| http://purl.uniprot.org/citations/20145246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20145246 | http://www.w3.org/2000/01/rdf-schema#comment | "Gamma-secretase is a ubiquitous, multiprotein enzyme composed of presenilin, nicastrin, Aph-1, and Pen-2. It mediates the intramembrane proteolysis of many type 1 proteins, plays an essential role in numerous signaling pathways, and helps drive the pathogenesis of Alzheimer disease by excising the hydrophobic, aggregation-prone amyloid beta-peptide from the beta-amyloid precursor protein. A central unresolved question is how its many substrates bind and enter the gamma-secretase complex. Here, we provide evidence that both the beta-amyloid precursor protein holoprotein and its C-terminal fragments, the immediate substrates of gamma-secretase, can associate with Aph-1 at overexpressed as well as endogenous protein levels. This association was observed using bi-directional co-immunoprecipitation in multiple systems and detergent conditions, and an beta-amyloid precursor protein-Aph-1 complex was specifically isolated following in situ cross-linking in living cells. In addition, another endogenous canonical gamma-substrate, Jagged, showed association of both its full-length and C-terminal fragment forms with Aph-1. We were also able to demonstrate that this interaction with substrates was conserved across the multiple isoforms of Aph-1 (beta, alphaS, and alphaL), as they were all able to bind beta-amyloid precursor protein with similar affinity. Finally, two highly conserved intramembrane histidines (His-171 and His-197) within Aph-1, which were recently shown to be important for gamma-secretase activity, are required for efficient binding of substrates. Taken together, our data suggest a dominant role for Aph-1 in interacting with gamma-secretase substrates prior to their processing by the proteolytic complex."xsd:string |
| http://purl.uniprot.org/citations/20145246 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.088815"xsd:string |
| http://purl.uniprot.org/citations/20145246 | http://purl.uniprot.org/core/author | "Selkoe D.J."xsd:string |
| http://purl.uniprot.org/citations/20145246 | http://purl.uniprot.org/core/author | "LaVoie M.J."xsd:string |
| http://purl.uniprot.org/citations/20145246 | http://purl.uniprot.org/core/author | "Ostaszewski B.L."xsd:string |
| http://purl.uniprot.org/citations/20145246 | http://purl.uniprot.org/core/author | "Guo L.Y."xsd:string |
| http://purl.uniprot.org/citations/20145246 | http://purl.uniprot.org/core/author | "Chen A.C."xsd:string |
| http://purl.uniprot.org/citations/20145246 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20145246 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/20145246 | http://purl.uniprot.org/core/pages | "11378-11391"xsd:string |
| http://purl.uniprot.org/citations/20145246 | http://purl.uniprot.org/core/title | "Aph-1 associates directly with full-length and C-terminal fragments of gamma-secretase substrates."xsd:string |
| http://purl.uniprot.org/citations/20145246 | http://purl.uniprot.org/core/volume | "285"xsd:string |
| http://purl.uniprot.org/citations/20145246 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20145246 |
| http://purl.uniprot.org/citations/20145246 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/20145246 |
| http://purl.uniprot.org/uniprot/#_A0A0A0MRG2-mappedCitation-20145246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20145246 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JF05-mappedCitation-20145246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20145246 |
| http://purl.uniprot.org/uniprot/#_A0A140VJC8-mappedCitation-20145246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20145246 |
| http://purl.uniprot.org/uniprot/#_A0A218KGR2-mappedCitation-20145246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20145246 |
| http://purl.uniprot.org/uniprot/#_A0A8F9R5D5-mappedCitation-20145246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20145246 |
| http://purl.uniprot.org/uniprot/#_A0A8I6ASU4-mappedCitation-20145246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20145246 |
| http://purl.uniprot.org/uniprot/#_A0A2I3BPT1-mappedCitation-20145246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20145246 |
| http://purl.uniprot.org/uniprot/#_A0A2I3BQZ9-mappedCitation-20145246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20145246 |
| http://purl.uniprot.org/uniprot/#_A0A2I3BR03-mappedCitation-20145246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20145246 |
| http://purl.uniprot.org/uniprot/#_B4DGD0-mappedCitation-20145246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20145246 |