PXD054339

PXD054339 is an original dataset announced via ProteomeXchange.

Title	N-terminomics and proteomics analysis of Calpain-2 reveal key proteolytic processing of metabolic and cell adhesion proteins
Description	Aberrant 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.
HostingRepository	PRIDE
AnnounceDate	2025-04-25
AnnouncementXML	Submission_2025-04-25_12:06:03.161.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luiz Gustavo de Almeida
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-29 05:22:25	ID requested
⏵ 1	2025-04-25 12:06:03	announced

10.1002/PRO.70144;

submitter keyword: Metabolism,Calpain-2, Protease, Proteomics, N-terminomics, THP-1 monocyte

Antoine Dufour
contact affiliation	Department 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 email	antoine.dufour@ucalgary.ca
lab head
Luiz Gustavo de Almeida
contact affiliation	University of Calgary
contact email	luizgustavo.biotec@hotmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/04/PXD054339

PRIDE project URI

• PRIDE
  1. PXD054339
     1. Label: PRIDE project
     2. Name: N-terminomics and proteomics analysis of Calpain-2 reveal key proteolytic processing of metabolic and cell adhesion proteins