-text review. |
| GO:0016020 membrane | TAS PMID:8878479 Increased amyloid-beta42(43) in brains of mice expressing mu... | MARK AS OVER ANNOTATED | Summary: Generic compartment annotation for PSEN1. Reason: The term is too broad to add useful information beyond the more specific membrane, ER/Golgi/endosomal, or gamma-secretase complex annotations. |
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Download this section (compressed HTML)Q: Which PSEN1/gamma-secretase substrates are established normal in-vivo substrates across tissues, rather than inferred from disease models or overexpression systems?
Suggested experts: GO membrane proteolysis curators, gamma-secretase biology experts
Q: Should presenilin ER calcium leak/channel activity be curated as a conserved normal PSEN1 molecular function, or kept as context-dependent non-core biology pending stronger in-vivo evidence?
Suggested experts: calcium signaling experts, neurobiology curators
Q: Which PSEN1 subcellular locations reflect endogenous active gamma-secretase complexes versus isolated holoprotein, overexpression, or interactor-specific experiments?
Suggested experts: cell biology curators, gamma-secretase complex experts
Experiment: Use endogenous tagging and substrate-specific reporters in physiologic human neuronal and non-neuronal cells to separate active gamma-secretase localization from total PSEN1 holoprotein localization.
Hypothesis: Only a subset of PSEN1-positive compartments contain mature gamma-secretase complexes responsible for APP and Notch substrate cleavage.
Type: endogenous tagging/substrate reporter imaging
Experiment: Compare wild-type PSEN1, catalytically inactive PSEN1, and calcium-leak-defective PSEN1 variants in knock-in cells or animal models under non-disease baseline conditions.
Hypothesis: ER calcium homeostasis is a separable normal presenilin activity rather than only a phenotype of familial Alzheimer variants or cellular stress.
Type: knock-in physiology/calcium imaging
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The complete normal in-vivo substrate scope of PSEN1-containing gamma-secretase across tissues is unresolved. APP and Notch are established substrates, but which additional candidate substrates or interactors should be treated as evolved PSEN1 functions rather than overexpression, disease-model, or context-specific cleavage events remains unsettled.
OPEN BIOLOGYCURATION RESIDUAL_SUBGAP
What is known: PSEN1 is the catalytic presenilin subunit of the mature gamma-secretase complex, and the complex cleaves type I membrane-protein substrates including APP and Notch receptors.
Significance: PSEN1 has many GO annotations derived from substrate or interactor studies. Distinguishing conserved, normal substrate biology from context-specific cleavage or disease-model readouts is essential for deciding which biological-process annotations are core, non-core, or over-annotated.
What would resolve it: Endogenous substrate profiling across relevant human cell types, paired with catalytically inactive PSEN1 controls and substrate-specific rescue/readout assays, would define which substrate cleavages represent normal PSEN1 biology.
Provenance (the field's own admissions):
Gap: The physiological scope of PSEN1-mediated ER calcium leak/homeostasis is unresolved. It is not yet clear which calcium-homeostasis annotations reflect a conserved normal presenilin function in vivo versus phenotypes of familial-Alzheimer variants, knockout systems, or cellular stress models.
OPEN BIOLOGYCURATION RESIDUAL_SUBGAP
What is known: Presenilins can form ER Ca2+ leak channels in experimental systems, and this activity is separable from gamma-secretase proteolysis.
Significance: Calcium homeostasis is a real presenilin-associated activity but is secondary to the core gamma-secretase function in this review. Clarifying its normal in-vivo scope would determine whether calcium terms should remain non-core context or be promoted as a conserved PSEN1 function.
What would resolve it: Knock-in comparison of wild-type, protease-dead, and calcium-leak-defective PSEN1 variants under baseline non-disease conditions, with ER calcium measurements in physiologic cell types, would separate normal calcium function from disease/stress phenotypes.
Provenance (the field's own admissions):
Gap: The compartment-specific map of endogenous active PSEN1/gamma-secretase is incomplete. Many location annotations refer to membranes compatible with PSEN1 trafficking, but unusual or low-specificity locations still need to be separated from overexpressed holoprotein, isolated interactor experiments, or inactive/non-mature presenilin pools.
OPEN CURATION CC_DARK
What is known: The review supports mature gamma-secretase activity in secretory, endosomal, and plasma-membrane compartments, and records several unusual location annotations as UNDECIDED rather than removing them without full-text review.
Significance: PSEN1 has many compartment annotations. A curated distinction between endogenous active gamma-secretase complexes and broader PSEN1 holoprotein or interactor localization would reduce over-annotation while preserving real trafficking biology.
What would resolve it: Endogenous tagging combined with substrate-cleavage reporters and mature-complex markers should map active gamma-secretase compartments separately from total PSEN1 localization.
Provenance (the field's own admissions):
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