| http://purl.uniprot.org/citations/25043001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25043001 | http://www.w3.org/2000/01/rdf-schema#comment | "Hundreds of tail-anchored proteins, including soluble N-ethylmaleimide-sensitive factor attachment receptors (SNAREs) involved in vesicle fusion, are inserted post-translationally into the endoplasmic reticulum membrane by a dedicated protein-targeting pathway. Before insertion, the carboxy-terminal transmembrane domains of tail-anchored proteins are shielded in the cytosol by the conserved targeting factor Get3 (in yeast; TRC40 in mammals). The Get3 endoplasmic-reticulum receptor comprises the cytosolic domains of the Get1/2 (WRB/CAML) transmembrane complex, which interact individually with the targeting factor to drive a conformational change that enables substrate release and, as a consequence, insertion. Because tail-anchored protein insertion is not associated with significant translocation of hydrophilic protein sequences across the membrane, it remains possible that Get1/2 cytosolic domains are sufficient to place Get3 in proximity with the endoplasmic-reticulum lipid bilayer and permit spontaneous insertion to occur. Here we use cell reporters and biochemical reconstitution to define mutations in the Get1/2 transmembrane domain that disrupt tail-anchored protein insertion without interfering with Get1/2 cytosolic domain function. These mutations reveal a novel Get1/2 insertase function, in the absence of which substrates stay bound to Get3 despite their proximity to the lipid bilayer; as a consequence, the notion of spontaneous transmembrane domain insertion is a non sequitur. Instead, the Get1/2 transmembrane domain helps to release substrates from Get3 by capturing their transmembrane domains, and these transmembrane interactions define a bona fide pre-integrated intermediate along a facilitated route for tail-anchor entry into the lipid bilayer. Our work sheds light on the fundamental point of convergence between co-translational and post-translational endoplasmic-reticulum membrane protein targeting and insertion: a mechanism for reducing the ability of a targeting factor to shield its substrates enables substrate handover to a transmembrane-domain-docking site embedded in the endoplasmic-reticulum membrane."xsd:string |
| http://purl.uniprot.org/citations/25043001 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature13471"xsd:string |
| http://purl.uniprot.org/citations/25043001 | http://purl.uniprot.org/core/author | "Wang F."xsd:string |
| http://purl.uniprot.org/citations/25043001 | http://purl.uniprot.org/core/author | "Chan C."xsd:string |
| http://purl.uniprot.org/citations/25043001 | http://purl.uniprot.org/core/author | "Denic V."xsd:string |
| http://purl.uniprot.org/citations/25043001 | http://purl.uniprot.org/core/author | "Weir N.R."xsd:string |
| http://purl.uniprot.org/citations/25043001 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25043001 | http://purl.uniprot.org/core/name | "Nature"xsd:string |
| http://purl.uniprot.org/citations/25043001 | http://purl.uniprot.org/core/pages | "441-444"xsd:string |
| http://purl.uniprot.org/citations/25043001 | http://purl.uniprot.org/core/title | "The Get1/2 transmembrane complex is an endoplasmic-reticulum membrane protein insertase."xsd:string |
| http://purl.uniprot.org/citations/25043001 | http://purl.uniprot.org/core/volume | "512"xsd:string |
| http://purl.uniprot.org/citations/25043001 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25043001 |
| http://purl.uniprot.org/citations/25043001 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25043001 |
| http://purl.uniprot.org/uniprot/#_P63027-mappedCitation-25043001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25043001 |
| http://purl.uniprot.org/uniprot/#_A0A6A5PWT5-mappedCitation-25043001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25043001 |
| http://purl.uniprot.org/uniprot/#_A0A6A5PX83-mappedCitation-25043001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25043001 |
| http://purl.uniprot.org/uniprot/#_P49069-mappedCitation-25043001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25043001 |
| http://purl.uniprot.org/uniprot/#_P40056-mappedCitation-25043001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25043001 |
| http://purl.uniprot.org/uniprot/#_Q13190-mappedCitation-25043001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25043001 |
| http://purl.uniprot.org/uniprot/#_O00258-mappedCitation-25043001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25043001 |
| http://purl.uniprot.org/uniprot/#_P50402-mappedCitation-25043001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25043001 |
| http://purl.uniprot.org/uniprot/#_P51648-mappedCitation-25043001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25043001 |
| http://purl.uniprot.org/uniprot/#_Q12154-mappedCitation-25043001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25043001 |
| http://purl.uniprot.org/uniprot/#_Q16623-mappedCitation-25043001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25043001 |