Affinage

ADAMTS1

A disintegrin and metalloproteinase with thrombospondin motifs 1 · UniProt Q9UHI8

Length
967 aa
Mass
105.4 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADAMTS1 is a secreted zinc metalloprotease that functions as a major extracellular matrix remodeling enzyme regulating angiogenesis, tissue morphogenesis, and proteoglycan turnover. Secreted as a latent proenzyme, it undergoes furin-mediated prodomain cleavage in the Golgi to yield the active p87 form, which anchors to the ECM via C-terminal thrombospondin type I motifs and a spacer region through heparan sulfate interactions; secondary cleavage by MMPs generates a p65 form with reduced anti-angiogenic capacity (PMID:9593739, PMID:10944521, PMID:15184385). Its catalytic activity cleaves proteoglycans (aggrecan at Glu-X sites, versican at >20 sites), basement membrane nidogens, syndecan-4, semaphorin 3C, NOTCH1, and EGF-like ligand precursors (HB-EGF, amphiregulin), thereby controlling processes from ovulation and cardiac trabeculation to satellite cell activation and bone metastasis (PMID:12054629, PMID:34450332, PMID:18775505, PMID:28939843, PMID:18267097, PMID:19608765). Independent of catalysis, its C-terminal domain sequesters VEGF165 and VEGFC to block VEGFR2/VEGFR3 signaling and inhibit angiogenesis and lymphangiogenesis, and haploinsufficiency in mice causes thoracic aortic aneurysm through a NOS2-dependent mechanism (PMID:12716911, PMID:24631293, PMID:28067899).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Establishing how ADAMTS1 is retained in the extracellular space resolved a basic question about its localization: the C-terminal TSP motifs and spacer region mediate ECM anchoring through sulfated glycosaminoglycan interactions.

    Evidence Deletion mutant analysis and heparin displacement in COS-7 cells

    PMID:9593739

    Open questions at the time
    • Specific GAG-binding residues not mapped
    • In vivo ECM anchoring not demonstrated
  2. 1999 High

    Demonstrating that recombinant ADAMTS1 suppresses FGF-2- and VEGF-induced angiogenesis with endothelial specificity established it as an anti-angiogenic factor, raising the question of mechanism.

    Evidence Cornea pocket assay, chorioallantoic membrane assay, endothelial proliferation assay with purified protein

    PMID:10438512

    Open questions at the time
    • Mechanism of endothelial specificity unknown
    • Whether catalytic activity was required not tested
  3. 2000 High

    Identification of two sequential processing steps — furin cleavage of the prodomain and MMP-mediated removal of C-terminal TSP repeats — explained how ADAMTS1 transitions from latent to active forms and how its anti-angiogenic potency is modulated post-secretion.

    Evidence In vitro reconstitution with purified furin and MMPs, furin and MMP inhibitors

    PMID:10944521

    Open questions at the time
    • Physiological context of MMP cleavage not established
    • Processing kinetics in vivo unknown
  4. 2000 High

    Knockout mouse phenotyping revealed essential in vivo roles in female fertility (ovulatory failure), growth, and organ morphogenesis, and identified progesterone receptor as a transcriptional regulator in granulosa cells.

    Evidence ADAMTS-1-null and PR-null mouse models, Northern blot, histology, fertility assays

    PMID:10781075 PMID:10811842 PMID:14668204

    Open questions at the time
    • Specific ovulatory substrates not yet identified
    • Mechanism of renal and adrenal phenotypes unclear
  5. 2002 High

    In vitro reconstitution with active-site mutants classified ADAMTS1 as a bona fide aggrecanase and showed its catalytic activity is zinc-dependent, latency is prodomain-conferred, and it is inhibited by TIMP-2 and TIMP-3.

    Evidence Purified aggrecan cleavage, zinc-binding domain point mutagenesis, TIMP inhibition assay

    PMID:12054629

    Open questions at the time
    • Relative contribution versus ADAMTS4/5 in cartilage not resolved
    • No in vivo aggrecanase role demonstrated
  6. 2003 High

    Two advances addressed the anti-angiogenic mechanism and the ovulatory substrate: ADAMTS1 sequesters VEGF165 via its C-terminal domain blocking VEGFR2 phosphorylation, and it cleaves versican in the cumulus-oocyte complex, linking its protease activity to ovulation.

    Evidence Co-IP, cross-linking, VEGFR2 phosphorylation assay; anti-neoepitope versican detection in PRKO ovaries

    PMID:12716911 PMID:12907688

    Open questions at the time
    • Whether VEGF sequestration and protease activity are independent anti-angiogenic mechanisms not resolved
    • Full set of ovulatory substrates unknown
  7. 2004 High

    Detailed mapping of furin cleavage at Arg235 in the Golgi and identification of conserved prodomain residues essential for biosynthesis refined the activation mechanism, while promoter dissection revealed LH/cAMP and PR act as cooperative transcriptional regulators through non-canonical binding sites.

    Evidence Site-directed mutagenesis with Brefeldin A/monensin in HEK293; promoter-reporter assays in primary granulosa cells

    PMID:15184385 PMID:15256533

    Open questions at the time
    • Prodomain chaperone function not structurally explained
    • Whether PR acts as direct DNA-binder or coregulator not definitively resolved
  8. 2006 High

    Expanding the substrate repertoire to nidogens, syndecan-4 ectodomain, EGF-like ligands, and TFPI-2 revealed ADAMTS1 as a broad ECM and cell-surface sheddase, while in vivo studies showed its catalytic activity promotes metastasis through EGFR/ErbB2 activation and is required for ovarian basement membrane integrity and lymphangiogenesis.

    Evidence DIGE proteomics, Y2H screen, catalytically dead mutant in metastasis model, ADAMTS1-null ovarian histology

    PMID:16314835 PMID:16511810 PMID:16641089 PMID:17097630

    Open questions at the time
    • Relative importance of individual substrates in each tissue context unclear
    • Anti- vs pro-metastatic roles appear context-dependent and unresolved
  9. 2007 High

    Crystal structures of the catalytic and disintegrin-like domains revealed a distinctive large S1' pocket, double calcium-binding site, and stacking of the disintegrin-like domain against the active site, providing the first structural framework for understanding substrate selectivity.

    Evidence X-ray crystallography with and without marimastat inhibitor

    PMID:17897672

    Open questions at the time
    • No structure of TSP/spacer domains
    • Structural basis of substrate discrimination versus ADAMTS4/5 not resolved
  10. 2008 High

    Genetic epistasis in mice established that endocardial Brg1 represses ADAMTS1 to preserve cardiac jelly for trabeculation, demonstrating a chromatin-level control mechanism for ADAMTS1 in cardiac development.

    Evidence Endocardium-specific Brg1 knockout rescued by ADAMTS1 deletion

    PMID:18267097

    Open questions at the time
    • Direct Brg1-ADAMTS1 promoter interaction not shown
    • Cardiac jelly substrates of ADAMTS1 not identified
  11. 2009 High

    Identification of HIF-1 as a direct transcriptional activator (by ChIP) in hypoxic endothelium added a third transcriptional axis, while paracrine EGF-like ligand shedding was shown to drive osteolytic bone metastasis by suppressing osteoblast OPG.

    Evidence ChIP for HIF-1, PI3K inhibitor, endothelial migration assay; bone metastasis model with EGFR inhibitor

    PMID:19349275 PMID:19608765

    Open questions at the time
    • Integration of HIF-1, PR, and Brg1 transcriptional programs in same tissue not studied
    • Whether shedding activity is substrate-selective in bone unclear
  12. 2014 Medium

    Extending the VEGF sequestration model to VEGFC/VEGFR3 in lymphatic endothelial cells explained the lymphangiogenic defect observed in null mice and broadened the anti-angiogenic mechanism to lymphatic vessels.

    Evidence Co-IP of ADAMTS1-VEGFC complex, VEGFR3 phosphorylation and tube formation assays in HMVEC-dLy

    PMID:24631293

    Open questions at the time
    • Domain requirements for VEGFC binding not mapped
    • In vivo VEGFC sequestration not directly demonstrated
  13. 2016 High

    ADAMTS1's metalloprotease activity was shown to regulate adipogenesis through ECM remodeling and FAK-ERK signaling, with adipose-specific knockout increasing fat mass, establishing a metabolic role beyond vascular and reproductive biology.

    Evidence Catalytically inactive mutant, adipogenesis assay, adipose-specific conditional KO mouse

    PMID:27447109

    Open questions at the time
    • Specific ECM substrates mediating adipogenesis suppression not identified
    • Whether FAK-ERK activation is direct or secondary to ECM changes unknown
  14. 2017 High

    Two landmark studies revealed that ADAMTS1 haploinsufficiency causes thoracic aortic aneurysm through NOS2 upregulation (rescuable by NOS2 inhibition), and that macrophage-released ADAMTS1 activates satellite cells by cleaving NOTCH1, connecting the protease to both vascular disease and muscle regeneration.

    Evidence Adamts1 haploinsufficient × Nos2 KO genetic epistasis with pharmacological rescue; macrophage-specific overexpression with Notch signaling assays

    PMID:28067899 PMID:28939843

    Open questions at the time
    • How ADAMTS1 haploinsufficiency leads to NOS2 upregulation mechanistically unresolved
    • Whether NOTCH1 is cleaved at a specific site by ADAMTS1 not mapped
  15. 2021 High

    Quantitative proteomics identified >20 novel cleavage sites in versican V1 and established a shared P1-Glu preference among ADAMTS1/4/5, providing a comprehensive cleavage map for the primary proteoglycan substrate.

    Evidence Label-free LC-MS/MS comparing active versus catalytically inactive ADAMTS1 digests of recombinant versican

    PMID:34450332

    Open questions at the time
    • Physiological relevance of individual cleavage sites not determined
    • Whether all sites are cleaved in vivo unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for substrate selectivity (no full-length structure exists), how the protease-dependent and VEGF-sequestration functions are coordinately regulated in vivo, the mechanism linking ADAMTS1 haploinsufficiency to NOS2 elevation in aortic disease, and whether ADAMTS1 has distinct or redundant roles relative to ADAMTS4/5 in specific tissue contexts.
  • No full-length ADAMTS1 structure
  • Catalytic versus non-catalytic functions not separable in vivo
  • ADAMTS1 versus ADAMTS4/5 redundancy not systematically tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0016787 hydrolase activity 3
Localization
GO:0005576 extracellular region 4 GO:0031012 extracellular matrix 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1474244 Extracellular matrix organization 6 R-HSA-162582 Signal Transduction 6 R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 3
Partners
ACANNID1NOTCH1SDC4TFPI2VCANVEGFAVEGFC

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 ADAMTS-1 protein is secreted and anchors to the extracellular matrix through its thrombospondin type I motifs and spacer region, with binding mediated through sulfated glycosaminoglycans such as heparan sulfate (displaced by heparin treatment). Deletion mutant analysis identified both the spacer region and three TSP type I motifs in the C-terminal region as necessary for tight ECM interaction. Transient expression in COS-7 cells, deletion mutant analysis, heparin displacement assay, cell fractionation The Journal of biological chemistry High 9593739
1999 METH-1 (human ADAMTS1) is a secreted, proteolytically processed protein that inhibits endothelial cell proliferation and suppresses FGF-2- and VEGF-induced angiogenesis in vivo, with no effect on fibroblast or smooth muscle cell growth, establishing endothelial-specific anti-angiogenic activity. Recombinant protein production, cornea pocket assay, chorioallantoic membrane assay, endothelial cell proliferation assay The Journal of biological chemistry High 10438512
2000 METH-1/ADAMTS1 is secreted as a pro-form that undergoes two consecutive proteolytic processing steps: furin cleaves the prodomain to release the p87 active form, and matrix metalloproteases (MMP-2, MMP-8, MMP-15) perform a second cleavage of p87 to release a p65 form that lacks two C-terminal thrombospondin repeats and shows reduced anti-angiogenic activity. Furin inhibitor treatment, purified furin incubation, MMP inhibitor treatment, recombinant MMP cleavage assay, heparin-binding analysis The Journal of biological chemistry High 10944521
2000 ADAMTS-1 is a transcriptional target of the progesterone receptor (PR) in granulosa cells of preovulatory follicles following the LH surge; PR knockout mice fail to induce ADAMTS-1 mRNA, and ADAMTS-1-null mice show growth retardation, impaired female fertility, renal calyceal enlargement with fibrosis, and abnormal adrenal medullary architecture, establishing essential roles in growth, organ morphology, and ovulation. PR knockout mouse model, gene targeting (ADAMTS-1 null mice), histology, Northern blot The Journal of clinical investigation High 10781075 10811842
2002 ADAMTS1 cleaves aggrecan at multiple sites including a previously identified site (E373-A) and additional new sites, classifying it as an aggrecanase. A point mutation in the zinc-binding domain abolishes catalytic activity. Latency is conferred by the prodomain (furin cleavage site mutant retains latency). Activity is inhibited by TIMP-2, TIMP-3, and a specific monoclonal antibody. In vitro protease assay on purified aggrecan, zinc-binding domain point mutagenesis, furin cleavage site mutagenesis, TIMP inhibition assay, peptide substrate activity assay Biochemical and biophysical research communications High 12054629
2003 Pro-ADAMTS-1 (110 kDa) is produced in mural granulosa cells and localized to cytoplasmic secretory vesicles; the mature 85-kDa form (prodomain-truncated) accumulates in the ECM of the cumulus-oocyte complex during matrix expansion. ADAMTS-1 cleaves versican in the COC matrix generating an N-terminal DPEAAE neoepitope fragment, and this cleavage is reduced in PRKO mouse ovaries deficient in ADAMTS-1. Immunofluorescence localization, Western blot of ovarian tissue, anti-neoepitope antibody detection of versican cleavage in PRKO vs. wild-type ovaries The Journal of biological chemistry High 12907688
2003 ADAMTS1 directly binds VEGF165 (but not VEGF121, which lacks the heparin-binding domain) via its carboxyl-terminal region, sequestering it and blocking VEGFR2 phosphorylation and endothelial cell proliferation. Inhibition is reversible; active VEGF can be recovered from the complex. ADAMTS1 and VEGF165 co-immunoprecipitate from tumor extracts. Co-immunoprecipitation, chemical cross-linking, domain deletion analysis, VEGFR2 phosphorylation assay, endothelial proliferation assay, tumor extract co-IP The Journal of biological chemistry High 12716911
2003 Adamts-1 null female mice are subfertile due to failure of mature oocytes to be released from ovarian follicles (ovulatory failure), while uterine function and embryo implantation are normal, establishing that ADAMTS-1 is specifically required for the tissue remodeling process of ovulation. Adamts-1 knockout mouse model, histology, fertility assay Biology of reproduction High 14668204
2004 Furin is the principal convertase cleaving proADAMTS-1 at Arg235 (RKKR235) in the Golgi apparatus prior to secretion. The prodomain also contains conserved cysteine residues (C106, C125, C181) and other residues (Y108, G110, 137-144 sequence) required for proper biosynthesis. PACE4 and PC6B can also process proADAMTS-1 but less efficiently than furin. Site-directed mutagenesis of furin recognition sequences and conserved prodomain residues, biosynthetic labeling in HEK293 cells, Brefeldin A/monensin Golgi disruption The Journal of biological chemistry High 15184385
2004 ADAMTS-1 gene transcription in granulosa cells is coordinately regulated by LH (via cAMP/PKA/Sp1/Sp3 and nuclear factor 1-like binding sites) and progesterone receptor (PRA/PRB acting as inducible coregulators via C/EBPβ and Sp1/Sp3 binding sites in the ADAMTS-1 promoter), despite absence of a consensus PR response element. Promoter-luciferase reporter assays with truncation and site-specific mutations, transfection of PRA/PRB expression vectors in granulosa cells, PR antagonist ZK98299 treatment Molecular endocrinology High 15256533
2006 ADAMTS-1 cleaves versican at multiple sites in cultured human aortic VSMCs and promotes VSMC migration, suggesting a role in atherogenesis through ECM remodeling. Transgenic overexpression in apoE-deficient mice increases intimal hyperplasia in the carotid artery flow cessation model. In vitro versican cleavage assay with peptide substrates, carotid artery flow cessation model in transgenic mice, VSMC migration assay Arteriosclerosis, thrombosis, and vascular biology Medium 15539621
2006 ADAMTS1 uses its proteolytic activity to promote pulmonary metastasis via shedding of transmembrane precursors of heparin-binding EGF (HB-EGF) and amphiregulin (AR), activating EGFR and ErbB-2. A catalytically dead mutant (ADAMTS-1E/Q) inhibits metastasis. Auto-proteolytic cleavage of ADAMTS1 generates N- and C-terminal fragments containing TSP motifs that inhibit metastasis and suppress ERK1/2 activation by HB-EGF/AR. Overexpression of full-length, catalytically dead mutant, and autocleavage fragments; in vivo pulmonary metastasis assays; EGFR/ErbB-2 phosphorylation assays; ERK1/2 activation assays Oncogene High 16314835
2006 ADAMTS1 interacts with and cleaves tissue factor pathway inhibitor-2 (TFPI-2), removing a protease-sensitive C-terminal region and altering TFPI-2's binding properties and extracellular localization, identified by yeast two-hybrid screen and confirmed by multiple biochemical assays. Yeast two-hybrid screen, co-immunoprecipitation, cell-based assays, in vitro cleavage assay The Journal of biological chemistry High 16641089
2006 ADAMTS1 is required for structural maintenance of ovarian follicular basement membranes during folliculogenesis and for ovarian lymphangiogenesis; ADAMTS-1-null ovaries show follicle dysmorphogenesis with ECM disruption and severely delayed lymphatic development beginning at antrum formation. ADAMTS-1 null mouse histology, immunostaining of basement membrane components and cell-type markers (Cyp-17, AMH), lymphatic vessel immunostaining Developmental biology High 17097630
2006 Proteomic (DIGE) screening identified nidogen-1, nidogen-2, desmocollin-3, dystroglycan 1, and Mac-2-binding protein as putative ADAMTS1 substrates; nidogen-1 and nidogen-2 were validated as substrates by immunochemical analysis. DIGE proteomics of conditioned medium from ADAMTS1-overexpressing cells, mass spectrometry, immunochemical validation Proteomics Medium 16511810
2007 Crystal structures of human ADAMTS-1 reveal a conserved zinc metalloprotease catalytic domain with a larger S1' selectivity pocket than ADAM33 and an unexpected double calcium-binding site. The 'disintegrin-like' domain is structurally homologous to cysteine-rich domains of other metalloproteinases (not classical disintegrin domains), and it stacks against the active site suggesting a possible regulatory role. Structures obtained in apo form and in complex with inhibitor marimastat. X-ray crystallography (crystal structures of catalytic and disintegrin-like domains, with and without marimastat) Journal of molecular biology High 17897672
2008 Endocardial Brg1 (chromatin remodeling protein) represses ADAMTS1 expression in the endocardium overlying developing trabeculae; repression of ADAMTS1 allows establishment of an ECM environment (cardiac jelly) that supports trabecular growth. Loss of Brg1 leads to ADAMTS1 upregulation, cardiac jelly degradation, and impaired trabeculation. Conditional Brg1 knockout mouse (endocardium-specific), genetic epistasis between Brg1 and ADAMTS1, rescue by ADAMTS1 deletion, histology and molecular analysis Developmental cell High 18267097
2008 ADAMTS1 cleaves the ectodomain of syndecan-4, a membrane-bound heparan sulfate proteoglycan, resulting in altered cytoskeletal organization, loss of focal adhesions, and increased cell migration. ADAMTS1 proteolytic action on syndecan-4 mimics the phenotype of genetic syndecan-4 deletion. In vitro cleavage assay, cytoskeleton immunostaining, focal adhesion analysis, migration assay in syndecan-4 null cells The international journal of biochemistry & cell biology High 18775505
2009 ADAMTS1 and MMP1 orchestrate a paracrine signaling cascade in bone metastasis: ADAMTS1 proteolytically releases membrane-bound EGF-like ligands (amphiregulin, HB-EGF, TGFα) from tumor cells, which suppress osteoprotegerin (OPG) in osteoblasts and potentiate osteoclast differentiation, promoting osteolytic bone metastasis. In vitro shedding assays, EGFR signaling assays in osteoblasts, osteoclastogenesis assays, EGFR inhibitor treatment, bone metastasis mouse model Genes & development High 19608765
2009 ADAMTS1 cleaves semaphorin 3C, releasing it from the extracellular matrix, and this cleavage promotes migration of breast cancer cells. Identified by two independent proteomic approaches (DIGE and SILAC). DIGE proteomics, SILAC, substrate validation assays, cell migration assay The Journal of biological chemistry High 19915008
2009 ADAMTS1 is a hypoxia-inducible gene specifically in endothelial cells (not other cell types); HIF-1 binds to HIF binding sites in the ADAMTS1 promoter under hypoxia (confirmed by ChIP). Hypoxia-induced expression is mediated via the PI3K pathway. Recombinant ADAMTS1 promotes endothelial cell migration under hypoxic conditions. RT-PCR and Western blot in multiple cell types, CoCl2 hypoxia mimetic, PI3K inhibitor (LY294002), secreted luciferase reporter assay, chromatin immunoprecipitation (ChIP) for HIF-1, endothelial migration assay The Journal of biological chemistry High 19349275
2012 Pericyte-derived TIMP3 stabilizes and ADAMTS1 destabilizes capillary tubular networks in 3D gel assays. Kidney pericytes rapidly activate ADAMTS1 and downregulate TIMP3 after injury, promoting detachment and differentiation into myofibroblasts. TIMP3-null mice show spontaneous microvascular phenotype and exaggerated injury response. 3D capillary tube formation/stabilization assay with pericytes, TIMP3-null mouse kidney phenotyping, gene expression analysis Journal of the American Society of Nephrology High 22383695
2013 ADAMTS1 acts as a tumor suppressor in breast carcinoma by cleaving nidogen-1 and nidogen-2 from vascular basement membranes, causing vessel morphological alterations and decreased vessel density. Increased ADAMTS1 expression leads to complete inhibition of tumor xenograft growth. Tumor xenograft model, immunofluorescence of vascular structures, nidogen cleavage assay, tumor vessel density analysis International journal of cancer Medium 23681936
2016 SPARC treatment of cardiac fibroblasts increases secretion of both collagen I and ADAMTS1 (both 110-kDa latent and 87-kDa active forms) and activates TGF-β1-Smad2 signaling. An ADAMTS1-blocking antibody suppresses SPARC-induced collagen I secretion, establishing that SPARC promotes cardiac collagen deposition through ADAMTS1. Cardiac fibroblast stimulation with recombinant SPARC, ADAMTS1-blocking antibody, Western blot of conditioned media, picrosirius red collagen staining in aged WT and SPARC-null mice American journal of physiology. Endocrinology and metabolism Medium 27143554
2017 Macrophage-released ADAMTS1 promotes satellite cell (muscle stem cell) activation after muscle injury by targeting NOTCH1 as a metalloproteinase substrate, reducing Notch signaling and thereby increasing satellite cell activation. Overexpression of ADAMTS1 in macrophages in vivo is sufficient to increase satellite cell activation and improve muscle regeneration. In vivo macrophage-specific ADAMTS1 overexpression, satellite cell activation quantification, Notch signaling assays, identification of Notch1 as ADAMTS1 substrate Nature communications High 28939843
2017 Genetic haploinsufficiency of Adamts1 in mice causes thoracic aortic aneurysms and dissections (TAAD) similar to Marfan syndrome, mediated by elevated NOS2 and nitric oxide levels. Pharmacological or genetic inhibition of NOS2 protects Adamts1-haploinsufficient mice and MFS mice from aortic pathology and rapidly reverses aortic dilation. Adamts1 haploinsufficient and Nos2 knockout mouse models, aortic pathology quantification, pharmacological NOS2 inhibition, measurement of nitric oxide/NOS2 levels Nature medicine High 28067899
2016 Adamts1 (targeted by miR-181d) impairs adipocyte lineage commitment through its metalloprotease activity by remodeling ECM components and activating FAK-ERK signaling. Adipose tissue-specific ablation of Adamts1 increases adipose mass, reduces insulin sensitivity, and disrupts lipid homeostasis. Forced expression and siRNA knockdown of Adamts1, catalytically inactive mutant, adipogenesis assay, FAK-ERK signaling measurements, adipose-specific conditional KO mouse Cell death and differentiation High 27447109
2020 ADAMTS1 and syndecan-4 functionally interact in regulating endothelial cell adhesion, migration, and angiogenesis. ADAMTS1 knockdown reduces cell surface syndecan-4 via increased MMP9 activity. Both knockdowns enhance VEGFA164 responses and aortic ring sprouting. The altered adhesive phenotype is matrix-dependent and correlates with loss of fibulin-1 (an extracellular co-factor for ADAMTS1 known to inhibit migration) from the conditioned matrix. siRNA knockdown of ADAMTS1 and syndecan-4, MMP9 activity assay, VEGF signaling assays, aortic ring sprouting assay, cell migration assay on fibronectin, cell-conditioned matrix plating experiments Journal of cell science Medium 32269093
2021 Label-free quantitative proteomics identified 21 novel ADAMTS1 cleavage sites in versican V1 beyond the canonical Glu441-Ala442 site, using LC-MS/MS of digests with active versus catalytically inactive ADAMTS1. ADAMTS1/4/5 share a preference for P1-Glu residues in proteoglycan substrates. In vitro recombinant versican digestion with active and catalytically inactive ADAMTS1, label-free LC-MS/MS, z-score statistical approach for cleavage site ranking Journal of proteomics High 34450332
2014 ADAMTS1 inhibits lymphangiogenesis by binding VEGFC and attenuating VEGFR3 phosphorylation in lymphatic endothelial cells (HMVEC-dLy), reducing proliferation and tube formation. ADAMTS1-VEGFC complex formation confirmed by immunoprecipitation. Adenoviral ADAMTS1 gene transduction in HMVEC-dLy, proliferation and tube formation assays, VEGFR3 phosphorylation assay, immunoprecipitation of ADAMTS1-VEGFC complex Experimental cell research Medium 24631293

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases. Proceedings of the National Academy of Sciences of the United States of America 440 10781075
1999 METH-1, a human ortholog of ADAMTS-1, and METH-2 are members of a new family of proteins with angio-inhibitory activity. The Journal of biological chemistry 351 10438512
2000 ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function. The Journal of clinical investigation 272 10811842
2009 ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis. Genes & development 247 19608765
1979 The alternative pathway C3/C5 convertase: chemical basis of factor B activation. Journal of immunology (Baltimore, Md. : 1950) 231 458145
2003 Processing and localization of ADAMTS-1 and proteolytic cleavage of versican during cumulus matrix expansion and ovulation. The Journal of biological chemistry 222 12907688
2008 Endocardial Brg1 represses ADAMTS1 to maintain the microenvironment for myocardial morphogenesis. Developmental cell 207 18267097
2003 ADAMTS1/METH1 inhibits endothelial cell proliferation by direct binding and sequestration of VEGF165. The Journal of biological chemistry 203 12716911
1998 ADAMTS-1 protein anchors at the extracellular matrix through the thrombospondin type I motifs and its spacing region. The Journal of biological chemistry 194 9593739
2002 ADAMTS1 cleaves aggrecan at multiple sites and is differentially inhibited by metalloproteinase inhibitors. Biochemical and biophysical research communications 192 12054629
2012 Pericyte TIMP3 and ADAMTS1 modulate vascular stability after kidney injury. Journal of the American Society of Nephrology : JASN 168 22383695
2003 Adamts-1 is essential for the development and function of the urogenital system. Biology of reproduction 150 14668204
2004 Role of ADAMTS-1 in atherosclerosis: remodeling of carotid artery, immunohistochemistry, and proteolysis of versican. Arteriosclerosis, thrombosis, and vascular biology 149 15539621
2017 Nitric oxide mediates aortic disease in mice deficient in the metalloprotease Adamts1 and in a mouse model of Marfan syndrome. Nature medicine 148 28067899
2008 Renal ischemia reperfusion inhibits VEGF expression and induces ADAMTS-1, a novel VEGF inhibitor. American journal of physiology. Renal physiology 143 18272597
2000 Characterization of METH-1/ADAMTS1 processing reveals two distinct active forms. The Journal of biological chemistry 133 10944521
2006 Full-length ADAMTS-1 and the ADAMTS-1 fragments display pro- and antimetastatic activity, respectively. Oncogene 131 16314835
2012 Role of C3, C5 and anaphylatoxin receptors in acute lung injury and in sepsis. Advances in experimental medicine and biology 129 21948367
2019 Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood. Clinical epigenetics 124 30953539
2006 ADAMTS1, CRABP1, and NR3C1 identified as epigenetically deregulated genes in colorectal tumorigenesis. Cellular oncology : the official journal of the International Society for Cellular Oncology 123 17167179
2007 Differential contributions of C3, C5, and decay-accelerating factor to ethanol-induced fatty liver in mice. Gastroenterology 120 17383432
2017 Macrophage-released ADAMTS1 promotes muscle stem cell activation. Nature communications 109 28939843
2004 Coordinate transcription of the ADAMTS-1 gene by luteinizing hormone and progesterone receptor. Molecular endocrinology (Baltimore, Md.) 106 15256533
2006 Requirement for ADAMTS-1 in extracellular matrix remodeling during ovarian folliculogenesis and lymphangiogenesis. Developmental biology 105 17097630
2009 The cleavage of semaphorin 3C induced by ADAMTS1 promotes cell migration. The Journal of biological chemistry 87 19915008
2003 ADAMTS1: a matrix metalloprotease with angioinhibitory properties. Annals of the New York Academy of Sciences 87 12814950
2001 Expression of METH-1 and METH-2 in pancreatic cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 84 11705860
1987 Long C3-C5 propriospinal neurones in the cat. Brain research 82 3032341
2012 ADAMTS-1 and ADAMTS-4 levels are elevated in thoracic aortic aneurysms and dissections. The Annals of thoracic surgery 72 23245439
2008 Cleavage of syndecan-4 by ADAMTS1 provokes defects in adhesion. The international journal of biochemistry & cell biology 67 18775505
2013 The metalloproteinase ADAMTS1: a comprehensive review of its role in tumorigenic and metastatic pathways. International journal of cancer 66 23444028
2007 Crystal structures of human ADAMTS-1 reveal a conserved catalytic domain and a disintegrin-like domain with a fold homologous to cysteine-rich domains. Journal of molecular biology 64 17897672
2011 The ADAMTS1 protease gene is required for mammary tumor growth and metastasis. The American journal of pathology 63 22001177
2010 Increased expression of HIF-1alpha, VEGF-A and its receptors, MMP-2, TIMP-1, and ADAMTS-1 at the venous stenosis of arteriovenous fistula in a mouse model with renal insufficiency. Journal of vascular and interventional radiology : JVIR 63 20598569
1980 The interaction of C5 with C3b in free solution: a sufficient condition for cleavage by a fluid phase C3/C5 convertase. Journal of immunology (Baltimore, Md. : 1950) 63 7350230
2012 Breast cancer cells induce stromal fibroblasts to secrete ADAMTS1 for cancer invasion through an epigenetic change. PloS one 62 22514714
2009 ADAMTS1 is a unique hypoxic early response gene expressed by endothelial cells. The Journal of biological chemistry 62 19349275
2005 ADAMTS1 proteinase is up-regulated in wounded skin and regulates migration of fibroblasts and endothelial cells. The Journal of biological chemistry 62 15843381
1997 The exon/intron organization and chromosomal mapping of the mouse ADAMTS-1 gene encoding an ADAM family protein with TSP motifs. Genomics 62 9441751
2009 Differential effects of ADAMTS-1, -4, and -5 in the trabecular meshwork. Investigative ophthalmology & visual science 60 19553617
2002 Expression of ADAMTS1 during murine development. Mechanisms of development 59 12049787
2008 ADAMTS-1 metalloproteinase promotes tumor development through the induction of a stromal reaction in vivo. Cancer research 57 19010931
2006 ADAMTS-1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes. Brain research 57 16630594
2006 Identification of substrates of the extracellular protease ADAMTS1 by DIGE proteomic analysis. Proteomics 52 16511810
2006 ADAMTS1 interacts with, cleaves, and modifies the extracellular location of the matrix inhibitor tissue factor pathway inhibitor-2. The Journal of biological chemistry 51 16641089
2013 Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion. Molecular cancer 50 23289900
2005 Expression of versican and ADAMTS1, 4, and 5 during bone development in the rat mandible and hind limb. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 50 15983115
2006 Activation of complement C3, C5, and C9 genes in tumors treated by photodynamic therapy. Cancer immunology, immunotherapy : CII 49 16947020
2000 ADAMTS-1: A cellular disintegrin and metalloprotease with thrombospondin motifs is a target for parathyroid hormone in bone. Endocrinology 49 11108265
2016 Increased ADAMTS1 mediates SPARC-dependent collagen deposition in the aging myocardium. American journal of physiology. Endocrinology and metabolism 48 27143554
2010 RETRACTED: Variable inhibition of thrombospondin 1 against liver and lung metastases through differential activation of metalloproteinase ADAMTS1. Cancer research 48 20103648
2020 Bacterial synthesis of C3-C5 diols via extending amino acid catabolism. Proceedings of the National Academy of Sciences of the United States of America 46 32719126
2004 Dynamic induction of ADAMTS1 gene in the early phase of acute myocardial infarction. Journal of biochemistry 45 15625312
2010 ADAMTS-1: a new human ovulatory gene and a cumulus marker for fertilization capacity. Molecular and cellular endocrinology 43 20655981
2006 Vascular endothelial growth factor upregulates expression of ADAMTS1 in endothelial cells through protein kinase C signaling. Investigative ophthalmology & visual science 43 16936124
2003 Regulation of transcripts encoding ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin-like motifs-1) and progesterone receptor by human chorionic gonadotropin in equine preovulatory follicles. Journal of molecular endocrinology 43 14664708
2021 Pan-Cancer Analysis of Immune Complement Signature C3/C5/C3AR1/C5AR1 in Association with Tumor Immune Evasion and Therapy Resistance. Cancers 39 34439277
2020 ADAMTS-1 and syndecan-4 intersect in the regulation of cell migration and angiogenesis. Journal of cell science 39 32269093
2008 Association between ADAMTS1 matrix metalloproteinase gene variation, coronary heart disease, and benefit of statin therapy. Arteriosclerosis, thrombosis, and vascular biology 39 18174457
2006 Differential effects of interleukin-1beta and transforming growth factor-beta1 on the expression of the inflammation-associated protein, ADAMTS-1, in human decidual stromal cells in vitro. Human reproduction (Oxford, England) 39 16675485
2017 MiR-362-3p inhibits the proliferation and migration of vascular smooth muscle cells in atherosclerosis by targeting ADAMTS1. Biochemical and biophysical research communications 38 28890348
2014 Evidence for decreased expression of ADAMTS-1 associated with impaired oocyte quality in PCOS patients. The Journal of clinical endocrinology and metabolism 38 24646063
2005 Metalloproteinase ADAMTS-1 but not ADAMTS-5 is manifold overexpressed in neurodegenerative disorders as Down syndrome, Alzheimer's and Pick's disease. Brain research. Molecular brain research 38 15661359
1991 Human umbilical vein endothelial cells synthesize functional C3, C5, C6, C8 and C9 in vitro. Scandinavian journal of immunology 38 2047760
2013 ADAMTS1, ADAMTS5, ADAMTS9 and aggrecanase-generated proteoglycan fragments are induced following spinal cord injury in mouse. Neuroscience letters 37 23562508
2013 Contribution of ADAMTS1 as a tumor suppressor gene in human breast carcinoma. Linking its tumor inhibitory properties to its proteolytic activity on nidogen-1 and nidogen-2. International journal of cancer 37 23681936
2021 Identification of novel ADAMTS1, ADAMTS4 and ADAMTS5 cleavage sites in versican using a label-free quantitative proteomics approach. Journal of proteomics 36 34450332
2015 The ADAMTS1 Gene Is Associated with Familial Mandibular Prognathism. Journal of dental research 36 26124221
2012 Tumor growth inhibitory effect of ADAMTS1 is accompanied by the inhibition of tumor angiogenesis. Cancer science 36 22776012
2004 Identification of prodomain determinants involved in ADAMTS-1 biosynthesis. The Journal of biological chemistry 36 15184385
2016 Clinical significance of ADAMTS1, ADAMTS5, ADAMTS9 aggrecanases and IL-17A, IL-23, IL-33 cytokines in polycystic ovary syndrome. Journal of endocrinological investigation 35 27146815
2004 ADAMTS-1, a gene product of articular chondrocytes in vivo and in vitro, is downregulated by interleukin 1beta. The Journal of rheumatology 34 14760803
1990 Synthesis of C3, C5, C6, C7, C8, and C9 by human fibroblasts. Scandinavian journal of immunology 34 2270435
2010 PGF2α-F-prostanoid receptor signalling via ADAMTS1 modulates epithelial cell invasion and endothelial cell function in endometrial cancer. BMC cancer 33 20840749
2016 The miR-181d-regulated metalloproteinase Adamts1 enzymatically impairs adipogenesis via ECM remodeling. Cell death and differentiation 32 27447109
2020 Melatonin-triggered post-transcriptional and post-translational modifications of ADAMTS1 coordinately retard tumorigenesis and metastasis of renal cell carcinoma. Journal of pineal research 31 32408377
2015 miR‑365 overexpression promotes cell proliferation and invasion by targeting ADAMTS-1 in breast cancer. International journal of oncology 31 25998153
1988 Complement activation in patients with renal failure as detected through the quantitation of fragments of the complement proteins C3, C5, and factor B. Klinische Wochenschrift 31 3184764
2008 HDAC inhibition upregulates the expression of angiostatic ADAMTS1. FEBS letters 30 19007777
2001 A disintegrin and metalloprotease with thrombospondin type1 motifs (ADAMTS-1) and IL-1 receptor type 1 mRNAs are simultaneously induced in nerve injured motor neurons. Brain research. Molecular brain research 30 11311987
2005 Abundance of ADAM-8, -9, -10, -12, -15 and -17 and ADAMTS-1 in mouse uterus during the oestrous cycle. Reproduction, fertility, and development 29 15907280
2004 Neonatal calyceal dilation and renal fibrosis resulting from loss of Adamts-1 in mouse kidney is due to a developmental dysgenesis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 29 15615810
1989 A human immunoglobulin IGHG3 allele (Gmb0,b1,c3,c5,u) with an IGHG4 converted region and three hinge exons. Immunogenetics 29 2571587
2008 Aberrant methylation of ADAMTS1 in non-small cell lung cancer. Cancer genetics and cytogenetics 28 19027488
2006 Expression of ADAMTS-1, -4, -5 and TIMP-3 in normal and multiple sclerosis CNS white matter. Multiple sclerosis (Houndmills, Basingstoke, England) 28 16900752
2005 The hyalectan degrading ADAMTS-1 enzyme is expressed by osteoblasts and up-regulated at regions of new bone formation. Bone 27 15777654
2015 A disintegrin and metalloproteinase with thrombospondin motif 1 (ADAMTS1) expression increases in acute aortic dissection. Science China. Life sciences 26 26563155
2015 Adamts1 mediates ethanol-induced alterations in collagen and elastin via a FoxO1-sestrin3-AMPK signaling cascade in myocytes. Journal of cellular biochemistry 25 25142777
2002 A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-1 null mutant mice develop renal lesions mimicking obstructive nephropathy. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 25 12386284
2004 High-density lipoprotein subfraction 3 decreases ADAMTS-1 expression induced by lipopolysaccharide and tumor necrosis factor-alpha in human endothelial cells. Matrix biology : journal of the International Society for Matrix Biology 24 14996435
2012 Expression of ADAMTS1 and its correlation with angiogenesis in primary gastric cancer and lymph node metastasis. Digestive diseases and sciences 23 23001403
2010 ADAMTS1 alters blood vessel morphology and TSP1 levels in LNCaP and LNCaP-19 prostate tumors. BMC cancer 23 20546609
2019 A disintegrin-like and metalloproteinase with thrombospondin-1 (ADAMTS-1) levels in gingival crevicular fluid correlate with vascular endothelial growth factor-A, hypoxia-inducible factor-1α, and clinical parameters in patients with advanced periodontitis. Journal of periodontology 22 31020669
2019 ADAMTS-1 inhibits angiogenesis via the PI3K/Akt-eNOS-VEGF pathway in lung cancer cells. Translational cancer research 22 35117030
2014 ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor. Experimental cell research 22 24631293
2005 Differential expression of ADAMTS-1, -4, -5 and TIMP-3 in rat spinal cord at different stages of acute experimental autoimmune encephalomyelitis. Journal of autoimmunity 22 16303287
2018 ADAMTS1 protease is required for a balanced immune cell repertoire and tumour inflammatory response. Scientific reports 21 30166561
2018 Abnormal expressions of ADAMTS-1, ADAMTS-9 and progesterone receptors are associated with lower oocyte maturation in women with polycystic ovary syndrome. Archives of gynecology and obstetrics 21 30446843
2013 Expression of ADAMTS1 mRNA in bovine endometrium and placenta during gestation. Domestic animal endocrinology 21 23751571
2013 Molecular characterization and transcriptional regulation of a disintegrin and metalloproteinase with thrombospondin motif 1 (ADAMTS1) in bovine preovulatory follicles. Endocrinology 21 23751874