PXD027724

PXD027724 is an original dataset announced via ProteomeXchange.

Title	Post-translational regulation and proteolytic activity of human adamts-8: a comparison with adamts-1, -4, and -5
Description	A Disintegrin-like And Metalloprotease with Thrombospondin type 1 motifs (ADAMTS)-8 is a secreted protease which has been recently implicated in the pathogenesis of pulmonary arterial hypertension (PAH). However, the substrate repertoire of ADAMTS-8 and regulation of its activity are incompletely understood. Although considered a proteoglycanase because of high sequence similarity and close phylogenetic relationship to the proteoglycan-degrading proteases ADAMTS-1, -4, -5 and -15, as well as tight genetic linkage with ADAMTS-15 on human chromosome 11, its aggrecanase activity was reported to be weak. A number of post-translational modifications regulate ADAMTS proteases such as autolysis, inhibition by endogenous inhibitors and receptor-mediated endocytosis, but their impact on ADAMTS-8 is unknown. Here, we show that ADAMTS-8 undergoes autolysis at six different sites within its spacer domain. We also found that ADAMTS-8 cleaves osteopontin, a phosphoprotein whose expression is upregulated in PAH. Multiple ADAMTS-8 cleavage sites were identified using liquid chromatography- tandem mass spectrometry. Osteopontin cleavage by ADAMTS-8 is efficiently inhibited by TIMP-3, an endogenous inhibitor of ADAMTS-1, -4 and -5, as well as TIMP-2, which has no reported inhibitory activity against other ADAMTS family members. These differences in post-translational regulation and substrate repertoire differentiate ADAMTS-8 from other family members and may help to elucidate its role in PAH.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_05:58:01.163.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD027724
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Daniel Martin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-05 08:58:14	ID requested
⏵ 1	2022-02-17 05:58:01	announced

Santamaria S, Martin DR, Dong X, Yamamoto K, Apte SS, Ahnstr, ö, m J, Post-translational regulation and proteolytic activity of the metalloproteinase ADAMTS8. J Biol Chem, 297(5):101323(2021) [pubmed]

submitter keyword: ADAMTS, protease, ECM, PAH, OPN

Suneel Apte
contact affiliation	Biomedical engineering, Lerner research institue, Cleveland Clinic, Cleveland, OH, USA
contact email	aptes@ccf.org
lab head
Daniel Martin
contact affiliation	Cleveland Clinic
contact email	martin32@mail.usf.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027724
     1. Label: PRIDE project
     2. Name: Post-translational regulation and proteolytic activity of human adamts-8: a comparison with adamts-1, -4, and -5