| http://purl.uniprot.org/citations/35666870 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35666870 | http://www.w3.org/2000/01/rdf-schema#comment | "Human pancreatic islets highly express CD59, which is a glycosylphosphatidylinositol (GPI)-anchored cell-surface protein and is required for insulin secretion. How cell-surface CD59 could interact with intracellular exocytotic machinery has so far not been described. We now demonstrate the existence of CD59 splice variants in human pancreatic islets, which have unique C-terminal domains replacing the GPI-anchoring signal sequence. These isoforms are found in the cytosol of β-cells, interact with SNARE proteins VAMP2 and SNAP25, colocalize with insulin granules, and rescue insulin secretion in CD59-knockout (KO) cells. We therefore named these isoforms IRIS-1 and IRIS-2 (Isoforms Rescuing Insulin Secretion 1 and 2). Antibodies raised against each isoform revealed that expression of both IRIS-1 and IRIS-2 is significantly lower in islets isolated from human type 2 diabetes (T2D) patients, as compared to healthy controls. Further, glucotoxicity induced in primary, healthy human islets led to a significant decrease of IRIS-1 expression, suggesting that hyperglycemia (raised glucose levels) and subsequent decreased IRIS-1 expression may contribute to relative insulin deficiency in T2D patients. Similar isoforms were also identified in the mouse CD59B gene, and targeted CRISPR/Cas9-mediated knockout showed that these intracellular isoforms, but not canonical CD59B, are involved in insulin secretion from mouse β-cells. Mouse IRIS-2 is also down-regulated in diabetic db/db mouse islets. These findings establish the endogenous existence of previously undescribed non–GPI-anchored intracellular isoforms of human CD59 and mouse CD59B, which are required for normal insulin secretion."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.2120083119"xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/author | "Blom A.M."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/author | "Villoutreix B.O."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/author | "King B.C."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/author | "Wozniak K."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/author | "Lund P.E."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/author | "Noga M."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/author | "Korsgren O."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/author | "Barg S."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/author | "Renstrom E."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/author | "Krus U."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/author | "Golec E."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/author | "Omar-Hmeadi M."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/author | "Ekstrom A."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/pages | "e2120083119"xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/title | "Alternative splicing encodes functional intracellular CD59 isoforms that mediate insulin secretion and are down-regulated in diabetic islets."xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://purl.uniprot.org/core/volume | "119"xsd:string |
| http://purl.uniprot.org/citations/35666870 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/35666870 |
| http://purl.uniprot.org/citations/35666870 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/35666870 |
| http://purl.uniprot.org/uniprot/#_P13987-mappedCitation-35666870 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35666870 |
| http://purl.uniprot.org/uniprot/#_A0A3G2LMJ8-mappedCitation-35666870 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35666870 |