Affinage

ADAMTS1

A disintegrin and metalloproteinase with thrombospondin motifs 1 · UniProt Q9UHI8

Length
967 aa
Mass
105.4 kDa
Annotated
2026-06-09
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADAMTS1 (METH-1) is a secreted, extracellular-matrix-associated zinc metalloprotease that remodels the pericellular matrix and modulates angiogenic and morphogenetic signaling, establishing it as an anti-angiogenic and matrix-remodeling factor (PMID:10438512, PMID:10373500). It is produced as a latent proenzyme that is activated by furin-mediated prodomain removal in the secretory pathway, then further processed by MMP-2/8/15 at its C-terminus to generate a p65 form that loses two thrombospondin repeats, reduced heparin affinity, and reduced anti-proliferative activity (PMID:10373500, PMID:10944521); catalysis depends on an intact zinc-binding motif and is restrained by TIMP-2 and TIMP-3 (PMID:12054629). Through its proteolytic activity ADAMTS1 cleaves an extensive set of matrix and cell-surface substrates including aggrecan, versican (generating the DPEAAE neoepitope), nidogen-1/2, syndecan-4, semaphorin 3C, TFPI-2, and NOTCH1, and sheds membrane-bound EGF-family ligands (HB-EGF, amphiregulin, TGFα) (PMID:12054629, PMID:12907688, PMID:16511810, PMID:18775505, PMID:19915008, PMID:28939843, PMID:16314835, PMID:34450332); fibulin-1 acts as a cofactor that enhances aggrecan cleavage (PMID:16061471). Independent of catalysis, ADAMTS1 sequesters the heparin-binding forms of VEGF165 and VEGF-C via its C-terminal thrombospondin repeats to suppress VEGFR2 and VEGFR3 phosphorylation and endothelial/lymphatic proliferation (PMID:12716911, PMID:24631293). Its expression is tightly controlled: induced by LH/cAMP/PKA and progesterone receptor in ovulating granulosa cells (PMID:15256533), by hypoxia through HIF-1 in endothelial cells (PMID:19349275), and downstream of VEGF–VEGFR2–PLCγ–PKCβ signaling (PMID:16936124), and repressed by HDAC6/SP1 (PMID:19007777). These activities translate into context-dependent physiological roles in ovulation through versican cleavage (PMID:12907688), cardiac trabeculation through cardiac jelly degradation (PMID:18267097), muscle stem cell activation through NOTCH1 cleavage (PMID:28939843), adipocyte commitment via FAK-ERK signaling (PMID:27447109), vascular homeostasis through an ADAMTS1–NOS2 axis whose disruption causes thoracic aortic aneurysm (PMID:28067899), and both pro- and anti-tumorigenic effects in breast, bone, and pulmonary metastasis (PMID:16314835, PMID:19608765, PMID:22001177, PMID:23681936).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1999 High

    Establishing that the protein is a genuine secreted enzyme and an anti-angiogenic factor defined the foundational identity of ADAMTS1.

    Evidence Recombinant protein in endothelial proliferation, cornea pocket, and CAM assays; alpha2-macroglobulin trapping, zinc-motif mutagenesis, and furin-deficient cell complementation

    PMID:10373500 PMID:10438512

    Open questions at the time
    • In vivo physiological substrate(s) not yet identified
    • Mechanism of anti-angiogenesis (proteolytic vs. binding) not resolved at this stage
  2. 2000 High

    Defining sequential furin then MMP processing showed activation and maturation generate functionally distinct forms, explaining how proteolytic state tunes activity.

    Evidence Furin/MMP inhibitors and purified enzymes, heparin affinity chromatography, endothelial proliferation readout

    PMID:10944521

    Open questions at the time
    • Physiological trigger for C-terminal processing in vivo unclear
    • Functional role of the released C-terminal TSR fragments not defined here
  3. 2002 High

    Identifying ADAMTS1 as an aggrecanase with defined inhibitor sensitivity placed it in matrix proteoglycan turnover.

    Evidence In vitro ECM protease assays, zinc-motif and furin-site mutants, TIMP-2/3 and monoclonal antibody inhibition

    PMID:12054629

    Open questions at the time
    • Physiological relevance of aggrecan cleavage in tissue not established
    • Substrate repertoire beyond aggrecan not yet mapped
  4. 2003 High

    Discovery of direct VEGF165 sequestration via the C-terminal region revealed a catalysis-independent mechanism for anti-angiogenesis.

    Evidence Co-IP, cross-linking, domain deletion, VEGFR2 phosphorylation assay, tumor extract validation

    PMID:12716911

    Open questions at the time
    • Relative contribution of sequestration vs. proteolysis to angiogenesis in vivo unclear
    • Reversibility implications for tissue VEGF bioavailability untested
  5. 2003 High

    Demonstrating ovary-specific versican cleavage and subcellular trafficking linked ADAMTS1 proteolysis to a defined physiological process, ovulation.

    Evidence Domain-specific antibodies, immunofluorescence, versican neoepitope detection, PRKO mouse

    PMID:12907688

    Open questions at the time
    • Whether versican cleavage alone is sufficient for COC expansion not established
  6. 2004 High

    Mapping the LH/cAMP/PKA and PR-coregulated promoter explained how ADAMTS1 is transcriptionally induced during ovulation.

    Evidence Promoter-luciferase truncation/mutant constructs, PR antagonist, PRA/PRB co-transfection, cAMP analogs in granulosa cells

    PMID:15256533

    Open questions at the time
    • How PR acts without a consensus PRE not mechanistically resolved
    • Generality of this regulation outside granulosa cells unknown
  7. 2005 High

    Identifying fibulin-1 as a binding cofactor that enhances aggrecan cleavage showed ADAMTS1 activity is modulated by ECM partners.

    Evidence Yeast two-hybrid, affinity chromatography, co-IP, pulldown, ELISA, in vitro aggrecan cleavage

    PMID:16061471

    Open questions at the time
    • Structural basis of fibulin-1-mediated enhancement unknown
    • Whether fibulin-1 modulates other substrates not tested
  8. 2005 High

    Demonstrating concentration-dependent dual control of cell migration (proteolytic stimulation vs. FGF-2 sequestration) revealed ADAMTS1 as a context-dependent migration regulator in wound healing.

    Evidence Wound-tissue immunofluorescence, KO mouse skin, migration assays with recombinant/protease-dead protein, FGF-2 binding

    PMID:15843381

    Open questions at the time
    • Local concentration thresholds in tissue not defined
    • FGF-2 sequestration domain not precisely mapped
  9. 2006 High

    Expanding the substrate set (TFPI-2, nidogen-1/2 and other proteomics hits) and defining VEGF-driven induction broadened both the enzymatic repertoire and upstream regulation of ADAMTS1.

    Evidence Yeast two-hybrid plus biochemical cleavage; DIGE/MS with immunochemical validation; VEGF stimulation with VEGFR2/PLCγ/PKC inhibitors and siRNA

    PMID:16511810 PMID:16641089 PMID:16936124

    Open questions at the time
    • Physiological significance of TFPI-2 and nidogen cleavage in tissue not established
    • Several DIGE-identified substrates remain unvalidated
  10. 2008 High

    Identifying syndecan-4 cleavage, HDAC6/SP1 repression, and Brg1-controlled cardiac repression connected ADAMTS1 to cytoskeletal/adhesion control, epigenetic regulation, and heart morphogenesis.

    Evidence Recombinant cleavage with syndecan-4 null cells and focal adhesion/migration assays; promoter-luciferase, ChIP, DAPA with HDAC inhibitors; Brg1 conditional endocardial KO with cardiac phenotyping

    PMID:18267097 PMID:18775505 PMID:19007777

    Open questions at the time
    • How a single protease coordinates these distinct outputs in vivo unclear
    • HDAC6/SP1 repression evidence from a single lab
  11. 2009 High

    Linking ADAMTS1 to EGF-ligand shedding, semaphorin 3C cleavage, paracrine bone metastasis, and HIF-1 hypoxic induction defined its proteolytic role in tumor signaling and stress-responsive expression.

    Evidence WT vs. protease-dead overexpression and metastasis models; DIGE/SILAC proteomics with migration assays; conditioned-medium transfer to osteoblasts with EGFR inhibitors; hypoxia/ChIP with HIF-1 binding sites

    PMID:16314835 PMID:19349275 PMID:19608765 PMID:19915008

    Open questions at the time
    • Reconciling pro- vs. anti-tumor roles across contexts not resolved
    • Semaphorin 3C cleavage from a single lab
  12. 2011 High

    Genetic loss in a mammary tumor model showed ADAMTS1 is required for tumor growth and metastasis and shapes the immune/versican tumor microenvironment.

    Evidence Adamts1 KO crossed with MMTV-PyMT, histology, apoptosis, versican neoepitope, CD45/IL-12 immune phenotyping

    PMID:22001177

    Open questions at the time
    • Whether immune effects are downstream of versican cleavage not directly tested
  13. 2012 High

    Implicating ADAMTS1 in pericyte-driven microvascular destabilization opposed by TIMP3 extended its vascular role to injury-induced rarefaction.

    Evidence In vivo pericyte expression profiling, 3D capillary tube assay, Timp3 KO mouse

    PMID:22383695

    Open questions at the time
    • Substrate mediating destabilization not identified
  14. 2014 Medium

    Showing VEGF-C sequestration that suppresses VEGFR3 generalized the C-terminal ligand-trapping mechanism to lymphangiogenesis.

    Evidence Adenoviral ADAMTS1 in lymphatic endothelial cells, proliferation/tube/migration assays, VEGFR3 phosphorylation, co-IP

    PMID:24631293

    Open questions at the time
    • Single Co-IP; in vivo relevance to lymphatic biology untested
  15. 2013 Medium

    Defining nidogen cleavage that disrupts vascular basement membranes assigned ADAMTS1 a tumor-suppressive anti-angiogenic mechanism in breast xenografts.

    Evidence Xenograft with ADAMTS1 overexpression, nidogen and vessel immunostaining, microvessel density

    PMID:23681936

    Open questions at the time
    • Single lab; contrasts with pro-metastatic roles in other models
  16. 2016 High

    Distinguishing protease-dependent control of adipocyte commitment and SPARC-driven cardiac collagen deposition refined ADAMTS1's roles in lineage commitment and cardiac matrix remodeling.

    Evidence Catalytic mutant, adipose-specific KO, FAK-ERK readouts, miR-181d targeting; SPARC-null mice, fibroblast stimulation, blocking antibody, versican immunostaining

    PMID:27143554 PMID:27447109

    Open questions at the time
    • Direct ECM substrate driving adipocyte FAK-ERK signaling not pinpointed
    • SPARC-ADAMTS1 collagen link from a single lab
  17. 2017 High

    Identifying NOTCH1 as a direct substrate for muscle stem cell activation and placing ADAMTS1 upstream of the NOS2 vascular axis (aortic aneurysm) demonstrated specific in vivo signaling and disease mechanisms.

    Evidence Macrophage-specific Adamts1 overexpression with NOTCH1 cleavage/satellite cell assays; Adamts1 haploinsufficient mice with Nos2 KO and pharmacological NOS2 inhibition

    PMID:28067899 PMID:28939843

    Open questions at the time
    • How NOS2 is regulated downstream of ADAMTS1 not molecularly defined
    • Substrate connecting ADAMTS1 loss to NOS2 elevation unidentified
  18. 2020 Medium

    Connecting ADAMTS1, syndecan-4, MMP9, and fibulin-1 in endothelial adhesion and VEGFA responses integrated several earlier partners into one angiogenic regulatory network.

    Evidence siRNA knockdowns, MMP9 activity, VEGFA response, aortic ring sprouting, conditioned matrix and fibulin-1 analysis

    PMID:32269093

    Open questions at the time
    • Causality among the network nodes incompletely resolved
    • Single lab
  19. 2021 High

    High-resolution mapping of versican V1 cleavage sites with a catalytically inactive control provided definitive enzymatic characterization of a principal substrate.

    Evidence In vitro digestion of recombinant versican V1, active vs. inactive ADAMTS1, label-free LC-MS/MS

    PMID:34450332

    Open questions at the time
    • Biological role of the 21 novel cleavage sites in tissue not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ADAMTS1's many context-dependent roles (pro- vs. anti-angiogenic, pro- vs. anti-tumor) are selected by tissue, processing state, cofactor availability, and substrate context remains the central unresolved question.
  • No unifying framework reconciling opposing phenotypes
  • Relative in vivo contributions of catalytic vs. ligand-sequestering activities unquantified
  • Structural basis of substrate and cofactor selectivity unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016787 hydrolase activity 3 GO:0140313 molecular sequestering activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1474244 Extracellular matrix organization 5 R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 2
Partners
A2MFBLN1SDC4TIMP2TIMP3VEGFAVEGFC

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 ADAMTS1/METH-1 is a secreted, proteolytically processed protein with metalloprotease, disintegrin-like, and thrombospondin-type-1 repeat domains that inhibits endothelial cell proliferation and suppresses FGF-2- and VEGF-induced angiogenesis in vivo (cornea pocket and CAM assays), establishing it as an anti-angiogenic factor. Recombinant protein production, endothelial cell proliferation assay, cornea pocket assay, chorioallantoic membrane assay The Journal of biological chemistry High 10438512
1999 ADAMTS1 is an active metalloprotease: it forms a covalent complex with alpha2-macroglobulin (proteinase trapping), and a point mutation in the zinc-binding motif abolishes this activity. The prodomain is removed by furin endopeptidase in the secretory pathway, as shown by impaired processing in furin-deficient LoVo cells restored by furin co-expression. The mature protein associates with the extracellular matrix. alpha2-macroglobulin trapping assay, zinc-binding domain point mutagenesis, furin-deficient cell line complementation, co-expression rescue The Journal of biological chemistry High 10373500
2000 Secreted pro-ADAMTS1 (METH-1) is processed in two consecutive steps: (1) furin cleaves the prodomain to release an 87 kDa active form (p87); (2) MMP-2, MMP-8, or MMP-15 further cleave p87 at the C-terminal end to release a 65 kDa form (p65) lacking two thrombospondin repeats. The p65 form shows reduced affinity for heparin and reduced suppression of endothelial cell proliferation compared to p87. Furin inhibitors, incubation with purified furin, MMP inhibitors, incubation with recombinant MMP-2/8/15, heparin affinity chromatography, endothelial cell proliferation assay The Journal of biological chemistry High 10944521
2002 ADAMTS1 cleaves aggrecan at multiple sites including the Glu373-Ala site in the interglobular domain, classifying it as an aggrecanase. A point mutation in the zinc-binding domain abolishes catalytic activity; a furin-site mutant retains latency. ADAMTS1 is inhibited by TIMP-2 and TIMP-3 and by a specific monoclonal antibody. In vitro protease assay on ECM proteins, zinc-binding domain point mutagenesis, furin-site mutagenesis, peptide substrate activity assay, TIMP inhibition assay, monoclonal antibody neutralization Biochemical and biophysical research communications High 12054629
2003 ADAMTS1 inhibits VEGFR2 phosphorylation and endothelial cell proliferation by directly binding and sequestering VEGF165 via its C-terminal region. Binding requires the heparin-binding domain of VEGF165 (VEGF121, which lacks this domain, does not bind). The VEGF-ADAMTS1 complex is reversible, and active VEGF can be recovered. The complex was also detected in tumor extracts. Co-immunoprecipitation, chemical cross-linking, domain deletion analysis, VEGFR2 phosphorylation assay, endothelial cell proliferation assay, tumor extract co-IP The Journal of biological chemistry High 12716911
2003 ADAMTS1 protein localizes to cytoplasmic secretory vesicles as a 110 kDa pro-form in mural granulosa cells, and accumulates as an 85 kDa mature form in the extracellular matrix of the cumulus-oocyte complex (COC) during matrix expansion. ADAMTS1 cleaves versican in the expanded COC matrix, generating a 70 kDa N-terminal fragment (neoepitope DPEAAE). Versican cleavage is reduced in PRKO mouse ovaries lacking ADAMTS1 induction. Peptide antibodies against pro-domain and metalloprotease domain, immunofluorescence, Western blot, neoepitope immunodetection, progesterone receptor knockout (PRKO) mouse model The Journal of biological chemistry High 12907688
2004 ADAMTS1 gene transcription in granulosa cells is co-regulated by LH (via cAMP/PKA/CEBP-beta) and progesterone receptor (PR-A/B acting as an inducible coregulator). Three Sp1/Sp3 GC-rich binding sites, a nuclear factor 1-like site, and CEBP-beta sites in the proximal promoter are required; PR stimulates promoter activity without a consensus PR response element. Promoter-luciferase reporter assays with truncations and site-specific mutants, transfection in rat granulosa cells, PR antagonist (ZK98299), PRA/PRB co-transfection, cAMP analogs Molecular endocrinology High 15256533
2005 Fibulin-1 interacts with ADAMTS1 via the C-terminal region of ADAMTS1, as identified by yeast two-hybrid screening and confirmed by ligand affinity chromatography, co-immunoprecipitation, pulldown assays, and ELISA. Fibulin-1 acts as a cofactor, enhancing ADAMTS1-mediated cleavage of aggrecan without itself being a substrate. Yeast two-hybrid screen, ligand affinity chromatography, co-immunoprecipitation, pulldown assay, ELISA, in vitro aggrecan cleavage assay, in vivo co-localization The Journal of biological chemistry High 16061471
2005 ADAMTS1 is up-regulated in wounded skin; macrophages are the initial source, followed by keratinocytes and fibroblasts. At low concentrations, ADAMTS1 stimulates fibroblast migration via its proteolytic activity; at high concentrations it inhibits migration by binding FGF-2 and suppressing its pro-migratory activity. Similar dual effects are observed with endothelial cells. Immunofluorescence in wound tissue, ADAMTS1 knockout mouse skin phenotype, fibroblast/endothelial cell migration assays with recombinant ADAMTS1, protease-dead mutant, FGF-2 binding assays The Journal of biological chemistry High 15843381
2006 ADAMTS1 cleaves tissue factor pathway inhibitor-2 (TFPI-2), removing its protease-sensitive C-terminal region and altering its extracellular localization and binding properties. The interaction was identified by yeast two-hybrid screening and confirmed by biochemical and cell-based assays. Yeast two-hybrid screen, co-immunoprecipitation, biochemical cleavage assay, cell-based localization assay The Journal of biological chemistry Medium 16641089
2006 Proteomics (DIGE) identified nidogen-1, nidogen-2, desmocollin-3, dystroglycan-1, and Mac-2-binding protein as putative substrates of ADAMTS1 in conditioned medium; nidogen-1 and nidogen-2 were validated as cleavage substrates by immunochemical analysis. DIGE (2D difference gel electrophoresis), mass spectrometry, immunochemical validation, conditioned medium from ADAMTS1-overexpressing vs. parental cells Proteomics Medium 16511810
2006 ADAMTS1 promotes tumor metastasis through its metalloproteinase activity: overexpression of full-length ADAMTS1 (but not a protease-dead mutant) promotes pulmonary metastasis and tumor angiogenesis, sheds membrane-bound HB-EGF and amphiregulin (AR), and activates EGFR and ErbB-2. Autoproteolytic N- and C-terminal fragments of ADAMTS1 each inhibit metastasis and suppress Erk1/2 activation by soluble HB-EGF and AR. Overexpression of full-length vs. protease-dead ADAMTS1 mutant (E/Q) and cleavage fragments in tumor cell lines, pulmonary metastasis assay in mice, EGFR/ErbB-2 phosphorylation assay, EGF ligand shedding assay Oncogene High 16314835
2008 Endocardial Brg1 (a chromatin remodeling protein) represses ADAMTS1 expression in the endocardium overlying developing trabeculae. ADAMTS1, a secreted matrix metalloproteinase, degrades cardiac jelly components; its repression is required for trabecular growth. Later in embryogenesis, ADAMTS1 expression initiates in the endocardium to degrade cardiac jelly and limit excessive trabeculation. Genetic mouse models (Brg1 conditional knockout in endocardium), in vivo cardiac phenotyping, expression analysis Developmental cell High 18267097
2008 ADAMTS1 cleaves the ectodomain of syndecan-4, resulting in altered cytoskeletal organization, loss of focal adhesions, and increased cell migration. ADAMTS1 proteolytic action phenocopies genetic deletion of syndecan-4 with respect to focal adhesions. Recombinant ADAMTS1 cleavage of syndecan-4, syndecan-4 null cells, immunofluorescence of cytoskeletal components, focal adhesion assay, migration assay The international journal of biochemistry & cell biology High 18775505
2009 ADAMTS1 and MMP1 orchestrate a paracrine signaling cascade in bone metastasis: they proteolytically release membrane-bound EGF-like growth factors (AREG, HB-EGF, TGFα) from tumor cells, which suppress OPG expression in osteoblasts and potentiate osteoclast differentiation, promoting osteolytic bone metastasis. EGFR inhibitors block this cascade in bone stromal cells. Gain-of-function in tumor cell lines, conditioned medium transfer to osteoblasts, EGFR inhibitor treatment, osteoclast differentiation assay, 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 complementary proteomics approaches (DIGE and SILAC). DIGE and SILAC proteomics, recombinant ADAMTS1 overexpression, mass spectrometry substrate identification, breast cancer cell migration assay The Journal of biological chemistry Medium 19915008
2009 Hypoxia transiently induces ADAMTS1 mRNA and protein specifically in endothelial cells (not other cell types) via HIF-1 binding to at least three HIF binding sites in the ADAMTS1 promoter, as confirmed by chromatin immunoprecipitation. This induction is blocked by PI3K inhibitor LY294002. Recombinant ADAMTS1 promotes HUVEC migration under hypoxic conditions. Hypoxia and CoCl2 treatment, real-time PCR, Western blot, promoter-luciferase assay, chromatin immunoprecipitation (ChIP), PI3K inhibitor, cell migration assay The Journal of biological chemistry High 19349275
2010 ADAMTS1 cleaves thrombospondin-1 (TSP1), and this cleavage is organ-context-dependent: cleavage occurs more efficiently in liver than lung lysates, and ADAMTS1 inhibition (neutralizing antibody, siRNA, or genetic deletion) abrogates TSP1 cleavage. Differential ADAMTS1-mediated TSP1 processing underlies the variable anti-metastatic efficacy of TSP1 in liver vs. lung. [Note: this paper was retracted.] TSP1 cleavage assay in liver vs. lung lysates, neutralizing antibody, siRNA knockdown, Adamts1 knockout mice, metastasis models Cancer research Low 20103648
2011 ADAMTS1 is required for mammary tumor growth and metastasis in vivo: Adamts1 knockout in the MMTV-PyMT mouse model significantly reduces tumor burden and lung metastasis, with increased apoptosis and increased cytotoxic immune cell activation. Adamts1-null tumor stroma shows less proteolytically cleaved versican and increased CD45+ leukocyte infiltration. Adamts1 knockout mouse crossed with MMTV-PyMT mammary tumor model, histology, apoptosis assay, versican neoepitope immunostaining, immune cell phenotyping (IL-12, CD45) The American journal of pathology High 22001177
2012 In kidney pericytes, ADAMTS1 expression is rapidly activated after injury and contributes to microvascular destabilization, while TIMP3 (its inhibitor) stabilizes capillary tube networks. TIMP3-null mice show spontaneous microvascular phenotype with overactivated pericytes and increased susceptibility to injury-stimulated microvascular rarefaction. Gene expression profiling in kidney pericytes in vivo, 3D capillary tube assay, Timp3 knockout mouse, pericyte differentiation experiments Journal of the American Society of Nephrology : JASN High 22383695
2013 ADAMTS1 acts as a tumor suppressor in breast cancer xenografts by cleaving nidogen-1 and nidogen-2 from vascular basement membranes, disrupting vessel morphology and reducing vessel density. Increased ADAMTS1 expression causes near-complete inhibition of tumor growth and correlates with nidogen cleavage. Xenograft tumor model, ADAMTS1 overexpression, immunostaining for nidogens and vessels, microvessel density quantification International journal of cancer Medium 23681936
2014 ADAMTS1 inhibits lymphangiogenesis by forming a complex with VEGF-C and attenuating phosphorylation of VEGFR3 in lymphatic endothelial cells. Immunoprecipitation assays confirmed ADAMTS1-VEGF-C complex formation. Adenoviral ADAMTS1 gene transduction of lymphatic endothelial cells, cell proliferation assay, tube formation assay, migration assay, VEGFR3 phosphorylation assay, co-immunoprecipitation Experimental cell research Medium 24631293
2016 ADAMTS1 is required for SPARC-induced collagen deposition in aging myocardium. SPARC stimulation of cardiac fibroblasts increases secretion of both latent (110 kDa) and active (87 kDa) ADAMTS1 forms and promotes collagen I secretion; an ADAMTS1 blocking antibody suppresses SPARC-induced collagen I secretion. ADAMTS1 substrate versican decreases with age only in wild-type mice (not SPARC-null), linking SPARC-ADAMTS1 to proteoglycan turnover. SPARC-null mice, cardiac fibroblast stimulation with SPARC, ADAMTS1 blocking antibody, Western blot, picrosirius red staining, versican immunostaining American journal of physiology. Endocrinology and metabolism Medium 27143554
2016 Adamts1 metalloprotease activity impairs adipocyte commitment by remodeling ECM components and activating FAK-ERK signaling. miR-181d targets and represses Adamts1 to permit adipocytic lineage commitment. Ablation of Adamts1 in adipose tissue increases adipose mass and disrupts lipid homeostasis. The catalytic activity of Adamts1 is required for this inhibitory effect. Forced expression and siRNA knockdown of Adamts1, catalytic domain mutagenesis, adipogenesis differentiation assay, FAK-ERK signaling analysis, adipose-specific Adamts1 knockout mice, miR-181d target validation Cell death and differentiation High 27447109
2017 Macrophage-derived ADAMTS1 promotes satellite cell (muscle stem cell) activation by cleaving NOTCH1, thereby reducing Notch signaling. Overexpression of Adamts1 in macrophages in vivo is sufficient to increase satellite cell activation and improve muscle regeneration. NOTCH1 is identified as a direct substrate of ADAMTS1 metalloproteinase activity. Macrophage-specific Adamts1 overexpression in vivo, satellite cell activation assay, Notch signaling analysis, NOTCH1 substrate cleavage assay, muscle injury model Nature communications High 28939843
2017 Genetic haploinsufficiency of Adamts1 in mice causes thoracic aortic aneurysm and dissection (TAAD) associated with elevated aortic nitric oxide and Nos2 levels. Nos2 inactivation or pharmacological NOS2 inhibition protects Adamts1-deficient mice from aortic pathology and rapidly reverses aortic dilation and medial degeneration, placing ADAMTS1 upstream of the NOS2 axis in vascular homeostasis. Adamts1 haploinsufficient mice, Nos2 genetic knockout, NOS2 pharmacological inhibition, aortic histology and diameter measurement, nitric oxide quantification Nature medicine High 28067899
2020 ADAMTS1 and syndecan-4 are functionally interconnected in regulating endothelial cell adhesion, migration, and angiogenesis. Knockdown of ADAMTS1 in endothelial cells reduces cell-surface syndecan-4 levels via increased MMP9 activity. Both ADAMTS1 and syndecan-4 knockdowns enhance VEGFA164 responses and aortic ring sprouting. Fibulin-1, an ADAMTS1 co-factor, is absent from conditioned matrix of knockdown cells and correlates with altered migration. siRNA knockdown of ADAMTS1 and syndecan-4, MMP9 activity assay, VEGFA response assay, ex vivo aortic ring sprouting, conditioned matrix experiment, fibulin-1 expression analysis Journal of cell science Medium 32269093
2021 ADAMTS1 cleaves versican V1 at the canonical Glu441-Ala442 site and at multiple additional sites (21 novel sites with a P1-Glu preference), as determined by label-free quantitative LC-MS/MS proteomics comparing active vs. catalytically inactive ADAMTS1 digests of purified versican V1. In vitro digestion of recombinant versican V1 with recombinant ADAMTS1 vs. catalytically inactive mutant, LC-MS/MS, semi-tryptic peptide z-score analysis Journal of proteomics High 34450332
2006 VEGF upregulates ADAMTS1 expression in endothelial cells via VEGFR2 → phospholipase C-gamma → PKCbeta signaling. Knockdown of endogenous ADAMTS1 by siRNA increases endothelial cell proliferation, indicating ADAMTS1 is an endogenous brake on endothelial proliferation downstream of VEGF. VEGF stimulation, VEGFR2 and PLC-gamma inhibitors, PKC inhibitors (calphostin C, PKCbeta-specific inhibitor), siRNA knockdown, [3H]-thymidine incorporation proliferation assay Investigative ophthalmology & visual science High 16936124
2008 HDAC6 and SP1 repress ADAMTS1 transcription via proximal GC-box elements. HDAC inhibitors (TSA, SAHA) and HDAC6-specific inhibitor tubacin upregulate ADAMTS1 expression. ChIP and DAPA assays confirm decreased SP1 and HDAC6 binding to the ADAMTS1 promoter after TSA treatment. Promoter-luciferase reporter assay, ChIP (chromatin immunoprecipitation), DAPA (DNA affinity precipitation assay), HDAC inhibitors, HDAC6 knockdown, SP1 analysis FEBS letters Medium 19007777
2015 Ethanol increases O-GlcNAc modification of Adamts1 and decreases its interaction with endogenous inhibitor TIMP3 in myocytes, leading to increased collagen I and decreased elastin. Silencing Adamts1 by siRNA blocks ethanol-induced collagen/elastin changes. This is controlled upstream by FoxO1-sestrin3-AMPK signaling. siRNA knockdown of Adamts1, MMP pharmacological inhibition, O-GlcNAc modification detection, TIMP3 co-immunoprecipitation, FoxO1/AMPK pathway inhibitors, collagen/elastin quantification in C2C12 myocytes Journal of cellular biochemistry Medium 25142777

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2009 ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis. Genes & development 248 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 205 12716911
1976 Alternative pathway of complement: recruitment of precursor properdin by the labile C3/C5 convertase and the potentiation of the pathway. The Journal of experimental medicine 193 978134
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 169 22383695
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 145 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
1999 ADAMTS-1 is an active metalloproteinase associated with the extracellular matrix. The Journal of biological chemistry 131 10373500
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 126 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 124 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 110 28939843
2004 Coordinate transcription of the ADAMTS-1 gene by luteinizing hormone and progesterone receptor. Molecular endocrinology (Baltimore, Md.) 106 15256533
2011 Design and development of TT30, a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases. Blood 105 21860027
2005 Fibulin-1 acts as a cofactor for the matrix metalloprotease ADAMTS-1. The Journal of biological chemistry 90 16061471
2003 ADAMTS1: a matrix metalloprotease with angioinhibitory properties. Annals of the New York Academy of Sciences 88 12814950
2009 The cleavage of semaphorin 3C induced by ADAMTS1 promotes cell migration. The Journal of biological chemistry 87 19915008
2005 The expression and regulation of ADAMTS-1, -4, -5, -9, and -15, and TIMP-3 by TGFbeta1 in prostate cells: relevance to the accumulation of versican. The Prostate 87 15599946
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
2013 The metalloproteinase ADAMTS1: a comprehensive review of its role in tumorigenic and metastatic pathways. International journal of cancer 67 23444028
2008 Cleavage of syndecan-4 by ADAMTS1 provokes defects in adhesion. The international journal of biochemistry & cell biology 67 18775505
2018 Functional Characterization of Alternative and Classical Pathway C3/C5 Convertase Activity and Inhibition Using Purified Models. Frontiers in immunology 64 30083158
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 64 20598569
2011 The ADAMTS1 protease gene is required for mammary tumor growth and metastasis. The American journal of pathology 63 22001177
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
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 61 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 53 16511810
2013 Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion. Molecular cancer 51 23289900
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
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 51 15983115
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 49 32719126
2013 Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: differential regulation by key cytokines implicated in atherosclerosis and novel synergism between TL1A and IL-17. Cytokine 49 23859810
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
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 44 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
1989 A properdin dependent nephritic factor slowly activating C3, C5, and C9 in membranoproliferative glomerulonephritis, types I and III. Clinical immunology and immunopathology 42 2917424
2021 Pan-Cancer Analysis of Immune Complement Signature C3/C5/C3AR1/C5AR1 in Association with Tumor Immune Evasion and Therapy Resistance. Cancers 40 34439277
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) 40 16675485
2020 ADAMTS-1 and syndecan-4 intersect in the regulation of cell migration and angiogenesis. Journal of cell science 39 32269093
2014 Evidence for decreased expression of ADAMTS-1 associated with impaired oocyte quality in PCOS patients. The Journal of clinical endocrinology and metabolism 39 24646063
2013 ADAMTS1, ADAMTS5, ADAMTS9 and aggrecanase-generated proteoglycan fragments are induced following spinal cord injury in mouse. Neuroscience letters 39 23562508
2008 Association between ADAMTS1 matrix metalloproteinase gene variation, coronary heart disease, and benefit of statin therapy. Arteriosclerosis, thrombosis, and vascular biology 39 18174457
2021 Identification of novel ADAMTS1, ADAMTS4 and ADAMTS5 cleavage sites in versican using a label-free quantitative proteomics approach. Journal of proteomics 38 34450332
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
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 38 23681936
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
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
2005 Differential expression of genes coding for EGF-like factors and ADAMTS1 following gonadotropin stimulation in normal and transformed human granulosa cells. Biochemical and biophysical research communications 32 15967414
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
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
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
2009 Stringent regulation of complement lectin pathway C3/C5 convertase by C4b-binding protein (C4BP). Molecular immunology 27 19660812
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
2009 ADAMTS1, a putative anti-angiogenic factor, is decreased in human prostate cancer. BJU international 25 19522863
2019 ADAMTS-1 inhibits angiogenesis via the PI3K/Akt-eNOS-VEGF pathway in lung cancer cells. Translational cancer research 24 35117030
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
2018 ADAMTS1 protease is required for a balanced immune cell repertoire and tumour inflammatory response. Scientific reports 22 30166561
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 miR-365b-3p inhibits the cell proliferation and migration of human coronary artery smooth muscle cells by directly targeting ADAMTS1 in coronary atherosclerosis. Experimental and therapeutic medicine 21 30402161
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
2020 ADAMTS1 and HSPG2 mRNA levels in cumulus cells are related to human oocyte quality and controlled ovarian hyperstimulation outcomes. Journal of assisted reproduction and genetics 20 31974739
2016 The impact of parathyroidectomy on serum ADAMTS1, ADAMTS4 levels, insulin resistance, and subclinical cardiovascular disease in primary hyperparathyroidism. Endocrine 20 27844209
2012 Expression of ADAMTS-1, ADAMTS-4, ADAMTS-5 and TIMP3 by hepatocellular carcinoma cell lines. International journal of oncology 20 22735305
2006 ADAMTS1 is regulated by interleukin-1beta, not by hypoxia, in chondrosarcoma. Human pathology 20 16949904
2017 ADAMTS-1 in abdominal aortic aneurysm. PloS one 19 28570682

Missed literature

Know a paper Affinage missed for ADAMTS1? Flag it for the maintainers and the community.

No submissions yet.