PXD004754

PXD004754 is an original dataset announced via ProteomeXchange.

Title	Identification of novel natural substrates of fibroblast activation protein by differential degradomics and proteomics
Description	Fibroblast Activation Protein (FAP) is a cell-surface transmembrane-anchored anchored dimeric protease. This unique constitutively active serine protease has both dipeptidyl aminopeptidase and endopeptidase activities, and can hydrolyse post-proline bonds. FAP expression is very low in adult organs, but is greatly up regulated by activated fibroblasts in sites of tissue remodelling, including fibrosis, atherosclerosis, arthritis and tumours. Primary mouse embryonic fibroblasts (MEF) were isolated from FAP gene knockout (GKO) embryos, immortalised and then transduced to express either enzyme active or inactive FAP. The cell secretomes were analysed using degradomic and proteomic techniques. Terminal Amine Isotopic Labelling of Substrates based degradomics identified cleavage sites in collagens, many other extracellular matrix (ECM) and associated proteins, and lysyl oxidase-like-1, CCL2, IL13, C1qT6 and CSF-1 that were confirmed in vitro. In addition, differential metabolic labelling coupled with quantitative proteomic analysis also implicated FAP in ECM-cell interactions, as well as with coagulation and wound healing associated proteins. FAP GKO plasma exhibited slower that wildtype clotting times. This study greatly enhances the understanding of the roles of FAP through a significant expansion of the substrate repertoire of this protease and identifying downstream effects of its activity that support roles in pathological processes.
HostingRepository	PRIDE
AnnounceDate	2018-12-19
AnnouncementXML	Submission_2018-12-19_00:47:20.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Oliver Schilling
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	QSTAR

Revision	Datetime	Status	ChangeLog Entry
0	2016-08-10 07:56:30	ID requested
⏵ 1	2018-12-19 00:47:21	announced

Zhang HE, Hamson EJ, Koczorowska MM, Tholen S, Chowdhury S, Bailey CG, Lay AJ, Twigg SM, Lee Q, Roediger B, Biniossek ML, O'Rourke MB, McCaughan GW, Keane FM, Schilling O, Gorrell MD, Identification of Novel Natural Substrates of Fibroblast Activation Protein-alpha by Differential Degradomics and Proteomics. Mol Cell Proteomics, 18(1):65-85(2019) [pubmed]

curator keyword: Biological

submitter keyword: Protease

Oliver Schilling
contact affiliation	Institute of Molecular Medicine and Cell Research University of Freiburg Stefan-Meier-Str. 17 D-79104 Freiburg, Germany
contact email	oliver.schilling@mol-med.uni-freiburg.de
lab head
Oliver Schilling
contact affiliation	University of Freiburg
contact email	oliver.schilling@mol-med.uni-freiburg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD004754
     1. Label: PRIDE project
     2. Name: Identification of novel natural substrates of fibroblast activation protein by differential degradomics and proteomics