| http://purl.uniprot.org/citations/28302723 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28302723 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28302723 | http://www.w3.org/2000/01/rdf-schema#comment | "O-GlcNAc is a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription. In humans, single genes encode enzymes for its attachment (O-GlcNAc transferase (OGT)) and removal (O-GlcNAcase (OGA)). An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family. A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments. Recombinant expression of L254F-OGT demonstrated that the enzyme is active as both a glycosyltransferase and an HCF-1 protease. Despite the reduction in OGT levels seen in the L254F-OGT individual cells, we observed that steady-state global O-GlcNAc levels remained grossly unaltered. Surprisingly, lymphoblastoids from affected individuals displayed a marked decrease in steady-state OGA protein and mRNA levels. We observed an enrichment of the OGT-containing transcriptional repressor complex mSin3A-HDAC1 at the proximal promoter region of OGA and correspondingly decreased OGA promoter activity in affected cells. Global transcriptome analysis of L254F-OGT lymphoblastoids compared with controls revealed a small subset of genes that are differentially expressed. Thus, we have begun to unravel the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism, albeit imperfect, given the phenotype of affected individuals, to maintain steady-state O-GlcNAc levels. Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m116.771030"xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m116.771030"xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Patel S."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Patel S."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Wang T."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Wang T."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Shaw M."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Shaw M."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Schwartz C."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Schwartz C."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Wells L."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Wells L."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Peng Y."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Peng Y."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Viskochil D."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Viskochil D."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Carey J."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Carey J."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Gecz J."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "Gecz J."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "May M."xsd:string |
| http://purl.uniprot.org/citations/28302723 | http://purl.uniprot.org/core/author | "May M."xsd:string |