Affinage

ADAMTS9

A disintegrin and metalloproteinase with thrombospondin motifs 9 · UniProt Q9P2N4

Length
1935 aa
Mass
216.5 kDa
Annotated
2026-06-09
100 papers in source corpus 26 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADAMTS9 is a secreted zinc metalloprotease that remodels the pericellular and extracellular matrix to control cardiovascular, gonadal, skeletal, and vascular development (PMID:20096780, PMID:26027930, PMID:30951722). It is synthesized as a zymogen that is secreted intact and processed at the cell surface by furin (and PC5A) at the Arg287-Phe288 bond rather than intracellularly (PMID:12514189, PMID:16537537); its propeptide acts as an intramolecular chaperone requiring N-linked glycosylation for secretion, and—paradoxically—furin processing reduces rather than activates catalytic activity, with cleaved propeptide fragments remaining non-covalently associated with the catalytic domain (PMID:17403680). Cell-surface processing is organized by the chaperones GRP94/gp96 and BiP, which form a complex with pro-ADAMTS9 and furin (PMID:19875450), while secretion additionally requires POFUT2-mediated O-fucosylation and B3GLCT-mediated glucosylation of its thrombospondin type 1 repeats (PMID:27297885, PMID:31600785). The ancillary (TSR-containing) domains, not the catalytic domain alone, are required for cell-surface localization and substrate cleavage (PMID:12514189). Active ADAMTS9 cleaves matrix proteoglycans—versican and aggrecan (the latter at E↓G bonds distinct from ADAMTS-4/5) (PMID:17403680, PMID:20096780, PMID:30699963)—as well as fibronectin at Gly2196-Leu2197 (PMID:31085586) and the transmembrane metalloprotease MT1-MMP in its hinge and hemopexin domains, limiting MT1-MMP surface retention and pro-MMP2 activation (PMID:37169079). Through pericellular versican proteolysis ADAMTS9 maintains focal adhesions upstream of cytoskeletal assembly and smooth muscle cell differentiation, drives PDGFRβ/ERK and Hedgehog signaling, supports primary cilium biogenesis, and is required for myometrial activation and parturition (PMID:26027930, PMID:29642006, PMID:37035301, PMID:37169079); it also acts cell-autonomously as an angiogenesis inhibitor through its catalytic activity (PMID:20093484). Independent of protease function, its C-terminal GON domain promotes ER-to-Golgi protein transport (PMID:22419820). Expression is induced by IL-1β/TNFα via MAPK signaling and NFATc1-mediated transcription (PMID:15880812, PMID:19052845), attenuated by mechanical strain through TRPV1-dependent suppression of NF-κB (PMID:31415758), and silenced in cancers by DNMT3A-driven promoter hypermethylation or METTL3/YTHDF2-dependent mRNA degradation (PMID:33931579, PMID:35574388).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2003 High

    Established how the latent zymogen becomes active and which regions are needed, answering whether the catalytic domain alone suffices for proteoglycan cleavage.

    Evidence Pulse-chase, site-directed mutagenesis, and amino acid sequencing in transfected cells with proteolytic assays

    PMID:12514189

    Open questions at the time
    • Did not resolve where processing occurs (intra- vs. extracellular)
    • Mechanism by which TSR-containing ancillary domains direct localization not defined
  2. 2006 High

    Resolved the cellular location of activation, showing the zymogen is secreted intact and processed at the cell surface rather than within the secretory pathway.

    Evidence Pulse-chase with PC inhibitors, furin-deficient cells, furin rescue, and furin siRNA

    PMID:16537537

    Open questions at the time
    • Functional consequence of surface processing not yet linked to activity change
    • Chaperones organizing surface processing unknown
  3. 2007 High

    Reframed propeptide processing as a secretion/chaperone requirement rather than an activation step, since furin cleavage reduced catalytic activity.

    Evidence Mutagenesis of N-glycosylation and furin sites with versican cleavage assays

    PMID:17403680

    Open questions at the time
    • Structural basis of propeptide retention on catalytic domain unresolved
    • Physiological trigger that fully activates the enzyme not identified
  4. 2009 High

    Identified the chaperone machinery coordinating surface processing, explaining how an ER chaperone influences extracellular furin cleavage.

    Evidence Cross-linking/MS, reciprocal co-IP, geldanamycin, and gp96/BiP siRNA with functional readout

    PMID:19875450

    Open questions at the time
    • How an ER chaperone reaches the cell surface not mechanistically defined
    • Stoichiometry of the pro-ADAMTS9/furin/gp96 complex unknown
  5. 2016 High

    Demonstrated that TSR glycosylation is a gatekeeper for secretion, linking a glycosyltransferase to ADAMTS9 trafficking and developmental requirement.

    Evidence CRISPR POFUT2 knockout secretion assay plus conditional Pofut2/Adamts9 deletion epistasis

    PMID:27297885

    Open questions at the time
    • Whether other TSR modifications act redundantly not fully resolved
    • Substrate repertoire affected by secretion failure not mapped
  6. 2010 High

    Provided the first in vivo evidence that versican proteolysis by ADAMTS9 is required for normal cardiovascular structure.

    Evidence Adamts9+/LacZ haploinsufficient mice with versican and cleaved-versican immunostaining

    PMID:20096780

    Open questions at the time
    • Cell types responsible for cardiovascular phenotype not delineated here
    • Downstream signaling consequences of versican accumulation not addressed
  7. 2010 High

    Defined ADAMTS9 as a catalytically dependent endothelial angiogenesis inhibitor distinct in mechanism from ADAMTS1.

    Evidence siRNA, active vs. inactive overexpression, tube formation/migration assays, and ADAMTS9+/- tumor model

    PMID:20093484 PMID:20551050

    Open questions at the time
    • Endothelial substrate driving anti-angiogenic effect not identified
    • Relationship between ECM cleavage and VEGFA/MMP9 changes correlative
  8. 2015 High

    Connected versican proteolysis to vascular smooth muscle morphogenesis and primary cilium-linked signaling, moving from substrate accumulation to downstream pathways.

    Evidence Adamts9 gene trap and conditional deletion mice with PDGFRβ/ERK, Shh, and cilium readouts

    PMID:26027930

    Open questions at the time
    • Direct molecular link between versican turnover and ciliary signaling unclear
    • Whether ECM cleavage products signal directly not established
  9. 2018 High

    Placed pericellular versican proteolysis upstream of focal adhesion maintenance and SMC differentiation, providing an epistatic mechanism for the tissue phenotype.

    Evidence Conditional uterine SMC Adamts9 deletion with versican knockdown rescue and parturition analysis

    PMID:29642006

    Open questions at the time
    • Receptor reading versican accumulation to focal adhesions not identified here
    • Generalizability beyond uterine SMC untested
  10. 2019 High

    Expanded the substrate repertoire beyond proteoglycans by identifying fibronectin as a direct binding partner and cleavage target affecting matrix fibril assembly.

    Evidence Yeast two-hybrid, SPR/solid-phase binding, fibril disruption, ADAMTS9-deficient cells, and LC-MS cleavage-site mapping

    PMID:31085586

    Open questions at the time
    • In vivo relevance of fibronectin cleavage not yet demonstrated
    • Which phenotypes depend on fibronectin vs. proteoglycan substrates unresolved
  11. 2012 Medium

    Revealed a protease-independent intracellular role in ER-to-Golgi transport mediated by the GON domain, broadening ADAMTS9 function beyond ECM proteolysis.

    Evidence ADAMTS9 siRNA, GON-domain rescue constructs, transport assays, and C. elegans GON-1 genetics

    PMID:22419820 PMID:26218657

    Open questions at the time
    • Molecular partners of the GON domain in transport unknown
    • Relationship between secretory function and extracellular protease role unclear
  12. 2023 High

    Identified MT1-MMP as a transmembrane substrate, linking ADAMTS9 to control of cell-surface metalloprotease activity and ciliogenesis versus focal adhesions.

    Evidence TAILS degradomics, gene-edited RPE-1 cells, re-expression, shedding/pro-MMP2 assays, and MT1-MMP siRNA epistasis

    PMID:37169079

    Open questions at the time
    • Why MT1-MMP knockdown rescues focal adhesions but not ciliogenesis unexplained
    • In vivo significance of MT1-MMP cleavage not established
  13. 2019 Medium

    Linked ADAMTS9 to metabolic regulation, showing muscle-specific gain and loss of function alter integrin β1 signaling and insulin sensitivity in line with a human risk allele.

    Evidence Muscle-specific knockout/overexpression mice with clamp studies and human eQTL association

    PMID:30626608

    Open questions at the time
    • Direct substrate mediating integrin β1 signaling changes unidentified
    • Causality of human risk-allele association limited to correlation
  14. 2021 Medium

    Characterized epigenetic and post-transcriptional silencing of ADAMTS9 in cancer, defining how its tumor-suppressive expression is lost.

    Evidence Re-expression with RNA-seq, DNMT3A/RNF180 manipulation and methylation analysis; METTL3/YTHDF2 mRNA-stability and PI3K/AKT rescue assays

    PMID:33931579 PMID:35574388

    Open questions at the time
    • Whether nuclear ADAMTS9 enrichment reflects a direct function unresolved
    • Substrate basis of tumor suppression in these cancers not defined
  15. 2023 Medium

    Modeled the ciliary requirement in a human system, tying ADAMTS9 loss to reduced primary cilia and altered Wnt/PCP signaling in kidney cell types.

    Evidence ADAMTS9-knockout hiPSC kidney organoids with single-cell RNA-seq and cilia quantification

    PMID:37035301

    Open questions at the time
    • Substrate driving ciliary defect in organoids not identified
    • Direct vs. indirect effect on Wnt/PCP signaling unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ADAMTS9's distinct activities—ECM proteolysis, MT1-MMP regulation, and GON-domain-mediated secretion—are integrated to produce specific developmental and disease phenotypes remains unresolved.
  • No unifying structural model connecting domains to substrate selection
  • The receptor/effector that translates ECM cleavage into focal adhesion and ciliary signaling is unidentified
  • In vivo relevance of fibronectin and MT1-MMP cleavage not tested in mammals

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 3
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 3 GO:0031012 extracellular matrix 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1474244 Extracellular matrix organization 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-5653656 Vesicle-mediated transport 1
Partners
B3GLCTFN1FURINHSP90B1HSPA5MMP14PCSK5POFUT2

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 ADAMTS9 is activated by selective proprotein convertase (furin) cleavage at the Arg287-Phe288 bond, as demonstrated by pulse-chase analysis, site-directed mutagenesis, and amino acid sequencing. The ancillary domains (including TSRs) are required for cell-surface localization and for versicanase/aggrecanase activity; the catalytic domain alone is insufficient. Pulse-chase analysis, site-directed mutagenesis, amino acid sequencing, cell transfection with proteolytic activity assays The Journal of biological chemistry High 12514189
2006 Pro-ADAMTS9 zymogen is not processed intracellularly but is secreted intact to the cell surface, where furin cleaves the propeptide extracellularly. This cell-surface furin-dependent processing was demonstrated by PC inhibitors, furin-deficient cells, furin rescue, and furin siRNA knockdown. PC5A can also process pro-ADAMTS9 but likewise only extracellularly. Pulse-chase analysis, PC inhibitors, furin-deficient cell lines, furin rescue, furin siRNA The Journal of biological chemistry High 16537537
2007 The ADAMTS9 propeptide functions as an intramolecular chaperone required for secretion: N-linked glycosylation at three consensus sites in the propeptide is essential for secretion. Furin processing at three sites (Arg74, Arg209, Arg287) paradoxically reduces rather than activates catalytic activity, with propeptide fragments retaining non-covalent association with the catalytic domain after processing. Site-directed mutagenesis of N-glycosylation and furin cleavage sites, pulse-chase, versican cleavage assays, proprotein convertase inhibitor treatment The Journal of biological chemistry High 17403680
2009 Cell-surface processing of pro-ADAMTS9 is regulated by the ER chaperone GRP94/gp96, which forms an immunoprecipitable complex with pro-ADAMTS9 and furin at the cell surface. Geldanamycin (gp96/HSP90 inhibitor) decreases furin processing of pro-ADAMTS9; gp96 siRNA reduces cell-surface pro-ADAMTS9 and furin; BiP siRNA reduces cell-surface pro-ADAMTS9 but not furin. Cross-linking/mass spectrometry, co-immunoprecipitation, geldanamycin treatment, gp96 and BiP siRNA knockdown The Journal of biological chemistry High 19875450
2010 ADAMTS9 haploinsufficiency in mice leads to reduced versican cleavage and accumulation of versican in the aortic wall and cardiac valves, demonstrating that ADAMTS9-mediated versican proteolysis is required for normal cardiovascular development and homeostasis. Adamts9+/LacZ mouse model, immunostaining for versican and cleaved versican, beta-galactosidase staining, histological analysis Matrix biology High 20096780
2010 ADAMTS9 is expressed cell-autonomously in microvascular endothelial cells and acts as an angiogenesis inhibitor through its proteolytic activity: ADAMTS9 siRNA in human microvascular ECs increases filopodia, migration, and tube formation; catalytically active (but not inactive) ADAMTS9 overexpression reduces tube formation. Unlike ADAMTS1, ADAMTS9 neither cleaves thrombospondins 1/2 nor binds VEGF165. siRNA knockdown, overexpression of active vs. catalytically inactive ADAMTS9, tube formation/Matrigel assay, cell migration assay, heterotopic tumor model in ADAMTS9+/- mice The American journal of pathology High 20093484
2010 ADAMTS9 suppresses tumor formation and angiogenesis in esophageal squamous cell carcinoma and nasopharyngeal carcinoma; ADAMTS9 re-expression reduces microvessel numbers in Matrigel plugs and reduces tube formation by HUVECs, associated with reduced MMP9 and VEGFA expression. Tumorigenicity assays in nude mice, in vivo Matrigel plug angiogenesis assay, conditioned medium HUVEC tube formation assay, VEGFA/MMP9 expression analysis Cancer research Medium 20551050
2005 IL-1β and TNFα synergistically induce ADAMTS9 mRNA and protein expression in OUMS-27 chondrosarcoma cells and human chondrocytes, and this induction is mediated through the MAPK signaling pathway (p38 and MEK1/2 inhibitors SB203580 and PD98059 decrease upregulation). qRT-PCR, Northern blotting, Western blotting, pharmacological MAPK inhibitors in cytokine-stimulated cells Arthritis and rheumatism Medium 15880812
2008 IL-1β-induced ADAMTS9 expression in chondrocytes is transcriptionally regulated by NFATc1, which binds directly to distal and proximal promoter elements of ADAMTS9, as shown by chromatin immunoprecipitation, promoter-reporter assays, and inhibition by FK506 and 11R-VIVIT. Promoter cloning, chromatin immunoprecipitation (ChIP), luciferase reporter assays, NFAT inhibitors (FK506, 11R-VIVIT), qRT-PCR Molecular and cellular biochemistry Medium 19052845
2015 ADAMTS9 produced by mesenchymal cells is required for umbilical vascular smooth muscle cell proliferation, differentiation, and orthogonal rotation by mediating versican proteolysis and ECM dynamics. Loss of ADAMTS9 impairs PDGFRβ/MAPK-ERK signaling and disrupts Shh signaling and primary cilium orientation in mesenchymal cells. Adamts9 gene trap (Gt) allele mice, conditional Adamts9 deletion, immunostaining for versican cleavage products, PDGFRβ/ERK pathway analysis, Shh signaling analysis, primary cilium imaging Cell reports High 26027930
2018 ADAMTS9 proteolytic cleavage of pericellular versican is required to maintain focal adhesions in uterine smooth muscle cells. Versican knockdown or exogenous versican proteolysis rescues focal adhesion phenotype caused by ADAMTS9 depletion; pericellular versican accumulation acts upstream of cytoskeletal assembly and SMC differentiation. ADAMTS9 is required for myometrial activation and parturition in mice. Conditional Adamts9 deletion in uterine SMC, ADAMTS9 siRNA knockdown, versican siRNA, exogenous versican proteolysis, focal adhesion immunostaining, parturition phenotype analysis Cell reports High 29642006
2016 POFUT2-mediated O-fucosylation of ADAMTS9 thrombospondin type 1 repeats is required for ADAMTS9 secretion. CRISPR/Cas9 knockout of POFUT2 in HEK293T cells blocks ADAMTS9 secretion. Conditional deletion evidence shows that loss of ADAMTS9 in extra-embryonic tissues (not epiblast) is responsible for gastrulation defects in Pofut2 mutants. CRISPR/Cas9 knockout of POFUT2 in HEK293T cells, Cre-mediated conditional deletion of Pofut2 and Adamts9, comparison of knockout phenotypes, ADAMTS9 secretion assay Developmental biology High 27297885
2019 ADAMTS9 binds fibronectin through multiple sites identified by yeast two-hybrid and confirmed by solid-phase binding assays and surface plasmon resonance. Catalytically active ADAMTS9 disrupts fibronectin fibril networks formed by fibroblasts; ADAMTS9-deficient RPE1 cells assemble a more robust fibronectin network. LC-MS identified a cleavage site at Gly2196-Leu2197 in the linker between fibronectin modules III17 and I10. Yeast two-hybrid screen, solid-phase binding assay, surface plasmon resonance, fibronectin fibril disruption assay, ADAMTS9-deficient cell lines, targeted LC-MS of fibronectin cleavage products The Journal of biological chemistry High 31085586
2012 ADAMTS9 (and its C. elegans ortholog GON-1) has a novel intracellular function in promoting ER-to-Golgi protein transport, mediated by its C-terminal GON domain and independent of its protease activity. Knockdown of ADAMTS9 in human cells inhibits this transport, and the GON domain expressed in the ER rescues the phenotype. siRNA knockdown of ADAMTS9 in human cells, expression of GON domain constructs, ER-to-Golgi transport assays, C. elegans GON-1 loss-of-function genetics Molecular biology of the cell Medium 22419820
2019 ADAMTS9 overexpression in skeletal muscle impairs insulin signaling through alterations in the integrin β1 signaling pathway and cytoskeletal organization, and leads to mitochondrial dysfunction. Mice lacking Adamts9 selectively in skeletal muscle have improved insulin sensitivity. The ADAMTS9 rs4607103 C risk allele is associated with increased ADAMTS9 expression and decreased insulin sensitivity in human skeletal muscle. Muscle-specific Adamts9 knockout mice (insulin clamp studies), ADAMTS9 overexpression in skeletal muscle, integrin β1 and cytoskeletal marker analysis, mitochondrial function assays, human genetic association with expression data Diabetes Medium 30626608
2015 In C. elegans, loss of GON-1 (ADAMTS9 ortholog) impairs secretion of insulin orthologs and TGF-β, alters insulin/IGF-1 signaling in peripheral tissues, and affects lifespan and dauer formation. These functions require the GON domain but not the protease domain. C. elegans GON-1 loss-of-function genetics, protein secretion assays, dauer/lifespan phenotype analysis, domain rescue experiments PloS one Medium 26218657
2019 In mouse cartilage lacking ADAMTS-4 and ADAMTS-5 catalytic activity, ADAMTS-9 is upregulated by retinoic acid and cleaves aggrecan at E↓G bonds (rather than the E↓A bonds cleaved by ADAMTS-4/5), demonstrating a distinct aggrecanase specificity for ADAMTS-9 that may support normal skeletal development. Microarray of TS-4/5Δcat mouse cartilage explants, immunohistochemistry for ADAMTS-9 in growth plate, aggrecan cleavage site analysis International journal of molecular sciences Medium 30699963
2023 ADAMTS9 (and ADAMTS20) cleaves membrane type 1-matrix metalloproteinase (MT1-MMP) at Tyr314-Gly315 in the hinge region (between catalytic and hemopexin domains) and at a second site in the hemopexin domain, dependent on hinge O-glycosylation. Loss of ADAMTS9/20 increases MT1-MMP retention on the cell surface and increases pro-MMP2 activation. MT1-MMP knockdown in ADAMTS9/20-deficient cells restores focal adhesions but not ciliogenesis. Quantitative terminomics (TAILS), gene-edited RPE-1 cells lacking ADAMTS9, re-expression of ADAMTS9/ADAMTS20, MT1-MMP ectodomain shedding assay, pro-MMP2 activation assay, MT1-MMP siRNA epistasis Molecular & cellular proteomics High 37169079
2021 ADAMTS9 expression is silenced in gastric cancer by DNMT3A-mediated promoter hypermethylation; RNF180 ubiquitinates DNMT3A leading to its proteasomal degradation, thereby restoring ADAMTS9 expression. Restored ADAMTS9 expression suppresses GC cell viability and motility. ADAMTS9 is enriched in the nuclei of gastric mucosal cells and significantly alters gene expression profiles. ADAMTS9 re-expression in gastric cancer cells, RNA-sequencing, DNMT3A and RNF180 manipulation, ubiquitination assay, methylation analysis Cell death & disease Medium 33931579
2022 METTL3-mediated m6A RNA modification leads to YTHDF2-dependent degradation of ADAMTS9 mRNA in gastric cancer, suppressing ADAMTS9 protein levels and facilitating angiogenesis and carcinogenesis via the ADAMTS9-mediated PI3K/AKT pathway. METTL3 overexpression/knockdown, phenotypic assays, YTHDF2-dependent mRNA stability assays, ADAMTS9 rescue experiments, PI3K/AKT pathway analysis Frontiers in oncology Medium 35574388
2019 In zebrafish, gonadotropin (hCG/LH analog) induces adamts9 expression in preovulatory follicles via Lhcgr and its associated cAMP and PKC signaling pathways, as shown by dose-response, lhcgr-/- and pgr-/- zebrafish follicle experiments. hCG dose-response in zebrafish follicles in vitro, lhcgr-/- and pgr-/- zebrafish genetic models, cAMP and PKC pathway inhibitors Molecular and cellular endocrinology Medium 31586455
2019 Adamts9 is required for ovarian development and ovulation in zebrafish; adamts9-/- female fish have small ovaries with few mature oocytes, and no ovulated oocytes were observed, establishing ADAMTS9 as necessary for oocyte maturation/ovulation. CRISPR/Cas9 adamts9 knockout zebrafish, histological examination of gonads General and comparative endocrinology Medium 30951722
2018 ENU-induced dominant Adamts9 mutations (Und3 and Und4) cause loss of melanocytes in the mouse tail epidermis at ~E18.5, with evidence for a cell-autonomous requirement in melanocytes. TAILS N-terminomics proteomics identified new candidate ADAMTS9 substrates in skin ECM. ENU mutagenesis, conditional Adamts9 allele, TAILS N-terminomics proteomics of skin ECM Pigment cell & melanoma research Medium 29781574
2019 Mechanical strain attenuates cytokine-induced ADAMTS9 expression in chondrocytes via the mechanosensitive TRPV1 channel, which inhibits NF-κB translocation to the nucleus; TRPV1 pharmacological inhibitors and siRNA abolish this effect. Cyclic tensile strain on chondrocytes, TRPV1 pharmacological inhibitors (gadolinium, ruthenium red), TRPV1 siRNA, NF-κB nuclear translocation assay, qRT-PCR Experimental cell research Medium 31415758
2023 ADAMTS9 knockout in kidney organoids derived from human iPSCs reduces the number of primary cilia, recapitulating renal ciliopathy. Single-cell transcriptomics show highest ADAMTS9 expression in podocytes and proximal tubules; loss increases Wnt/PCP signaling activity in podocyte clusters. ADAMTS9 knockout hiPSC-derived kidney organoids, single-cell RNA sequencing, primary cilia quantification Frontiers in medicine Medium 37035301
2019 ADAMTS9 conditional deletion in mouse uterine smooth muscle cells demonstrates a requirement for myometrial activation and parturition, acting through pericellular versican proteolysis to maintain focal adhesions upstream of cytoskeletal assembly and SMC differentiation. Conditional Adamts9 deletion in uterine SMC (Cre-lox), versican immunostaining, focal adhesion marker analysis, parturition phenotype Cell reports High 29642006
2019 B3GLCT (β3-glucosyltransferase) inactivation differentially affects ADAMTS9 and ADAMTS20 function; ADAMTS9 is partially reduced (not abolished) by B3GLCT loss, causing eye abnormalities and contributing to cleft palate in mice, whereas white spotting and hydrocephalus arise from ADAMTS20 loss. B3glct knockout mouse alleles, genetic rescue experiments, biochemical secretion assays for ADAMTS9 and ADAMTS20 Human molecular genetics Medium 31600785

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Characterization of ADAMTS-9 and ADAMTS-20 as a distinct ADAMTS subfamily related to Caenorhabditis elegans GON-1. The Journal of biological chemistry 273 12514189
2020 LncRNA ADAMTS9-AS2 inhibits gastric cancer (GC) development and sensitizes chemoresistant GC cells to cisplatin by regulating miR-223-3p/NLRP3 axis. Aging 141 32516127
2010 Reduced versican cleavage due to Adamts9 haploinsufficiency is associated with cardiac and aortic anomalies. Matrix biology : journal of the International Society for Matrix Biology 128 20096780
2008 Association testing of novel type 2 diabetes risk alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity, and obesity in a population-based sample of 4,516 glucose-tolerant middle-aged Danes. Diabetes 121 18567820
2014 A new tumor suppressor LncRNA ADAMTS9-AS2 is regulated by DNMT1 and inhibits migration of glioma cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 112 24833086
2009 Gene variants in the novel type 2 diabetes loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B affect different aspects of pancreatic beta-cell function. Diabetes 106 19833888
2005 Adamts9 is widely expressed during mouse embryo development. Gene expression patterns : GEP 85 15939373
2019 Novel Function of lncRNA ADAMTS9-AS2 in Promoting Temozolomide Resistance in Glioblastoma via Upregulating the FUS/MDM2 Ubiquitination Axis. Frontiers in cell and developmental biology 84 31632968
2010 ADAMTS9 is a cell-autonomously acting, anti-angiogenic metalloprotease expressed by microvascular endothelial cells. The American journal of pathology 84 20093484
2000 ADAMTS9, a novel member of the ADAM-TS/ metallospondin gene family. Genomics 82 10936055
2005 ADAMTS-9 is synergistically induced by interleukin-1beta and tumor necrosis factor alpha in OUMS-27 chondrosarcoma cells and in human chondrocytes. Arthritis and rheumatism 81 15880812
2018 Upregulated lncRNA ADAMTS9-AS2 suppresses progression of lung cancer through inhibition of miR-223-3p and promotion of TGFBR3. IUBMB life 78 29707897
2018 LncRNA ADAMTS9-AS2 regulates ovarian cancer progression by targeting miR-182-5p/FOXF2 signaling pathway. International journal of biological macromolecules 72 30268751
2010 Extracellular protease ADAMTS9 suppresses esophageal and nasopharyngeal carcinoma tumor formation by inhibiting angiogenesis. Cancer research 72 20551050
2018 Upregulation of lncRNA ADAMTS9-AS2 Promotes Salivary Adenoid Cystic Carcinoma Metastasis via PI3K/Akt and MEK/Erk Signaling. Molecular therapy : the journal of the American Society of Gene Therapy 66 30217729
2014 Leptin induces ADAMTS-4, ADAMTS-5, and ADAMTS-9 genes expression by mitogen-activated protein kinases and NF-ĸB signaling pathways in human chondrocytes. Cell biology international 65 25045124
2006 Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9. Oncogene 62 16799631
2020 Long non-coding RNA ADAMTS9-AS1 suppresses colorectal cancer by inhibiting the Wnt/β-catenin signalling pathway and is a potential diagnostic biomarker. Journal of cellular and molecular medicine 57 32889785
2006 Cell-surface processing of pro-ADAMTS9 by furin. The Journal of biological chemistry 56 16537537
2019 LncRNA ADAMTS9-AS2 promotes tongue squamous cell carcinoma proliferation, migration and EMT via the miR-600/EZH2 axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 52 30970517
2007 Regulation of ADAMTS9 secretion and enzymatic activity by its propeptide. The Journal of biological chemistry 52 17403680
2019 LncRNA ADAMTS9-AS2 inhibits cell proliferation and decreases chemoresistance in clear cell renal cell carcinoma via the miR-27a-3p/FOXO1 axis. Aging 50 31400752
2015 ADAMTS9-Mediated Extracellular Matrix Dynamics Regulates Umbilical Cord Vascular Smooth Muscle Differentiation and Rotation. Cell reports 50 26027930
2021 lncRNA ADAMTS9-AS1 promotes bladder cancer cell invasion, migration, and inhibits apoptosis and autophagy through PI3K/AKT/mTOR signaling pathway. The international journal of biochemistry & cell biology 48 34428588
2008 Characterization of a novel epigenetically-silenced, growth-suppressive gene, ADAMTS9, and its association with lymph node metastases in nasopharyngeal carcinoma. International journal of cancer 48 18449890
2018 ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent Smooth Muscle Differentiation. Cell reports 45 29642006
2009 Variant near ADAMTS9 known to associate with type 2 diabetes is related to insulin resistance in offspring of type 2 diabetes patients--EUGENE2 study. PloS one 45 19789630
2019 Downregulated lncRNA ADAMTS9-AS2 in breast cancer enhances tamoxifen resistance by activating microRNA-130a-5p. European review for medical and pharmacological sciences 44 30840279
2019 Long noncoding RNA ADAMTS9-AS2 suppresses the progression of esophageal cancer by mediating CDH3 promoter methylation. Molecular carcinogenesis 44 31621118
2020 Data Mining and Expression Analysis of Differential lncRNA ADAMTS9-AS1 in Prostate Cancer. Frontiers in genetics 43 32153626
2018 RETRACTED: Down-regulation of lncRNA ADAMTS9-AS2 contributes to gastric cancer development via activation of PI3K/Akt pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 43 30089248
2020 Exosome-derived long non-coding RNA ADAMTS9-AS2 suppresses progression of oral submucous fibrosis via AKT signalling pathway. Journal of cellular and molecular medicine 41 33345447
2008 ADAMTS9 activation by interleukin 1 beta via NFATc1 in OUMS-27 chondrosarcoma cells and in human chondrocytes. Molecular and cellular biochemistry 40 19052845
2022 Long non-coding RNA ADAMTS9-AS1 attenuates ferroptosis by Targeting microRNA-587/solute carrier family 7 member 11 axis in epithelial ovarian cancer. Bioengineered 39 35311457
2016 Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion. Developmental biology 39 27297885
2013 ADAMTS1, ADAMTS5, ADAMTS9 and aggrecanase-generated proteoglycan fragments are induced following spinal cord injury in mouse. Neuroscience letters 39 23562508
2019 lncRNA ADAMTS9-AS2 Controls Human Mesenchymal Stem Cell Chondrogenic Differentiation and Functions as a ceRNA. Molecular therapy. Nucleic acids 37 31671346
2009 Cell-surface processing of the metalloprotease pro-ADAMTS9 is influenced by the chaperone GRP94/gp96. The Journal of biological chemistry 37 19875450
2022 METTL3-Mediated ADAMTS9 Suppression Facilitates Angiogenesis and Carcinogenesis in Gastric Cancer. Frontiers in oncology 36 35574388
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
2020 Lnc RNA ZFAS1 regulates the proliferation, apoptosis, inflammatory response and autophagy of fibroblast-like synoviocytes via miR-2682-5p/ADAMTS9 axis in rheumatoid arthritis. Bioscience reports 33 32744323
2022 Long noncoding RNA ADAMTS9-AS1 represses ferroptosis of endometrial stromal cells by regulating the miR-6516-5p/GPX4 axis in endometriosis. Scientific reports 32 35173188
2012 PPARG2 Pro12Ala and ADAMTS9 rs4607103 as "insulin resistance loci" and "insulin secretion loci" in Italian individuals. The GENFIEV study and the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 4. Acta diabetologica 30 23161442
2018 MicroRNA-190b regulates lipid metabolism and insulin sensitivity by targeting IGF-1 and ADAMTS9 in non-alcoholic fatty liver disease. Journal of cellular biochemistry 29 29575055
2014 Perlecan antagonizes collagen IV and ADAMTS9/GON-1 in restricting the growth of presynaptic boutons. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 25080592
2020 Upregulation of TNF-α and IL-6 induces preterm premature rupture of membranes by activation of ADAMTS-9 in embryonic membrane cells. Life sciences 26 32781068
2021 DNMT3A-mediated silence in ADAMTS9 expression is restored by RNF180 to inhibit viability and motility in gastric cancer cells. Cell death & disease 25 33931579
2020 LncRNA ADAMTS9-AS2 suppresses the proliferation of gastric cancer cells and the tumorigenicity of cancer stem cells through regulating SPOP. Journal of cellular and molecular medicine 25 32160650
2019 ADAMTS9 Regulates Skeletal Muscle Insulin Sensitivity Through Extracellular Matrix Alterations. Diabetes 25 30626608
2019 ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in mouse model of Peters plus syndrome. Human molecular genetics 25 31600785
2017 The ADAMTS9 gene is associated with cognitive aging in the elderly in a Taiwanese population. PloS one 25 28225792
2021 ADAMTS9-AS1 Constrains Breast Cancer Cell Invasion and Proliferation via Sequestering miR-301b-3p. Frontiers in cell and developmental biology 24 34900984
2019 A disintegrin-like and metalloproteinase domain with thrombospondin type 1 motif 9 (ADAMTS9) regulates fibronectin fibrillogenesis and turnover. The Journal of biological chemistry 23 31085586
2019 Mechanical strain attenuates cytokine-induced ADAMTS9 expression via transient receptor potential vanilloid type 1. Experimental cell research 23 31415758
2017 ADAMTS9 is Silenced by Epigenetic Disruption in Colorectal Cancer and Inhibits Cell Growth and Metastasis by Regulating Akt/p53 Signaling. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 23 29186710
2012 Identification of a novel ADAMTS9/GON-1 function for protein transport from the ER to the Golgi. Molecular biology of the cell 22 22419820
2010 High-resolution melting analysis of ADAMTS9 methylation levels in gastric, colorectal, and pancreatic cancers. Cancer genetics and cytogenetics 22 19963134
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
2017 The 3p14.2 tumour suppressor ADAMTS9 is inactivated by promoter CpG methylation and inhibits tumour cell growth in breast cancer. Journal of cellular and molecular medicine 21 29193730
2015 A deletion at ADAMTS9-MAGI1 locus is associated with psoriatic arthritis risk. Annals of the rheumatic diseases 21 25990289
2020 LncRNA ADAMTS9-AS1 Restrains the Aggressive Traits of Breast Carcinoma Cells via Sponging miR-513a-5p. Cancer management and research 19 33149676
2023 Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9. Open medicine (Warsaw, Poland) 18 36941991
2023 N6-methyladenosine-mediated overexpression of long noncoding RNA ADAMTS9-AS2 triggers neuroblastoma differentiation via regulating LIN28B/let-7/MYCN signaling. JCI insight 18 37991019
2021 Long non-coding RNA ADAMTS9-AS1 inhibits the progression of prostate cancer by modulating the miR-142-5p/CCND1 axis. The journal of gene medicine 18 33704879
2021 Long non-coding RNA ADAMTS9-AS2 inhibits liver cancer cell proliferation, migration and invasion. Experimental and therapeutic medicine 18 33850531
2019 Adamts9 is necessary for ovarian development in zebrafish. General and comparative endocrinology 18 30951722
2018 Melanocyte development in the mouse tail epidermis requires the Adamts9 metalloproteinase. Pigment cell & melanoma research 18 29781574
2022 ADAMTS9-AS2 regulates PPP1R12B by adsorbing miR-196b-5p and affects cell cycle-related signaling pathways inhibiting the malignant process of esophageal cancer. Cell cycle (Georgetown, Tex.) 17 35503407
2020 Long non-coding RNA ADAMTS9-AS1 exacerbates cell proliferation, migration, and invasion via triggering of the PI3K/AKT/mTOR pathway in hepatocellular carcinoma cells. American journal of translational research 17 33042449
2022 ADAMTS9-AS2 Promotes Angiogenesis of Brain Microvascular Endothelial Cells Through Regulating miR-185-5p/IGFBP-2 Axis in Ischemic Stroke. Molecular neurobiology 16 35098480
2019 Upregulation of adamts9 by gonadotropin in preovulatory follicles of zebrafish. Molecular and cellular endocrinology 16 31586455
2019 ADAMTS-9 in Mouse Cartilage Has Aggrecanase Activity That Is Distinct from ADAMTS-4 and ADAMTS-5. International journal of molecular sciences 15 30699963
2009 ADAMTS-9 expression is up-regulated following transient middle cerebral artery occlusion (tMCAo) in the rat. Neuroscience letters 15 19348733
2021 The lncRNA ADAMTS9-AS2 Regulates RPL22 to Modulate TNBC Progression via Controlling the TGF-β Signaling Pathway. Frontiers in oncology 14 34178640
2017 MiR-338-5p suppresses rheumatoid arthritis synovial fibroblast proliferation and invasion by targeting ADAMTS-9. Clinical and experimental rheumatology 13 28850027
2023 LncRNA ADAMTS9-AS1 inhibits the stemness of lung adenocarcinoma cells by regulating miR-5009-3p/NPNT axis. Genomics 12 36870548
2023 The lncRNA ADAMTS9-AS1/miR-185-5p/KAT7 ceRNA network inhibits cardiomyocyte hypertrophy in hypertrophic obstructive cardiomyopathy. Biomedical research (Tokyo, Japan) 12 37258203
2022 Melittin inhibits the proliferation migration and invasion of HCC cells by regulating ADAMTS9-AS2 demethylation. Toxicon : official journal of the International Society on Toxinology 12 36535531
2020 Long Noncoding RNA ADAMTS9-AS2 Inhibits the Proliferation, Migration, and Invasion in Bladder Tumor Cells. OncoTargets and therapy 12 32801743
2023 Degradomic Identification of Membrane Type 1-Matrix Metalloproteinase as an ADAMTS9 and ADAMTS20 Substrate. Molecular & cellular proteomics : MCP 11 37169079
2017 Hemoglobin stimulates the expression of ADAMTS-5 and ADAMTS-9 by synovial cells: a possible cause of articular cartilage damage after intra-articular hemorrhage. BMC musculoskeletal disorders 11 29137610
2022 LncRNA ADAMTS9-AS1 knockdown suppresses cell proliferation and migration in glioma through downregulating Wnt/β-catenin signaling pathway. Bosnian journal of basic medical sciences 10 34923953
2022 lncRNA ADAMTS9-AS1/circFN1 Competitively Binds to miR-206 to Elevate the Expression of ACTB, Thus Inducing Hypertrophic Cardiomyopathy. Oxidative medicine and cellular longevity 10 35401927
2021 ADAMTS9-AS2: A Functional Long Non-coding RNA in Tumorigenesis. Current pharmaceutical design 10 33823762
2018 ADAMTS9, a member of the ADAMTS family, in Xenopus development. Gene expression patterns : GEP 10 29935379
2017 Adaptive sequence convergence of the tumor suppressor ADAMTS9 between small-bodied mammals displaying exceptional longevity. Aging 10 28244876
2013 Epigenetic inactivation of ADAMTS9 via promoter methylation in multiple myeloma. Molecular medicine reports 10 23358566
2023 A review on the role of ADAMTS9-AS2 in different disorders. Pathology, research and practice 9 36746036
2021 Delay in primordial germ cell migration in adamts9 knockout zebrafish. Scientific reports 9 33879810
2022 ADAMTS9-AS1 Long Non‑coding RNA Sponges miR‑128 and miR-150 to Regulate Ras/MAPK Signaling Pathway in Glioma. Cellular and molecular neurobiology 8 36449154
2021 Long-Chain Noncoding RNA ADAMTS9-AS2 Regulates Proliferation, Migration, and Apoptosis in Bladder Cancer Cells Through Regulating miR-182-5p. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 8 33621133
2021 The diagnostic significance of circulating lncRNA ADAMTS9-AS2 tumor biomarker in non-small cell lung cancer among the Egyptian population. The journal of gene medicine 8 34312940
2019 [Overexpression of the long non-coding RNA ADAMTS9-AS2 suppresses colorectal cancer proliferation and metastasis]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 8 31413211
2015 Loss of C. elegans GON-1, an ADAMTS9 Homolog, Decreases Secretion Resulting in Altered Lifespan and Dauer Formation. PloS one 8 26218657
2023 Disease modeling of ADAMTS9-related nephropathy using kidney organoids reveals its roles in tubular cells and podocytes. Frontiers in medicine 7 37035301
2016 Relationship between cytosine-adenine repeat polymorphism of ADAMTS9 gene and clinical and radiologic severity of knee osteoarthritis. International journal of rheumatic diseases 7 27230574
2021 LncRNA ADAMTS9-AS1 knockdown restricts cell proliferation and EMT in non-small cell lung cancer. Histology and histopathology 6 34085704
2016 Maternal serum ADAMTS-9 levels in gestational diabetes: a pilot study. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 6 27485821
2025 The lncRNAs PART1 and ADAMTS9-AS2 act in an antithetic manner on AR signaling and induction of cellular senescence in prostate cancer cells. International journal of surgery (London, England) 5 40143747
2020 The ADAMTS9 gene is associated with mandibular retrusion in a Chinese population. Gene 5 32335142

Missed literature

Know a paper Affinage missed for ADAMTS9? Flag it for the maintainers and the community.

No submissions yet.