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PXD055223-2

PXD055223 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDevelopment of a proteomic workflow for the identification of heparan sulfate proteoglycan-binding substrates of ADAM17
DescriptionEctodomain shedding, which is the proteolytic release of transmembrane proteins from the cell surface, is crucial for cell-to-cell communication and other biological processes. The metalloproteinase ADAM17 mediates ectodomain shedding of over 50 transmembrane proteins ranging from cytokines and growth factors, such as TNF and EGFR ligands, to signaling receptors and adhesion molecules. Yet, the ADAM17 sheddome is only partly defined and biological functions of the protease have not been fully characterized. Some ADAM17 substrates (e.g. HB-EGF) are known to bind to heparan sulfate proteoglycans (HSPG), and we hypothesised that such substrates would be under-represented in traditional secretome analyses, due to their binding to cell surface or pericellular HSPGs. Thus, to identify novel HSPG-binding ADAM17 substrates, we developed a proteomic workflow that involves addition of heparin to solubilize HSPG-binding proteins from the cell layer, thereby allowing their mass spectrometry detection by heparin-secretome (HEP-SEC) analysis. Applying this methodology to murine embryonic fibroblasts stimulated with an ADAM17 activator enabled us to identify 47 transmembrane proteins that were shed in response to ADAM17 activation. This included known HSPG-binding ADAM17 substrates (i.e. HB-EGF, CX3CL1) and 14 novel HSPG-binding putative ADAM17 substrates.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_07:02:07.878.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterStephan Mueller
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-08-27 01:47:23ID requested
12024-10-15 11:17:22announced
22024-10-22 07:02:08announced2024-10-22: Updated project metadata.
Publication List
10.1002/pmic.202400076;
Calligaris M, Span, ò DP, Puccio MC, M, ü, ller SA, Bonelli S, Lo Pinto M, Zito G, Blobel CP, Lichtenthaler SF, Troeberg L, Scilabra SD, Development of a Proteomic Workflow for the Identification of Heparan Sulphate Proteoglycan-Binding Substrates of ADAM17. Proteomics, ():e202400076(2024) [pubmed]
Keyword List
submitter keyword: ADAM17, ectodomain shedding, mouse, hepSEC, secretome, metalloproteases
Contact List
Dr Simone Dario Scilabra
contact affiliationProteomics group, Ri.MED Foundation, Palermo, Italy
contact emailsdscilabra@fondazionerimed.com
lab head
Stephan Mueller
contact affiliationDZNE Munich Neuroproteomics
contact emailstephan.mueller@dzne.de
dataset submitter
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Dataset FTP location
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