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PXD028825

PXD028825 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCitrullination of glucokinase is linked to autoimmune diabetes
DescriptionInflammation, 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.
HostingRepositoryPRIDE
AnnounceDate2022-03-17
AnnouncementXMLSubmission_2022-03-17_03:02:38.943.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTuKiet Lam
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue; deamidated residue; L-citrulline
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-09-29 00:13:35ID requested
12022-03-17 03:02:39announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Type 1 diabetes, post-translational modifications, glucokinase
Contact List
TuKiet Lam
contact affiliationYale University Department of Molecular Biophysics and Biochemistry
contact emailtukiet.lam@yale.edu
lab head
TuKiet Lam
contact affiliationYale University
contact emailtukiet.lam@yale.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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