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PXD054339-1

PXD054339 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleN-terminomics and proteomics analysis of Calpain-2 reveal key proteolytic processing of metabolic and cell adhesion proteins
DescriptionAberrant levels of the cysteine protease Calpain-2 have been linked to neurodegeneration, inflammation, and cancer, yet our understanding of this protease and its substrates remains limited. Systematic studies to identify Calpain-2 substrates have been largely confined to peptide libraries or in vitro studies, which fail to represent physiological cellular conditions and physiologically relevant substrates. In addition to Calpain-2, Calpain-1 is also ubiquitously present in cells, making it challenging to understand the distinct contributions of Calpain-1 and Calpain-2 in cells and the difference between their substrates’ repertoires. We used a genetic approach to knockout Calpain-2 in the THP-1 human monocyte-like cells, followed by proteomic and N-terminomic/TAILS mass spectrometry approaches to identify Calpain-2 substrates. We identified 51 new putative Calpain-2 substrates. The direct cleavage of selected substrates by Calpain-2 was confirmed using in vitro assays. Metabolomics was performed and identified a role for Calpain-2 in the regulation of pyrimidine and glutathione metabolism. Our unbiased and quantitative mass spectrometry analytical pipeline provides new evidence on the physiological functions of Calpain-2 and its newly identified substrates in THP-1 cells.
HostingRepositoryPRIDE
AnnounceDate2025-04-25
AnnouncementXMLSubmission_2025-04-25_12:06:03.161.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLuiz Gustavo de Almeida
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-07-29 05:22:25ID requested
12025-04-25 12:06:03announced
Publication List
10.1002/PRO.70144;
Keyword List
submitter keyword: Metabolism,Calpain-2, Protease, Proteomics, N-terminomics, THP-1 monocyte
Contact List
Antoine Dufour
contact affiliationDepartment of Biochemistry and Molecular Biology, University of Calgary, Alberta, Canada; Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada; The Hotchkiss Brain Institute, University of Calgary, Alberta, Canada; McCaig Institute for Bone and Joint Health, University of Calgary, Alberta, Canada
contact emailantoine.dufour@ucalgary.ca
lab head
Luiz Gustavo de Almeida
contact affiliationUniversity of Calgary
contact emailluizgustavo.biotec@hotmail.com
dataset submitter
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Dataset FTP location
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