PXD028825-1

PXD028825 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-29 00:13:35	ID requested
⏵ 1	2022-03-17 03:02:39	announced

Dataset with its publication pending

submitter keyword: Type 1 diabetes, post-translational modifications, glucokinase

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

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PRIDE project URI

• PRIDE
  1. PXD028825
     1. Label: PRIDE project
     2. Name: Citrullination of glucokinase is linked to autoimmune diabetes