PXD028825 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Citrullination of glucokinase is linked to autoimmune diabetes |
Description | Inflammation, including reactive oxygen species and inflammatory cytokines in tissues amplify various post-translational modifications (PTMs) of self-proteins. A number of PTMs have been identified as autoimmune biomarkers in the initiation and progression of Type 1 diabetes (T1D). In this study, we have identified the citrullination of pancreatic glucokinase (GK) as a result of inflammation, triggering autoimmunity and affecting GK biological functions. Glucokinase is expressed in hepatocytes to regulate glycogen synthesis, and in pancreatic beta cells as a glucose sensor to initiate glycolysis and insulin signaling. We identify autoantibodies and autoreactive CD4+ T cells to glucokinase epitopes in the circulation of T1D patients and NOD mice. Finally, citrullination alters GK biologic activity (Km) and suppresses glucose-stimulated insulin secretion. Our studies define glucokinase as a T1D biomarker, providing new insights of how inflammation drives PTMs to create both neoautoantigens and affect beta cell metabolism. |
HostingRepository | PRIDE |
AnnounceDate | 2022-03-17 |
AnnouncementXML | Submission_2022-03-17_03:02:38.943.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | TuKiet Lam |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue; deamidated residue; L-citrulline |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-09-29 00:13:35 | ID requested | |
⏵ 1 | 2022-03-17 03:02:39 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Type 1 diabetes, post-translational modifications, glucokinase |
Contact List
TuKiet Lam |
contact affiliation | Yale University Department of Molecular Biophysics and Biochemistry |
contact email | tukiet.lam@yale.edu |
lab head | |
TuKiet Lam |
contact affiliation | Yale University |
contact email | tukiet.lam@yale.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD028825
- Label: PRIDE project
- Name: Citrullination of glucokinase is linked to autoimmune diabetes