Aph1a encodes gamma-secretase subunit APH-1A, a seven-pass integral membrane protein and essential non-catalytic subunit of the gamma-secretase intramembrane protease, together with a presenilin catalytic subunit, nicastrin and PEN-2. APH-1A binds nicastrin early in assembly in the endoplasmic reticulum and acts as a scaffold for the complex; it also associates with full-length and C-terminal fragments of substrates such as APP and Jagged, using conserved intramembrane histidines (His-171, His-197). The complex cleaves type I membrane proteins within the membrane after ectodomain shedding, releasing intracellular domains (AICD, NICD) and generating amyloid-beta from APP. In rat brain APH-1A is found with active gamma-secretase in endosome-enriched fractions, synaptic membranes and synaptic vesicles. Mouse Aph1a loss is embryonic lethal with Notch-like defects.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001656 metanephros development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Mouse Aph1a-derived acts-upstream annotation to metanephros development; reflects requirement of Aph1a-containing gamma-secretase for Notch-dependent development rather than a step Aph1a performs. Reason: The acts_upstream_of_or_within qualifier correctly frames this as an indirect, genetic requirement: Aph1a null mice have pleiotropic Notch-like developmental defects, and nephrogenesis depends on gamma-secretase-mediated Notch signalling. Aph1a contributes through gamma-secretase, so the claim is true but peripheral; it is not a core process of the protein. Supporting Evidence: PMID:15665098 Aph1A-/- embryos show a lethal phenotype characterized by angiogenesis defects in the yolk sac, neuronal tube malformations, and mild somitogenesis defects. file:rat/Aph1a/Aph1a-uniprot.txt Potential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors. |
| GO:0005769 early endosome | IDA PMID:20126630 Synaptic and endosomal localization of active gamma-secretas... | ACCEPT | Summary: Aph-1aL co-fractionated with the other gamma-secretase components in rat brain iodixanol fractions whose activity correlated best with the early endosome marker syntaxin 13. Reason: Direct rat-brain fractionation evidence (Western blot of Aph-1aL in the active, syntaxin 13-enriched fractions) supports an endosomal location. gamma-secretase activity correlated best with this compartment, so it is a core location of the cleavage activity, alongside the plasma membrane. Supporting Evidence: PMID:20126630 The Ξ³-sectretase components nicastrin, PS1-CTF, PS2-CTF, Aph-1aL and Pen-2 were enriched in fraction 5β7 of this gradient PMID:20126630 the marker that showed the best correlation with Ξ³-secretase activity was the early endosomal marker syntaxin 13 |
| GO:0005783 endoplasmic reticulum | ISO GO_REF:0000121 | ACCEPT | Summary: ER location transferred from human APH1A, where APH1A is detected in ER and nascent gamma-secretase assembly begins in the ER. Reason: Root organelle check: the human source rests on direct localization of APH1A in ER membranes, and Aph-1 binding nicastrin is thought to initiate complex assembly in the ER. The organelle claim holds; the sub-compartment (ER membrane) is carried by a separate row. The seven TM helices fit an integral ER membrane protein. Supporting Evidence: PMID:20145246 have suggested that it may initiate complex assembly in the endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Aph1a is a seven-pass integral membrane protein; ER membrane is the site of gamma-secretase assembly. Reason: Seven predicted TM helices plus the early assembly role of Aph-1 in the ER support ER membrane location for the rat ortholog. Supporting Evidence: PMID:20145246 have suggested that it may initiate complex assembly in the endoplasmic reticulum file:rat/Aph1a/Aph1a-uniprot.txt Multi-pass membrane protein |
| GO:0005794 Golgi apparatus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Golgi location transferred from human APH1A; the mature gamma-secretase complex traffics through the Golgi/late secretory pathway. Reason: Root organelle check: the human source is a direct localization; rat brain data show partial co-localization of active gamma-secretase with cis-Golgi GM130. Organelle claim holds but is a trafficking station rather than the core site of action. Supporting Evidence: PMID:20126630 In addition, we detected some co-localization between active Ξ³-secretase and the cis-Golgi marker GM130 (Figure 5C). |
| GO:0005886 plasma membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Plasma membrane location transferred from human APH1A; a fraction of active gamma-secretase is at the cell surface. Reason: In rat brain, gamma-secretase activity also correlated with the plasma membrane marker N-cadherin, and a cell-surface pool of the active complex is well documented, so the plasma membrane is a core location of the cleavage activity, alongside the early endosome. Supporting Evidence: PMID:20126630 In addition, the plasma membrane marker N-cadherin correlated well with Ξ³-secretase activity. |
| GO:0006508 proteolysis | IEA GO_REF:0000117 | MODIFY | Summary: ARBA-derived proteolysis; true for the gamma-secretase complex but too general. Reason: Aph1a is part of an intramembrane-cleaving protease complex; the specific process is release of intracellular domains by intramembrane proteolysis, which the gene already carries (GO:0031293 is_a GO:0006508, checked with OAK). Proposed replacements: membrane protein intracellular domain proteolysis Supporting Evidence: PMID:20145246 It mediates the intramembrane proteolysis of many type 1 proteins file:rat/Aph1a/Aph1a-uniprot.txt Potential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors. |
| GO:0006509 membrane protein ectodomain proteolysis | ISO GO_REF:0000121 | MODIFY | Summary: Ectodomain proteolysis transferred from a human IDA; gamma-secretase cleaves within the membrane after ectodomain shedding by other proteases and releases intracellular domains, not ectodomains. Reason: GO:0006509 is defined as cleavage releasing the ectodomain, which is performed by alpha/beta-secretases (sheddases), not by gamma-secretase. The intended process is intramembrane cleavage releasing the intracellular domain (AICD, NICD), GO:0031293, which the gene already carries. The human source row (HGNC-UCL, PMID:15274632) appears to use the wrong term. Propagation Review Root cause: SOURCE BAD Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q96BI3 SOURCE BAD Human APH1A IDA row (PMID:15274632) to ectodomain proteolysis; gamma-secretase performs the intramembrane cleavage after shedding, so the donor term is wrong; the human review MODIFIES it to GO:0031293. Proposed replacements: membrane protein intracellular domain proteolysis Supporting Evidence: PMID:20145246 It mediates the intramembrane proteolysis of many type 1 proteins PMID:20126630 In both cases, the APP intracellular domain (AICD) is released into the cytosol upon Ξ³-secretase cleavage. |
| GO:0007219 Notch signaling pathway | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule-based Notch signaling pathway; gamma-secretase performs the S3 cleavage that releases the Notch intracellular domain, a required step of canonical Notch signalling. Reason: Aph1a-containing gamma-secretase executes the proteolytic step that converts ligand-activated Notch into the signalling NICD, so Aph1a takes part in the pathway. In the current GO build GO:0007220 Notch receptor processing is not a descendant of GO:0007219 (checked with OAK), so this row is not redundant. Supporting Evidence: file:rat/Aph1a/Aph1a-uniprot.txt Potential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors. PMID:20145246 Moreover, the Notch ligands, Delta and Jagged, are substrates of Ξ³-secretase |
| GO:0007220 Notch receptor processing | ISO GO_REF:0000121 | ACCEPT | Summary: Mouse-derived Notch receptor processing (acts upstream of or within). Reason: Gamma-secretase-mediated Notch S3 cleavage is a core activity of Aph1a-containing complexes, and Aph1a null mice show Notch-like developmental defects. Supporting Evidence: file:rat/Aph1a/Aph1a-uniprot.txt Potential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors. PMID:15665098 Aph1A-/- embryos show a lethal phenotype characterized by angiogenesis defects in the yolk sac, neuronal tube malformations, and mild somitogenesis defects. |
| GO:0007220 Notch receptor processing | ISO GO_REF:0000121 | ACCEPT | Summary: Human-derived Notch receptor processing. Reason: Core gamma-secretase substrate processing; consistent with UniRule function statement for the family. Supporting Evidence: file:rat/Aph1a/Aph1a-uniprot.txt Potential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors. |
| GO:0008021 synaptic vesicle | IDA PMID:20126630 Synaptic and endosomal localization of active gamma-secretas... | KEEP AS NON CORE | Summary: Aph-1aL detected in crude and CPG-purified rat brain synaptic vesicle fractions. Reason: Direct rat-brain biochemical evidence: gamma-secretase components including Aph-1aL are present in highly purified synaptic vesicles. A real neuronal location, but peripheral to the core function. Supporting Evidence: PMID:20126630 We conclude that both the synaptic membrane and the synaptic vesicle fractions have high Ξ³-secretase activity and that the Ξ³-secretase components are found also in highly pure synaptic vesicles. |
| GO:0008150 biological_process | ND GO_REF:0000015 | REMOVE | Summary: ND root-term annotation; biological processes of Aph1a are known. Reason: An ND (no biological data) annotation to the BP root is superseded: Aph1a is a gamma-secretase subunit with experimentally supported roles in intramembrane proteolysis of APP and Notch, represented by other rows in this review. Supporting Evidence: file:rat/Aph1a/Aph1a-uniprot.txt Potential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors. PMID:20145246 the beta-amyloid precursor protein holoprotein and its C-terminal fragments, the immediate substrates of gamma-secretase, can associate with Aph-1 |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: Generic membrane from InterPro/UniRule/SubCell mapping; correct but uninformative. Reason: Aph1a is a seven-pass integral membrane protein; the specific supported location is ER membrane (already carried by the gene), with additional plasma membrane and synaptic membrane pools. Proposed replacements: endoplasmic reticulum membrane plasma membrane Supporting Evidence: file:rat/Aph1a/Aph1a-uniprot.txt Multi-pass membrane protein PMID:20145246 have suggested that it may initiate complex assembly in the endoplasmic reticulum |
| GO:0016020 membrane | ISO GO_REF:0000121 | MODIFY | Summary: Generic membrane transferred from human; correct but uninformative. Reason: As for the IEA membrane row: replace with the specific membranes supported for the rat protein (ER membrane, plasma membrane), both already carried by the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q96BI3 SUPPORTS TRANSFER Human APH1A membrane localization is sound; the transferred term is simply less specific than the supported membranes. Proposed replacements: endoplasmic reticulum membrane plasma membrane Supporting Evidence: file:rat/Aph1a/Aph1a-uniprot.txt Multi-pass membrane protein PMID:20145246 have suggested that it may initiate complex assembly in the endoplasmic reticulum |
| GO:0016485 protein processing | IEA GO_REF:0000120 | ACCEPT | Summary: Protein processing by the Aph1a-containing gamma-secretase complex (intramembrane cleavage of APP, Notch and other type I proteins). Reason: Gamma-secretase processes membrane-protein substrates (APP C-terminal fragments, Notch) into signalling or secreted fragments; Aph1a is an essential subunit. GO:0007220 and GO:0031293 are not descendants of GO:0016485 in the current GO build (checked with OAK), so this term is not redundant with them. Supporting Evidence: PMID:20145246 It mediates the intramembrane proteolysis of many type 1 proteins PMID:20145246 the beta-amyloid precursor protein holoprotein and its C-terminal fragments, the immediate substrates of gamma-secretase, can associate with Aph-1 |
| GO:0016485 protein processing | ISO GO_REF:0000121 | ACCEPT | Summary: Protein processing by the Aph1a-containing gamma-secretase complex (intramembrane cleavage of APP, Notch and other type I proteins). Reason: Gamma-secretase processes membrane-protein substrates (APP C-terminal fragments, Notch) into signalling or secreted fragments; Aph1a is an essential subunit. GO:0007220 and GO:0031293 are not descendants of GO:0016485 in the current GO build (checked with OAK), so this term is not redundant with them. Supporting Evidence: PMID:20145246 It mediates the intramembrane proteolysis of many type 1 proteins PMID:20145246 the beta-amyloid precursor protein holoprotein and its C-terminal fragments, the immediate substrates of gamma-secretase, can associate with Aph-1 |
| GO:0016485 protein processing | ISO GO_REF:0000121 | ACCEPT | Summary: Protein processing by the Aph1a-containing gamma-secretase complex (intramembrane cleavage of APP, Notch and other type I proteins). Reason: Gamma-secretase processes membrane-protein substrates (APP C-terminal fragments, Notch) into signalling or secreted fragments; Aph1a is an essential subunit. GO:0007220 and GO:0031293 are not descendants of GO:0016485 in the current GO build (checked with OAK), so this term is not redundant with them. Supporting Evidence: PMID:20145246 It mediates the intramembrane proteolysis of many type 1 proteins PMID:20145246 the beta-amyloid precursor protein holoprotein and its C-terminal fragments, the immediate substrates of gamma-secretase, can associate with Aph-1 |
| GO:0019899 enzyme binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Enzyme binding transferred from mouse; Aph1a binds the presenilin/nicastrin components of the protease complex. Reason: Aph1a binds subunits of the gamma-secretase enzyme as part of complex assembly; true but uninformative, and the informative function is captured by the adaptor activity and complex membership. Supporting Evidence: PMID:20145246 Gamma-secretase is a ubiquitous, multiprotein enzyme composed of presenilin, nicastrin, Aph-1, and Pen-2. PMID:20145246 have suggested that it may initiate complex assembly in the endoplasmic reticulum |
| GO:0030674 protein-macromolecule adaptor activity | ISO GO_REF:0000121 | ACCEPT | Summary: Aph1a acts as an assembly scaffold/adaptor in gamma-secretase, binding nicastrin early and bringing substrates to the complex. Reason: Aph-1 is the scaffold that initiates gamma-secretase assembly and also associates with full-length and CTF substrates (APP, Jagged; endogenous rat Aph-1 bound Jagged-1 in embryo microsomes). This is the best available MF for the non-catalytic subunit. Supporting Evidence: PMID:20145246 have suggested that it may initiate complex assembly in the endoplasmic reticulum PMID:20145246 the beta-amyloid precursor protein holoprotein and its C-terminal fragments, the immediate substrates of gamma-secretase, can associate with Aph-1 PMID:20145246 we were able to observe an interaction between endogenous Jagged-1 and endogenous Aph-1 |
| GO:0031293 membrane protein intracellular domain proteolysis | ISO GO_REF:0000121 | ACCEPT | Summary: Release of intracellular domains (AICD, NICD) by gamma-secretase intramembrane cleavage. Reason: Core process of the Aph1a-containing gamma-secretase. Supporting Evidence: PMID:20145246 It mediates the intramembrane proteolysis of many type 1 proteins PMID:20126630 In both cases, the APP intracellular domain (AICD) is released into the cytosol upon Ξ³-secretase cleavage. |
| GO:0034205 amyloid-beta formation | ISO GO_REF:0000121 | ACCEPT | Summary: Amyloid-beta formation by gamma-secretase cleavage of APP C-terminal fragments. Reason: Aph1a is a subunit of the enzyme that performs the gamma cleavage generating Abeta (the enzyme does the work; APP is the substrate). Rat brain fractions containing Aph-1aL produce Abeta40. Supporting Evidence: PMID:20126630 gamma-Secretase is crucial for the generation of the neurotoxic amyloid beta-peptide (Abeta) PMID:20145246 the beta-amyloid precursor protein holoprotein and its C-terminal fragments, the immediate substrates of gamma-secretase, can associate with Aph-1 |
| GO:0042734 presynaptic membrane | IDA PMID:20126630 Synaptic and endosomal localization of active gamma-secretas... | KEEP AS NON CORE | Summary: SynGO IDA: active gamma-secretase in synaptic membrane fractions and co-localizing with presynaptic synapsin in neurons. Reason: Rat-brain synaptic membrane fractions contain Aph-1aL and produce AICD/Abeta, and active-site labelling co-localizes mainly with presynaptic synapsin. Presynaptic membrane is a plausible, peripheral neuronal location; the synaptic membrane fraction does not separate pre- from postsynaptic membranes, so this is not core. Supporting Evidence: PMID:20126630 The Ξ³-secretase components were present in both the synaptic membrane and synaptic vesicle fractions, but the degree of enrichment varied between experiments. PMID:20126630 The neurons showed extensive co-localization of Ξ³-secretase and the pre-synaptic marker synapsin (Figure 6D), whereas the co-localization with the post-synaptic marker PSD-95 was rare (Figure 6E). |
| GO:0042734 presynaptic membrane | IEP PMID:20126630 Synaptic and endosomal localization of active gamma-secretas... | KEEP AS NON CORE | Summary: SynGO IEP duplicate of the presynaptic membrane location from the same paper. Reason: Same claim and same evidence as the IDA row, so the same action. The evidence is subcellular fractionation and imaging, which is direct-assay (IDA) evidence; IEP (expression pattern) appears to be the wrong code. Supporting Evidence: PMID:20126630 The Ξ³-secretase components were present in both the synaptic membrane and synaptic vesicle fractions, but the degree of enrichment varied between experiments. PMID:20126630 The neurons showed extensive co-localization of Ξ³-secretase and the pre-synaptic marker synapsin (Figure 6D), whereas the co-localization with the post-synaptic marker PSD-95 was rare (Figure 6E). |
| GO:0042982 amyloid precursor protein metabolic process | ISO GO_REF:0000121 | MODIFY | Summary: APP metabolic process; true but less specific than the APP catabolic process the gene carries. Reason: Gamma-secretase cleaves APP C-terminal fragments, i.e. APP catabolism; GO:0042987 is_a GO:0042982 (checked with OAK) and is already carried by the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q96BI3 SUPPORTS TRANSFER Human APH1A APP-processing evidence transfers; the term is broader than the supported catabolic process. Proposed replacements: amyloid precursor protein catabolic process Supporting Evidence: PMID:20126630 gamma-Secretase is crucial for the generation of the neurotoxic amyloid beta-peptide (Abeta) PMID:20126630 In both cases, the APP intracellular domain (AICD) is released into the cytosol upon Ξ³-secretase cleavage. |
| GO:0042987 amyloid precursor protein catabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: APP catabolic process by gamma-secretase. Reason: Core: the Aph1a-containing complex cleaves APP C-terminal fragments to Abeta/p3 and AICD. Supporting Evidence: PMID:20126630 gamma-Secretase is crucial for the generation of the neurotoxic amyloid beta-peptide (Abeta) PMID:20126630 In both cases, the APP intracellular domain (AICD) is released into the cytosol upon Ξ³-secretase cleavage. |
| GO:0061133 endopeptidase activator activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Endopeptidase activator activity transferred from mouse/human; Aph1a is required for gamma-secretase activity. Reason: Aph1a is required for presenilin protease activity and the human and mouse donors carry experimental support, so the claim is defensible. But Aph1a is a constitutive non-catalytic subunit of the protease rather than an extrinsic activator; the core representation used here is protein-macromolecule adaptor activity plus contributes_to aspartic endopeptidase activity, intramembrane cleaving. Supporting Evidence: PMID:20145246 Gamma-secretase is a ubiquitous, multiprotein enzyme composed of presenilin, nicastrin, Aph-1, and Pen-2. PMID:20145246 Aph-1 residues His-171 and His-197 are involved in substrate binding. |
| GO:0061133 endopeptidase activator activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Endopeptidase activator activity transferred from mouse/human; Aph1a is required for gamma-secretase activity. Reason: Aph1a is required for presenilin protease activity and the human and mouse donors carry experimental support, so the claim is defensible. But Aph1a is a constitutive non-catalytic subunit of the protease rather than an extrinsic activator; the core representation used here is protein-macromolecule adaptor activity plus contributes_to aspartic endopeptidase activity, intramembrane cleaving. Supporting Evidence: PMID:20145246 Gamma-secretase is a ubiquitous, multiprotein enzyme composed of presenilin, nicastrin, Aph-1, and Pen-2. PMID:20145246 Aph-1 residues His-171 and His-197 are involved in substrate binding. |
| GO:0070765 gamma-secretase complex | IEA GO_REF:0000120 | ACCEPT | Summary: Aph1a is a core subunit of the gamma-secretase complex. Reason: Gamma-secretase is composed of presenilin, nicastrin, Aph-1 and Pen-2; Aph-1aL co-fractionates with the other components in rat brain. Supporting Evidence: PMID:20145246 Gamma-secretase is a ubiquitous, multiprotein enzyme composed of presenilin, nicastrin, Aph-1, and Pen-2. PMID:20126630 The Ξ³-sectretase components nicastrin, PS1-CTF, PS2-CTF, Aph-1aL and Pen-2 were enriched in fraction 5β7 of this gradient file:rat/Aph1a/Aph1a-uniprot.txt Component of the gamma-secretase complex. |
| GO:0070765 gamma-secretase complex | ISO GO_REF:0000121 | ACCEPT | Summary: Aph1a is a core subunit of the gamma-secretase complex. Reason: Gamma-secretase is composed of presenilin, nicastrin, Aph-1 and Pen-2; Aph-1aL co-fractionates with the other components in rat brain. Supporting Evidence: PMID:20145246 Gamma-secretase is a ubiquitous, multiprotein enzyme composed of presenilin, nicastrin, Aph-1, and Pen-2. PMID:20126630 The Ξ³-sectretase components nicastrin, PS1-CTF, PS2-CTF, Aph-1aL and Pen-2 were enriched in fraction 5β7 of this gradient file:rat/Aph1a/Aph1a-uniprot.txt Component of the gamma-secretase complex. |
| GO:0070765 gamma-secretase complex | ISO GO_REF:0000121 | ACCEPT | Summary: Aph1a is a core subunit of the gamma-secretase complex. Reason: Gamma-secretase is composed of presenilin, nicastrin, Aph-1 and Pen-2; Aph-1aL co-fractionates with the other components in rat brain. Supporting Evidence: PMID:20145246 Gamma-secretase is a ubiquitous, multiprotein enzyme composed of presenilin, nicastrin, Aph-1, and Pen-2. PMID:20126630 The Ξ³-sectretase components nicastrin, PS1-CTF, PS2-CTF, Aph-1aL and Pen-2 were enriched in fraction 5β7 of this gradient file:rat/Aph1a/Aph1a-uniprot.txt Component of the gamma-secretase complex. |
| GO:0070765 gamma-secretase complex | ISO GO_REF:0000121 | ACCEPT | Summary: Aph1a is a core subunit of the gamma-secretase complex. Reason: Gamma-secretase is composed of presenilin, nicastrin, Aph-1 and Pen-2; Aph-1aL co-fractionates with the other components in rat brain. Supporting Evidence: PMID:20145246 Gamma-secretase is a ubiquitous, multiprotein enzyme composed of presenilin, nicastrin, Aph-1, and Pen-2. PMID:20126630 The Ξ³-sectretase components nicastrin, PS1-CTF, PS2-CTF, Aph-1aL and Pen-2 were enriched in fraction 5β7 of this gradient file:rat/Aph1a/Aph1a-uniprot.txt Component of the gamma-secretase complex. |
| GO:0097060 synaptic membrane | IDA PMID:20126630 Synaptic and endosomal localization of active gamma-secretas... | KEEP AS NON CORE | Summary: Aph-1aL present in rat brain synaptic membrane fractions with high gamma-secretase activity. Reason: Direct rat-brain fractionation evidence; a peripheral neuronal location of the complex. Supporting Evidence: PMID:20126630 The Ξ³-secretase components were present in both the synaptic membrane and synaptic vesicle fractions, but the degree of enrichment varied between experiments. |
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Download this section (compressed HTML)Q: Should GO provide an informative MF term for substrate recruitment by non-catalytic intramembrane-protease subunits (Aph-1 binding of APP and Jagged CTFs), rather than leaving it as protein binding?
Q: Should the rat ISO transfer of endopeptidase activator activity to a constitutive gamma-secretase subunit be replaced by contributes_to aspartic endopeptidase activity, intramembrane cleaving?
Experiment: Knock down Aph1a versus Aph1b/Aph1c in rat primary neurons and quantify synaptic versus endosomal gamma-secretase activity (AICD, Abeta40/42) to test whether Aph1a-containing complexes account for the synaptic pool.
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