Aarhus Universitets segl

English

Du er her: AU » Om AU » Organisation » Bioinformatic prediction of putative conveyers of O-GlcNA...

Om AU

Bioinformatic prediction of putative conveyers of O-GlcNAc Transferase intellectual disability

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

DOI

Protein O-GlcNAcylation is a dynamic posttranslational modification that is catalyzed by the enzyme O-GlcNAc transferase (OGT) and is essential for neurodevelopment and postnatal neuronal function. Missense mutations in OGT segregate with a novel X-linked intellectual disability syndrome, the OGT congenital disorder of glycosylation (OGT-CDG). One hypothesis for the etiology of OGT-CDG is that loss of OGT activity leads to hypo-O-GlcNAcylation of as yet unidentified, specific neuronal proteins, affecting essential embryonic, and postnatal neurodevelopmental processes; however, the identity of these O-GlcNAcylated proteins is not known. Here, we used bioinformatic techniques to integrate sequence conservation, structural data, clinical data, and the available literature to identify 22 candidate proteins that convey OGT-CDG. We found using gene ontology and PANTHER database data that these candidate proteins are involved in diverse processes including Ras/MAPK signaling, translational repression, cytoskeletal dynamics, and chromatin remodeling. We also identify pathogenic missense variants at O-GlcNAcylation sites that segregate with intellectual disability. This work establishes a preliminary platform for the mechanistic dissection of the links between protein O-GlcNAcylation and neurodevelopment in OGT-CDG.

OriginalsprogEngelsk
Artikelnummer102276
TidsskriftThe Journal of Biological Chemistry
Vol/bind298
Nummer9
Antal sider13
ISSN0021-9258
DOI
StatusUdgivet - sep. 2022

Bibliografisk note

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Se relationer på Aarhus Universitet Citationsformater

ID: 279443102