| http://purl.uniprot.org/citations/22566642 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22566642 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22566642 | http://www.w3.org/2000/01/rdf-schema#comment | "Our knowledge of the O-glycoproteome [N-acetylgalactosamine (GalNAc) type] is highly limited. The O-glycoproteome is differentially regulated in cells by dynamic expression of a subset of 20 polypeptide GalNAc-transferases (GalNAc-Ts), and methods to identify important functions of individual GalNAc-Ts are largely unavailable. We recently introduced SimpleCells, i.e., human cell lines made deficient in O-glycan extension by zinc finger nuclease targeting of a key gene in O-glycan elongation (Cosmc), which allows for proteome-wide discovery of O-glycoproteins. Here we have extended the SimpleCell concept to include proteome-wide discovery of unique functions of individual GalNAc-Ts. We used the GalNAc-T2 isoform implicated in dyslipidemia and the human HepG2 liver cell line to demonstrate unique functions of this isoform. We confirm that GalNAc-T2-directed site-specific O-glycosylation inhibits proprotein activation of the lipase inhibitor ANGPTL3 in HepG2 cells and further identify eight O-glycoproteins exclusively glycosylated by T2 of which one, ApoC-III, is implicated in dyslipidemia. Our study supports an essential role for GalNAc-T2 in lipid metabolism, provides serum biomarkers for GalNAc-T2 enzyme function, and validates the use of GALNT gene targeting with SimpleCells for broad discovery of disease-causing deficiencies in O-glycosylation. The presented glycoengineering strategy opens the way for proteome-wide discovery of functions of GalNAc-T isoforms and their role in congenital diseases and disorders."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1203563109"xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1203563109"xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Kong Y."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Kong Y."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Bennett E.P."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Bennett E.P."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Clausen H."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Clausen H."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Levery S.B."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Levery S.B."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Pedersen N.B."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Pedersen N.B."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Vakhrushev S.Y."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Vakhrushev S.Y."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Mandel U."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Mandel U."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Nudelman A.S."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Nudelman A.S."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Schjoldager K.T."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Schjoldager K.T."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Steentoft C."xsd:string |
| http://purl.uniprot.org/citations/22566642 | http://purl.uniprot.org/core/author | "Steentoft C."xsd:string |