ArticleThe Journal of biological chemistry2019
Proteomic discovery of substrates of the cardiovascular protease ADAMTS7.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Integrative transcriptomic analysis identifies ACP5 and FBLN5 as candidate shared transcriptomic signatures between pulpitis and carotid plaque rupture.Scientific reports · 2026Article
- Current Advances in the Physiological Roles and Disease-Associated Mechanisms of ADAMTS16.International journal of molecular sciences · 2026Review
- Proteolytic remodelling of the extracellular matrix by pericytes.The FEBS journal · 2026Review
- Deleterious variants in LTBP4 are associated with severe pediatric sepsis.Pediatric research · 2026Article
- LTBP4 deficiency inhibits NLRP3 inflammasome activation in cardiomyocytes and attenuates heart failure in male mice.Nature communications · 2026Article
- Review
- ADAMTS7 promotes smooth muscle foam cell expansion in atherosclerosis.The Journal of clinical investigation · 2026Article
- An Overview of ADAMTS Proteases.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Structure and Function of the Extracellular Matrix in Normal and Pathological Conditions: Looking at the Bicuspid Aortic Valve.International journal of molecular sciences · 2025Review
- Article
- ADAMTS7, a target in atherosclerosis, cooperates with its homolog ADAMTS12 to protect against myxomatous valve degeneration.Journal of molecular and cellular cardiology plus · 2025Article
- Cleavage of Cartilage Oligomeric Matrix Protein (COMP) by ADAMTS4 generates a neoepitope associated with osteoarthritis and other forms of degenerative joint disease.Matrix biology : journal of the International Society for Matrix Biology · 2025Article
- Design, synthesis and biological evaluation of arylsulfonamides as ADAMTS7 inhibitors.RSC medicinal chemistry · 2024Article
- ADAMTS-7 Modulates Atherosclerotic Plaque Formation by Degradation of TIMP-1.Circulation research · 2023Article
- ADAMTS7: a Novel Therapeutic Target in Atherosclerosis.Current atherosclerosis reports · 2023Review
- Phylogenetic inference of the emergence of sequence modules and protein-protein interactions in the ADAMTS-TSL family.PLoS computational biology · 2023Article
- Screening of hub inflammatory bowel disease biomarkers and identification of immune-related functions based on basement membrane genes.European journal of medical research · 2023Article
- ADAMTS-7 deficiency attenuates thoracic aortic aneurysm and dissection in mice.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Proteolysis: a key post-translational modification regulating proteoglycans.American journal of physiology. Cell physiology · 2022Review
- Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The protease ADAMTS7 functions in the extracellular matrix (ECM) of the cardiovascular system. However, its physiological substrate specificity and mechanism of regulation remain to be explored. To address this, we conducted an unbiased substrate analysis using terminal amine isotopic labeling of substrates (TAILS). The analysis identified candidate substrates of ADAMTS7 in the human fibroblast secretome, including proteins with a wide range of functions, such as collagenous and noncollagenous extracellular matrix proteins, growth factors, proteases, and cell-surface receptors. It also suggested that autolysis occurs at Glu-729-Val-730 and Glu-732-Ala-733 in the ADAMTS7 Spacer domain, which was corroborated by N-terminal sequencing and Western blotting. Importantly, TAILS also identified proteolysis of the latent TGF-β-binding proteins 3 and 4 (LTBP3/4) at a Glu-Val and Glu-Ala site, respectively. Using purified enzyme and substrate, we confirmed ADAMTS7-catalyzed proteolysis of recombinant LTBP4. Moreover, we identified multiple additional scissile bonds in an N-terminal linker region of LTBP4 that connects fibulin-5/tropoelastin and fibrillin-1-binding regions, which have an important role in elastogenesis. ADAMTS7-mediated cleavage of LTBP4 was efficiently inhibited by the metalloprotease inhibitor TIMP-4, but not by TIMP-1 and less efficiently by TIMP-2 and TIMP-3. As TIMP-4 expression is prevalent in cardiovascular tissues, we propose that TIMP-4 represents the primary endogenous ADAMTS7 inhibitor. In summary, our findings reveal LTBP4 as an ADAMTS7 substrate, whose cleavage may potentially impact elastogenesis in the cardiovascular system. We also identify TIMP-4 as a likely physiological ADAMTS7 inhibitor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.