Affinage

ADAM15

Disintegrin and metalloproteinase domain-containing protein 15 · UniProt Q13444

Length
863 aa
Mass
93.0 kDa
Annotated
2026-06-09
96 papers in source corpus 38 papers cited in narrative 38 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

ADAM15 is a furin-processed, membrane-anchored ADAM-family metalloprotease-disintegrin that bridges cell adhesion, ectodomain shedding, and intracellular signaling to control vascular, skeletal, cardiac, and inflammatory tissue homeostasis (PMID:9516430, PMID:12897135, PMID:25249606). Its prodomain is removed by a furin-like convertase in the trans-Golgi network, generating mature protein that is both surface-displayed and substantially retained in a perinuclear TGN/endosomal pool (PMID:9748307). The RGD-containing disintegrin domain directly engages integrins αvβ3 and α5β1 in a cation- and RGD-dependent manner, with flanking residues dictating receptor specificity, supporting cell adhesion at cell-cell contacts and modulating migration (PMID:9516430, PMID:9914169, PMID:11697891). The metalloprotease domain catalyzes ectodomain shedding of membrane substrates including E-cadherin, N-cadherin, FGFR2iiib, CD23, and TRIF and activates pro-MMP9; this activity requires the full-length membrane-anchored enzyme (soluble ADAM15 is inactive against peptide substrates) and is blocked by hydroxamate inhibitors and TIMP-3 but not by phorbol esters (PMID:12777399, PMID:18434311, PMID:18281484, PMID:19207106, PMID:23365087, PMID:26323669). Shed E-cadherin promotes HER2/HER3 heterodimerization and ERK signaling to drive tumor cell migration (PMID:18434311). The cytoplasmic tail functions as a phosphorylation-dependent scaffold that recruits Src-family kinases, Grb2, FAK, calmodulin, and PABP1, enabling protease-independent activation of Src/FAK/ERK/PI3K signaling, endothelial barrier regulation, apoptosis resistance, mechanotransduction, and local membrane-associated mRNA translation (PMID:11741929, PMID:20189953, PMID:22544741, PMID:30003689, PMID:30265671). Alternative splicing of the cytoplasmic domain selects distinct SH3-containing partners (Src, Brk, Nck, nephrocystin, SNX33) and tunes both catalytic activity and adhesion/invasion phenotypes in an isoform-specific manner (PMID:19487280, PMID:18296648, PMID:19718658). In vivo loss-of-function studies establish ADAM15 as required for pathological neovascularization, cartilage and bone homeostasis, post-infarction scar formation, and suppression of pressure-overload cardiac hypertrophy, with catalytic activity dispensable for its angiogenic role (PMID:12897135, PMID:15818704, PMID:25249606, PMID:34995785, PMID:36330793, PMID:21801086).

Mechanistic history

Synthesis pass · year-by-year structured walk · 38 steps
  1. 1998 High

    Established the molecular basis of ADAM15-integrin recognition, showing the disintegrin domain is a sequence-specific integrin ligand rather than a generic RGD motif.

    Evidence GST-fusion disintegrin domain binding to recombinant integrins with RGD and flanking-sequence mutagenesis

    PMID:9516430

    Open questions at the time
    • Did not test integrin binding in native membrane context
    • Functional consequence of αvβ3 binding not assessed here
  2. 1998 High

    Defined how ADAM15 zymogen is activated, identifying furin-mediated prodomain removal in the TGN and revealing a large intracellular pool.

    Evidence Pulse-chase, brefeldin A/monensin block, endoglycosidase H resistance, and in vitro furin cleavage in transfected COS-7 cells

    PMID:9748307

    Open questions at the time
    • Functional role of the intracellular pool unresolved
    • Whether processing gates catalytic activity not shown
  3. 1999 High

    Confirmed that ADAM15 mediates integrin-dependent cell adhesion on physiological cell types, extending in vitro binding to cellular function.

    Evidence Solid-phase cell-adhesion assays with Fc-fusion ectodomain, antibody blocking, and RGD competition

    PMID:9914169

    Open questions at the time
    • Did not address signaling downstream of adhesion
  4. 1999 High

    First implicated the cytoplasmic tail as a protein-interaction scaffold, linking ADAM15 to SH3-domain proteins in a maturation-state-dependent way.

    Evidence Yeast two-hybrid, GST pulldown, and co-IP identifying endophilin I and SH3PX1 binding the precursor form

    PMID:10531379

    Open questions at the time
    • Functional output of these interactions undefined
    • Precursor-specificity mechanism unexplained
  5. 2001 High

    Connected the cytoplasmic tail to tyrosine-kinase signaling, showing it is a phosphorylation-dependent docking site for Src-family kinases and Grb2.

    Evidence SH3 pulldown, co-IP, in vitro kinase assays, Far Western, and tyrosine/proline-motif mutagenesis in hematopoietic cells

    PMID:11741929

    Open questions at the time
    • Downstream signaling outputs not yet mapped
    • In vivo relevance unaddressed
  6. 2001 Medium

    Demonstrated a cellular adhesion phenotype, positioning ADAM15 at cell-cell contacts where it restrains migration and reinforces junctions.

    Evidence Regulated overexpression in NIH3T3, migration/permeability/adhesion assays, and junctional immunolocalization

    PMID:11697891

    Open questions at the time
    • No molecular pathway placement
    • Single overexpression system
  7. 2002 Medium

    Linked ADAM15 to endothelial junctions, showing VE-cadherin engagement drives its surface delivery.

    Evidence Immunofluorescence colocalization and VE-cadherin co-transfection with ADAM15-GFP in CHO cells

    PMID:12243749

    Open questions at the time
    • Mechanism of VE-cadherin-driven trafficking unknown
    • No loss-of-function validation
  8. 2003 Medium

    Provided the first substrate evidence for ADAM15 proteolysis with a specificity distinct from ADAM17.

    Evidence Synthetic peptide library screening with recombinant ADAM15 and cell-based CD23 shedding assays

    PMID:12777399

    Open questions at the time
    • Much mechanistic detail was for ADAM8, not ADAM15
    • Physical ADAM15-CD23 interaction not directly shown
  9. 2003 High

    First in vivo demonstration that ADAM15 is selectively required for pathological, not developmental, neovascularization.

    Evidence adam15−/− mice in oxygen-induced retinopathy and melanoma implantation models

    PMID:12897135

    Open questions at the time
    • Molecular mechanism of the angiogenic requirement undefined
    • Catalytic vs non-catalytic contribution not separated
  10. 2005 High

    Established a chondroprotective homeostatic role, linking ADAM15 to ECM adhesion and chondrocyte survival.

    Evidence ADAM15 overexpression in chondrocytes with collagen adhesion/viability assays and aging study of ADAM15−/− mice

    PMID:15818704

    Open questions at the time
    • Signaling pathway behind chondroprotection not yet identified
  11. 2008 High

    Identified a catalytic substrate (E-cadherin) whose shed fragment activates ErbB receptor signaling, defining a tumor-promoting proteolytic axis.

    Evidence Overexpression/knockdown, catalytic-dead mutant, inhibitor treatment, and sE-cad/HER2/HER3 co-IP in breast cancer cells

    PMID:18434311

    Open questions at the time
    • In vivo relevance of the sE-cad/ErbB axis not tested here
  12. 2008 High

    Defined a pro-metastatic role through N-cadherin shedding, MMP9 activity, and integrin/CD44 surface regulation.

    Evidence shRNA knockdown in PC-3 cells with multiple invasion/adhesion assays plus SCID bone-metastasis model

    PMID:18281484

    Open questions at the time
    • Direct catalytic cleavage of N-cadherin by ADAM15 not isolated from indirect effects
  13. 2008 High

    Showed alternative cytoplasmic splicing controls catalytic output via Src, establishing inside-out regulation of shedding.

    Evidence FGFR2iiib shedding compared across ADAM15A/B, Src inhibitors, and Src−/− rescue

    PMID:19487280

    Open questions at the time
    • How Src phosphorylation mechanistically activates the ectodomain remains unresolved
  14. 2008 Medium

    Mapped isoform-specific SH3 partner selection to opposing adhesion/invasion phenotypes between splice variants.

    Evidence Splice-variant cloning, GST-cytoplasmic-domain pulldowns, and functional assays in MDA-MB-435 cells

    PMID:18296648

    Open questions at the time
    • Single cell line
    • Direct binding not validated by reciprocal co-IP
  15. 2008 Medium

    Extended ADAM15 function to reproduction, implicating its disintegrin domain in sperm-egg adhesion and fusion.

    Evidence Western blot of sperm processing and disintegrin-peptide inhibition of sperm-oolemma binding

    PMID:18390692

    Open questions at the time
    • Receptor partner on the oolemma not identified
    • Peptide inhibition is indirect evidence
  16. 2009 High

    Clarified that membrane anchoring is essential for catalysis and defined the inhibitor/TIMP profile distinguishing ADAM15 from other sheddases.

    Evidence Negative peptide reconstitution plus cell-based FGFR2iiib shedding with E→A mutant, hydroxamates, and TIMP titration

    PMID:19207106

    Open questions at the time
    • Structural basis for membrane-dependence of activity unknown
  17. 2009 Medium

    Showed alternative exon usage selects distinct intracellular partners (nephrocystin, SNX33) through specific proline motifs.

    Evidence Co-precipitation and proline-motif mutagenesis across ADAM15 isoforms

    PMID:19718658

    Open questions at the time
    • Functional consequences of nephrocystin/SNX33 recruitment untested
  18. 2009 Medium

    Linked ADAM15 to outside-in chondrocyte signaling, assigning prodomain and cytoplasmic-tail roles in FAK activation.

    Evidence ADAM15 deletion mutants in chondrocytes with phospho-FAK Western blot and FAK co-IP

    PMID:18774960

    Open questions at the time
    • Whether ADAM15-FAK binding is direct not resolved here
  19. 2010 High

    Demonstrated a protease-independent endothelial barrier function driven by the cytoplasmic tail through Src/ERK.

    Evidence Wild-type and catalytic-dead ADAM15 in HUVECs, permeability/TEER/transmigration assays, and Src/ERK inhibitors

    PMID:20189953

    Open questions at the time
    • Upstream trigger of ADAM15-driven Src/ERK activation in endothelium unclear
  20. 2010 Medium

    Identified GRP78 as the receptor for an ADAM15-derived angiogenic peptide acting via Akt/ERK independent of VEGFR-2.

    Evidence Synthetic HWRR peptide, GRP78 siRNA epistasis, and hind-limb ischemia model

    PMID:20145413

    Open questions at the time
    • Whether full-length ADAM15 generates this peptide physiologically is unknown
  21. 2010 Medium

    Defined an anti-apoptotic mechanism via cytoplasmic-tail-dependent XIAP upregulation in chondrocytes.

    Evidence Full-length vs tail-deleted ADAM15 transfection, ADAM15/XIAP siRNA, and caspase 3/7 assays

    PMID:20213810

    Open questions at the time
    • Signaling link between ADAM15 tail and XIAP transcription unmapped
  22. 2011 Medium

    Revealed that ADAM15 restrains osteoblast activation by suppressing Wnt/β-catenin signaling, defining a skeletal homeostatic role.

    Evidence ADAM15−/− mouse bone histomorphometry and osteoblast assays with β-catenin/cyclin D1/c-Jun readouts

    PMID:21801086

    Open questions at the time
    • Mechanism by which ADAM15 modulates β-catenin stability unidentified
  23. 2012 High

    Identified FAK as the direct adaptor coupling the ADAM15 tail to Src activation under genotoxic stress.

    Evidence Mammalian two-hybrid, GST pulldown, Far Western, and IL-2Rα-ADAM15 chimeric activation construct

    PMID:22544741

    Open questions at the time
    • Stimulus-specificity of the ADAM15-FAK-Src axis beyond genotoxic stress not defined
  24. 2012 Medium

    Showed ADAM15 is exported as exosomal cargo that acts as a soluble αvβ3 ligand suppressing adhesion and tumor growth.

    Evidence Exosome isolation, PKC-stimulated release, RGD-dependent binding, and in vivo tumor assays

    PMID:22505472

    Open questions at the time
    • Mechanism sorting ADAM15 into exosomes unknown
  25. 2013 Medium

    Placed ADAM15 as a negative regulator of innate immune TRIF signaling and a TRIF interactor/substrate.

    Evidence TRIF complex co-IP/LC-MS/MS, NF-κB/IFN-β reporters, and ADAM15 siRNA cytokine assays

    PMID:23365087

    Open questions at the time
    • TRIF cleavage reported but not biochemically dissected
    • Single lab
  26. 2013 Medium

    Extended ADAM15-FAK/Src signaling to apoptosis resistance in rheumatoid synovial fibroblasts via PI3K/NF-κB.

    Evidence siRNA knockdown in RASFs with caspase assays and FAK/Src inhibitors

    PMID:23918525

    Open questions at the time
    • Direct receptor input to the ADAM15 complex not defined here
  27. 2014 Medium

    Identified acrogranin as a surface partner of ADAM15 functionally implicated in sperm-egg adhesion.

    Evidence Co-IP, N-terminal sequencing, and anti-acrogranin inhibition of fertilization

    PMID:25392190

    Open questions at the time
    • Functional consequence of the ADAM15-acrogranin complex in cancer cells untested
  28. 2015 Medium

    Established ADAM15 as both a transcriptional inducer and direct activator of pro-MMP9, promoting invasion.

    Evidence Knockdown/overexpression, ADAM15-MMP9 co-IP, in vitro pro-MMP9 cleavage, and MMP9 rescue in lung cancer cells

    PMID:26323669

    Open questions at the time
    • Relative contribution of transcriptional vs proteolytic MMP9 activation unresolved
  29. 2014 High

    Genetically separated catalytic from non-catalytic functions in vivo, showing protease activity is dispensable for pathological retinal neovascularization.

    Evidence Adam15 E→A knock-in mice in oxygen-induced retinopathy and tumor models

    PMID:25249606

    Open questions at the time
    • Which non-catalytic activity drives neovascularization not pinpointed
  30. 2018 High

    Defined a Ca2+/calmodulin-gated assembly of the ADAM15/Fas/Src/FAK survival complex in synovial fibroblasts.

    Evidence CaM pulldown, recombinant CaM binding, CRAC/CaM inhibitors, and tail-deletion mutant with caspase assays

    PMID:30003689

    Open questions at the time
    • Stoichiometry and order of complex assembly not fully resolved
  31. 2018 Medium

    Uncovered a novel role coupling adhesion to local translation through transient PABP1 recruitment to membrane foci.

    Evidence ADAM15-PABP1 co-IP, GST domain mapping, puromycin labeling of nascent proteins, and tail-deletion mutant

    PMID:30265671

    Open questions at the time
    • Identity of locally translated mRNAs unknown
    • Single lab
  32. 2019 Medium

    Showed catalytic and isoform-specific ADAM15 regulates tight-junction Claudin-1 via PI3K/Akt/mTOR and ZO1/ZO2 association.

    Evidence Isogenic ADAM15 wild-type/catalytic-dead isoform panels, co-IP, and pathway inhibitors in breast cancer cells

    PMID:31467400

    Open questions at the time
    • Direct catalytic substrate driving Claudin-1 induction not identified
  33. 2019 Medium

    Identified shear stress/KLF2 as a transcriptional driver of ADAM15 supporting flow-dependent endothelial survival.

    Evidence Flow culture, KLF2 overexpression/siRNA, promoter analysis, and ADAM15 shRNA survival assays

    PMID:31271758

    Open questions at the time
    • Downstream survival effector under flow not defined
  34. 2021 Medium

    Defined ADAM15 as a mechanotransduction hub regulating TRPV4 surface density and pannexin-1/ATP purinergic signaling.

    Evidence ADAM15 siRNA in synovial fibroblasts with mechanical stimulation and multiple channel/signaling readouts

    PMID:34685689

    Open questions at the time
    • Mechanism by which ADAM15 controls TRPV4 trafficking unknown
  35. 2022 Medium

    Established ADAM15 as required for organized post-infarction collagen cross-linking and scar integrity via PAK1/LOX-1/fibronectin.

    Evidence Adam15−/− mice after LAD ligation with collagen imaging, solubility fractionation, and effector Western blots

    PMID:34995785

    Open questions at the time
    • Whether ADAM15 acts catalytically or as scaffold in fibroblast activation unresolved
  36. 2022 Medium

    Showed ADAM15 suppresses pressure-overload cardiac hypertrophy through integrin-α7/laminin and calcineurin/NFAT control.

    Evidence Adam15−/− TAC mice, calcineurin activity assays, cyclosporin-A rescue, and cardiomyocyte stretch assay

    PMID:36330793

    Open questions at the time
    • Direct molecular link between ADAM15 and integrin-α7 regulation unclear
  37. 2025 Medium

    Assigned ADAM15 a selective role in death-receptor necroptosis and TNF-R1 trafficking, distinct from apoptosis control.

    Evidence CRISPR knockout in U937/Jurkat, multiple death ligands, caspase-8/RIPK1 analysis, and TNF-R1 surface flow cytometry

    PMID:41340056

    Open questions at the time
    • TNF-R1 proposed but not confirmed as a catalytic substrate
    • Mechanism of necroptosis regulation undefined
  38. 2025 Medium

    Defined a strain-induced ADAM15/N-cadherin/PAK2/Nck mechanosignaling complex driving invasive gene expression in synovial fibroblasts.

    Evidence ADAM15 knockdown in RASFs, complex co-IP, phospho-PAK2 blots, and lncRNA/miRNA/CDH11 readouts

    PMID:40118917

    Open questions at the time
    • Whether ADAM15 catalytic activity contributes to this complex untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ADAM15 isoform-specific cytoplasmic scaffolding, catalytic shedding, and integrin adhesion are integrated and prioritized within a single cell, and which functions dominate in each tissue context, remains unresolved.
  • No structural model of the full-length protein in its membrane context
  • Endogenous substrate repertoire incompletely defined
  • Relative in vivo contribution of catalytic vs scaffold activity unresolved across tissues

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0008092 cytoskeletal protein binding 3 GO:0016787 hydrolase activity 3 GO:0060090 molecular adaptor activity 3 GO:0098631 cell adhesion mediator activity 3
Localization
GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 2 GO:0005764 lysosome 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-5357801 Programmed Cell Death 5 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-168256 Immune System 2
Partners
CALM1GRB2ITGAVITGB1ITGB3PABPC1PTK2SRC

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 The recombinant disintegrin-like domain of ADAM15 (MDC-15) specifically binds integrin αvβ3 in an RGD-dependent manner; mutation of RGD to SGA completely blocks binding, and mutation of the flanking sequence RPTRGD to NWKRGD extends specificity to include αIIbβ3, demonstrating that the flanking sequence determines receptor binding specificity. GST fusion protein binding assay with recombinant integrins, site-directed mutagenesis The Journal of biological chemistry High 9516430
1999 The extracellular domain of ADAM15 (metargidin) mediates cell adhesion to haemopoietic cell lines via αvβ3 (on U937 monocytic cells) and α5β1 (on MOLT-4 T cells) integrins; adhesion is divalent cation-dependent, Mn2+-enhanced, and inhibited by RGD-based peptides, consistent with integrin-mediated binding through the disintegrin domain. Solid-phase cell-adhesion assay using Fc-fusion extracellular domain, blocking antibodies, RGD peptide competition, purified recombinant integrins Journal of cell science High 9914169
1998 Mouse MDC15 (ADAM15) is processed by a furin-like pro-protein convertase in a late Golgi/trans-Golgi network compartment: brefeldin A and monensin block pro-domain removal, mature protein is endoglycosidase H-resistant, and recombinant furin cleaves mMDC15 in vitro. More than half of mature mMDC15 is intracellular, accumulating in a perinuclear region resembling the TGN/endosomal compartments. Pulse-chase experiments in transfected COS-7 cells, brefeldin A/monensin treatment, endoglycosidase H resistance assay, in vitro furin cleavage, cell-surface trypsinization, immunolocalization The Journal of biological chemistry High 9748307
1999 The cytoplasmic domains of MDC15 (ADAM15) and MDC9 interact with two SH3 domain-containing proteins, endophilin I (SH3GL2) and SH3PX1; both preferentially bind the precursor (not processed) form of ADAM15. Interactions were validated by yeast two-hybrid, bacterial fusion protein pulldown, and co-immunoprecipitation from COS-7 cells. Yeast two-hybrid screen, bacterial GST-fusion pulldown, co-immunoprecipitation from COS-7 cells The Journal of biological chemistry High 10531379
2001 The cytoplasmic domain of ADAM15 interacts with multiple Src family kinases (Lck, Fyn, Abl, Src, Hck) via their SH3 domains, and with adaptor Grb2; interactions are phosphorylation-dependent. Hck and Lck phosphorylate the ADAM15 cytoplasmic domain in vitro; PMA stimulation increases ADAM15 phosphorylation in Jurkat cells. Tyr715 and Tyr735 and proline-rich motifs are required for binding, established by deletion and point mutants. SH3-domain pulldown, co-immunoprecipitation from hematopoietic cells, in vitro kinase assay (immune complex), Far Western, dephosphorylation assay, deletion/point mutagenesis, PMA stimulation The Journal of biological chemistry High 11741929
2001 Overexpression of ADAM15 in NIH3T3 cells decreases cell migration on fibronectin, reduces monolayer permeability, and increases cell-cell adhesion (~45% increase). ADAM15 localizes to cell-cell contacts in an epithelial cell line, suggesting it functions as an adhesion molecule at cell-cell contact structures. Tetracycline-regulated overexpression, Boyden chamber migration assay, scratch wound assay, permeability assay, retroviral transduction, cell adhesion assay, immunolocalization Experimental cell research Medium 11697891
2002 ADAM15 co-localizes with VE-cadherin at endothelial cell adherens junctions; VE-cadherin-mediated adherens junction formation drives cell-surface expression of ADAM15. Co-expression of VE-cadherin with ADAM15-GFP in CHO cells causes translocation of ADAM15 to the cell periphery and increases surface ADAM15 levels. Immunofluorescence colocalization, ADAM15-GFP fusion protein live imaging, VE-cadherin co-transfection, flow cytometry for surface ADAM15 Experimental cell research Medium 12243749
2003 ADAM15 catalyzes ectodomain shedding of CD23 (low affinity IgE receptor) in cell-based assays, similar to ADAM8 and ADAM28; ADAM8-dependent CD23 release requires proteolytically active enzyme and is associated with physical interaction of ADAM8 with membrane CD23. Screening of synthetic peptide substrates showed that ADAM15 has proteolytic substrate specificity distinct from ADAM17. Synthetic peptide substrate library screening with recombinant soluble ADAM15, cell-based CD23 ectodomain shedding assay, metalloprotease inhibitor blocking The Journal of biological chemistry Medium 12777399
2003 ADAM15 knock-out (adam15−/−) mice show a major reduction in pathological retinal neovascularization in an oxygen-induced retinopathy model and significantly smaller tumors from implanted B16F0 melanoma cells compared to wild-type controls, demonstrating ADAM15 is required for pathological neovascularization but not developmental angiogenesis. Targeted gene deletion (adam15−/− mice), oxygen-induced retinopathy model, subcutaneous melanoma implantation model Molecular and cellular biology High 12897135
2005 ADAM15 overexpression in chondrocytes (T/C28a4 cell line) specifically reinforces adhesion to type II and VI collagen (but not fibronectin) and enhances cell viability under serum starvation. ADAM15−/− mice develop accelerated osteoarthritic lesions compared to wild-type, demonstrating a homeostatic/chondroprotective role in cartilage. Stable transfection of T/C28a4 chondrocytes with full-length ADAM15 cDNA, adhesion assays on ECM proteins, cell viability assay, ADAM15−/− mouse aging study with histological analysis Arthritis and rheumatism High 15818704
2008 ADAM15 cleaves E-cadherin ectodomain in response to growth factor deprivation in breast cancer cells; cleavage is abrogated by metalloproteinase inhibitor and by catalytically inactive ADAM15 mutant. The shed soluble E-cadherin fragment forms a complex with HER2 and HER3 receptors, stabilizes HER2/HER3 heterodimerization, and activates Erk signaling to support cell migration and proliferation. ADAM15 overexpression and shRNA knockdown in breast cancer cells, catalytically inactive ADAM15 mutant, metalloproteinase inhibitor treatment, co-immunoprecipitation of sE-cad with HER2/HER3, Erk phosphorylation assay, migration/proliferation assays The Journal of biological chemistry High 18434311
2008 ADAM15 knockdown in metastatic prostate cancer PC-3 cells reduces N-cadherin cleavage at the cell surface, decreases cell migration and adhesion to extracellular matrix proteins, reduces cell surface αv integrin and CD44, abrogates MMP9 secretion/activity, and reduces adhesion to and migration through vascular endothelial monolayers. In SCID mice, ADAM15 loss significantly attenuates bone metastasis. Lentiviral shRNA knockdown, N-cadherin shedding assay, FACS, Matrigel invasion, MMP9 zymography, in vitro vascular invasion assay, SCID mouse bone metastasis model Cancer research High 18281484
2008 An ADAM15 splice variant (ADAM15B) containing a cytoplasmic Src-binding site has enhanced catalytic activity (FGFR2iiib shedding) compared with ADAM15A (lacking Src-binding site); enhanced activity of ADAM15B is abolished by Src-kinase inhibitors and in Src−/− cells but restored by re-introduction of Src, establishing that Src-dependent phosphorylation of the cytoplasmic domain activates ADAM15B ectodomain shedding. Cell-based FGFR2iiib shedding assay, Src kinase inhibitors, Src−/− fibroblasts with and without Src rescue, comparison of ADAM15A vs ADAM15B splice variants Cancer research High 19487280
2008 ADAM15 splice variants (A, B, C) differ in isoform-specific interactions with Nck, Src, and Brk tyrosine kinases via their cytoplasmic domains (GST pulldown), while all interact equivalently with Grb2, Tks5/Fish, and ERK. Functionally, ADAM15A enhances adhesion, migration, and invasion whereas ADAM15B reduces adhesion in MDA-MB-435 cells. RT-PCR cloning of splice variants, GST-cytoplasmic domain pulldown assays, stable transfection of MDA-MB-435 cells, migration/invasion/adhesion assays Molecular cancer research : MCR Medium 18296648
2009 Soluble recombinant ADAM15 fails to cleave any tested synthetic peptide substrates. In cell-based assays, full-length membrane-anchored ADAM15 (but not catalytically inactive ADAM15 E→A mutant) increases shedding of FGFR2iiib; this activity is inhibited by hydroxamate metalloproteinase inhibitors (marimastat, TAPI-2, GM6001) and 50 nM TIMP-3, but not TIMP-1 or TIMP-2. ADAM15 is not stimulated by PMA or calcium ionophores. Peptide substrate library screening with purified soluble ADAM15, cell-based FGFR2iiib shedding assay, catalytic mutant (E→A), pharmacological inhibitors, TIMP titration The Biochemical journal High 19207106
2009 ADAM15 alternative splicing generates isoforms with distinct SH3-binding profiles; isoforms i4, i5, i6 (containing exons 20/21 proline-rich regions) strongly co-precipitate nephrocystin from cell lysates via RxLPxxP motifs, while robust association with SNX33 is specific to isoforms containing the C-terminal proline cluster. Alternative exon use thus regulates selection of intracellular binding partners. Co-precipitation from cell lysates, mutagenesis of proline motifs, RT-PCR characterization of isoforms Journal of cellular biochemistry Medium 19718658
2009 ADAM15 modulates outside-in signaling during chondrocyte-matrix interactions: the prodomain of ADAM15 is critical for enhancing type II collagen adhesion, and the cytoplasmic tail modulates FAK autophosphorylation at Y397 during chondrocyte-collagen interaction. ADAM15 cytoplasmic domain co-immunoprecipitates with FAK in this context. Stable transfection of T/C28a4 chondrocytes with ADAM15 deletion mutants, CII adhesion assay, Western blot for phospho-FAK, co-immunoprecipitation Journal of cellular and molecular medicine Medium 18774960
2010 ADAM15 regulates endothelial permeability and neutrophil transendothelial migration via Src/ERK1/2 signaling: both wild-type and catalytically dead ADAM15 increase basal and thrombin-induced permeability, showing the effect is protease-independent. ADAM15 overexpression promotes ERK1/2 phosphorylation; pharmacological inhibition of Src or ERK reverses ADAM15-induced hyperpermeability. ADAM15 does not cleave VE-cadherin. siRNA knockdown and overexpression (wild-type and catalytic mutant) in HUVECs, albumin transendothelial flux, TEER measurement, ERK1/2 phosphorylation Western blot, neutrophil transmigration assay, Src/ERK inhibitors Cardiovascular research High 20189953
2010 An ADAM15-derived peptide containing the HWRR sequence activates GRP78 on endothelial cell membranes, inducing angiogenesis via Akt phosphorylation and ERK1/2 activation independently of VEGFR-2; siRNA knockdown of GRP78 blocks peptide-induced angiogenesis, identifying GRP78 as the receptor for this ADAM15 domain-derived peptide. Synthetic peptide assay, cell proliferation/migration/tube formation assays, siRNA knockdown of GRP78, Akt/ERK phosphorylation Western blot, mouse hind limb ischemia model Journal of vascular research Medium 20145413
2010 ADAM15 exerts an anti-apoptotic effect in osteoarthritic chondrocytes by upregulating XIAP (~3-fold at protein and mRNA levels) upon genotoxic stress; siRNA knockdown of ADAM15 or XIAP sensitizes OA chondrocytes to camptothecin-induced caspase 3/7 activation. ADAM15 lacking its cytoplasmic tail loses anti-apoptotic activity. Stable ADAM15 transfection (full-length and cytoplasmic tail deletion) in T/C28a4 chondrocytes, siRNA knockdown, caspase 3/7 activity assay, ATP viability assay, Western blot, RT-PCR for XIAP, annexin V Arthritis and rheumatism Medium 20213810
2012 ADAM15 cytoplasmic domain directly binds the C-terminus of FAK (demonstrated by mammalian two-hybrid, GST pulldown, and Far Western assays); genotoxic stress triggers enhanced FAK phosphorylation at Y397, Y576, and Y861 plus Src Y416 activation in cells with full-length ADAM15 but not in cells expressing ADAM15 lacking the cytoplasmic tail. Src binds FAK but not ADAM15 directly, identifying FAK as the critical intracellular adaptor for ADAM15-dependent Src/FAK activation. Mammalian two-hybrid, GST pulldown, Far Western, Western blot for phospho-FAK/Src, chimeric IL-2Rα-ADAM15 cytoplasmic domain construct stimulated with IL-2, FAK/Src pharmacological inhibitors The Journal of biological chemistry High 22544741
2012 ADAM15 is released as an exosomal component from various cell types including human macrophages; PMA (a PKC activator) stimulates ADAM15 exosome release with a corresponding decrease in plasma membrane ADAM15. Exosomal ADAM15 binds integrin αvβ3 in an RGD-dependent manner and suppresses vitronectin/fibronectin-induced cell adhesion, growth, migration, and in vivo tumor growth. Exosome isolation and characterization, PMA stimulation, RGD-dependent binding assay to αvβ3, cell adhesion/migration/growth assays, in vivo tumor growth assay FASEB journal Medium 22505472
2013 ADAM15 was identified as a TRIF-interacting partner by immunoprecipitation of the TRIF signaling complex followed by LC-MS/MS; ADAM15 negatively regulates TRIF-mediated NF-κB and IFN-β signaling. ADAM15 mediates proteolytic cleavage of TRIF; suppression of ADAM15 enhances LPS/poly(I:C)-mediated proinflammatory cytokine production and viral-induced cytokines. Co-immunoprecipitation of TRIF complex + LC-MS/MS protein ID, NF-κB and IFN-β reporter assays, ADAM15 siRNA knockdown, cytokine measurements Journal of immunology Medium 23365087
2013 In rheumatoid arthritis synovial fibroblasts (RASFs), ADAM15 contributes to apoptosis resistance upon FasL stimulation by activating the FAK/Src/PI3K/NF-κB pathway; siRNA knockdown of ADAM15 increases caspase 3/7 activity after FasL or camptothecin exposure. FAK and Src inhibitors (FAK inhibitor 14, dasatinib) induce apoptosis potentiated by ADAM15 silencing. siRNA knockdown in RASFs, caspase 3/7 assay, annexin V staining, Western blot for phospho-FAK/Src/NF-κB, pharmacological inhibitors of FAK/Src Arthritis and rheumatism Medium 23918525
2015 ADAM15 upregulates MMP9 expression in lung cancer cells via activation of the MEK-ERK pathway; ADAM15 also proteolytically cleaves and activates pro-MMP9 in vitro, and interacts with MMP9 in vivo (co-immunoprecipitation). MMP9 knockdown attenuates ADAM15-overexpression-induced cell invasion. shRNA knockdown and overexpression, co-immunoprecipitation (ADAM15-MMP9 interaction), in vitro pro-MMP9 cleavage assay, MEK-ERK pathway analysis, Matrigel invasion assay, MMP9 siRNA rescue Oncology reports Medium 26323669
2014 The catalytic activity of ADAM15 (E→A knock-in mice) is NOT required for its role in promoting pathological neovascularization in the oxygen-induced retinopathy model; Adam15E>A mice show similar neovascularization to wild-type. However, tumor implantation was reduced in Adam15E>A mice. Cell-based assays show ADAM15 can process FGFR2iiib but not several angiogenesis-relevant receptors tested. Knock-in mice with inactivating E→A point mutation in catalytic site, oxygen-induced retinopathy model, heterotopic tumor model, cell-based receptor shedding assays Investigative ophthalmology & visual science High 25249606
2018 In RASFs, FasL-induced death signals trigger CRAC/Orai1 channel-dependent Ca2+ release, which drives CaM recruitment to both Fas/CD95 and ADAM15 at the cell membrane; Src associated with CaM becomes engaged in the ADAM15 complex also containing FAK, leading to Src/FAK phosphorylation and cell survival. ADAM15 cytoplasmic domain directly binds recombinant CaM (protein binding assay). An ADAM15 construct lacking the cytoplasmic domain loses anti-apoptotic activity. CaM-Sepharose pulldown, co-immunoprecipitation (ADAM15/Fas/CaM/Src/FAK), recombinant CaM binding assay, CaM inhibitor (trifluoperazine), CRAC/Orai1 inhibitor (BTP-2), ADAM15 tail-deletion mutant, caspase 3/7 assay, annexin V staining, siRNA, immunofluorescence colocalization Arthritis & rheumatology High 30003689
2018 Upon cell adhesion, the cytoplasmic domain of ADAM15 transiently binds poly(A) binding protein 1 (PABP1) via the PABP proline-rich linker; ADAM15 recruits PABP to cell membrane foci coinciding with active mRNA translation (detected by puromycin-terminated polypeptides). Loss of ADAM15 by siRNA or use of a cytoplasmic-tail-deleted ADAM15 mutant reduces cell membrane-associated neosynthesis of proteins during induced adhesion. Co-immunoprecipitation (ADAM15-PABP1), GST-domain mapping of PABP proline-rich linker, immunostaining with puromycin-labeling of nascent proteins, siRNA knockdown, ADAM15 cytoplasmic tail deletion mutant PloS one Medium 30265671
2019 ADAM15 mediates upregulation of Claudin-1 in breast cancer cells in a catalytic-function-dependent and isoform-specific manner (ADAM15A > C and E >> B); ADAM15A co-localizes with Claudin-1 and ZO1 at cell-cell junctions; ADAM15 co-immunoprecipitates with ZO1 and ZO2. The PI3K/Akt/mTOR pathway is involved in Claudin-1 regulation downstream of ADAM15. Isogenic cell panels expressing ADAM15 wild-type and catalytically inactive isoforms (MDA-MB-231 and MCF-7), shRNA knockdown, Western blot, immunofluorescence, co-immunoprecipitation of ADAM15/ZO1/ZO2, PI3K/Akt/mTOR inhibitors Scientific reports Medium 31467400
2019 Physiologic shear stress induces ADAM15 expression in endothelial cells (~4-fold mRNA, ~5.6-fold protein) through KLF2-dependent transcription; KLF2 overexpression increases ADAM15 expression and KLF2 siRNA prevents shear-induced ADAM15 upregulation. ADAM15 promotes endothelial survival under growth factor deprivation or TNF stimulation; shRNA knockdown of ADAM15 reduces survival specifically under flow conditions. Flow culture system, KLF2 overexpression and siRNA knockdown, promoter analysis (KLF2 consensus sites), simvastatin/geranylgeranyl pyrophosphate treatment, ADAM15 shRNA knockdown, cell viability assays under static and flow conditions Journal of molecular and cellular cardiology Medium 31271758
2021 ADAM15 promotes TRPV4 channel membrane density in synovial fibroblasts, thereby facilitating Ca2+-dependent JNK activation, HOTAIR lncRNA downregulation, and sirtuin-1 upregulation in response to mechanical stimuli. ADAM15 also reinforces Src-mediated pannexin-1 channel activation for ATP release (purinergic signaling); loss of ADAM15 completely abrogates this mechanosignaling pathway. ADAM15 siRNA knockdown in synovial fibroblasts, mechanical stimulation assay, TRPV4 surface expression quantification, JNK phosphorylation Western blot, HOTAIR lncRNA quantification, sirtuin-1 measurement, pannexin-1 channel assay, ATP release measurement Cells Medium 34685689
2022 ADAM15 is required for optimal collagen cross-linking and scar formation after myocardial infarction: Adam15−/− mice show markedly higher rates of left ventricular rupture (66% vs 15%), disorganized fibrillar collagen, reduced lysyl oxidase-1 (LOX-1) and fibronectin, and lower insoluble/higher soluble collagen fraction. ADAM15 deficiency is associated with reduced PAK1 levels (a regulator of fibronectin and LOX-1 expression). In vitro, Adam15−/− cardiac fibroblasts show suppressed activation under ischemia. Adam15−/− mice subjected to LAD ligation, echocardiography, second harmonic generation imaging of fibrillar collagen, Western blot for LOX-1/fibronectin/PAK1, collagen solubility fractionation, primary cardiac fibroblast hypoxia assay Matrix biology Medium 34995785
2022 Loss of ADAM15 worsens pressure-overload-induced eccentric hypertrophy and dilation in male mice via the calcineurin/NFAT pathway; Adam15−/− TAC mice show increased integrin-α7 expression with decreased integrin-laminin interaction and greater calcineurin activity; calcineurin inhibition (cyclosporin-A) blocks the excess hypertrophy in Adam15−/− mice. ADAM15 knockdown in vitro increases cardiomyocyte hypertrophy in response to mechanical stretch. Adam15−/− mice with transverse aortic constriction, echocardiography, calcineurin activity assay, NFAT phosphorylation, integrin-α7/β1/laminin Western blot and co-precipitation, cyclosporin-A pharmacological rescue, cardiomyocyte stretch assay, proteome profiling Hypertension Medium 36330793
2025 Loss of ADAM15 abrogates necroptosis (but not apoptosis or NF-κB/MAPK survival signaling) induced by TNF, TRAIL, FasL, TL1a, and Obatoclax in U937 and Jurkat cells; ADAM15-deficient cells show enhanced basal Caspase-8 activity and partial RIPK1 proteolysis. ADAM15 is found in intracellular compartments with lysosomal protein signatures, and TNF-R1 surface expression is enhanced in ADAM15-KO cells, suggesting TNF-R1 as a possible ADAM15 substrate involved in regulating receptor trafficking. CRISPR/Cas9 knockout, Western blot, flow cytometry for TNF-R1 surface expression, caspase-8 enzyme assay, RIPK1 Western blot, death ligand treatment (TNF/TRAIL/FasL/TL1a), bottom-up proteome analysis, immunomagnetic fractionation, microscopy for subcellular localization Cell communication and signaling Medium 41340056
2008 Mouse ADAM15 is present and post-translationally processed during epididymal sperm maturation and the acrosome reaction; Western blotting reveals proteolytic processing from 110/75 kDa forms to a 35 kDa form containing the disintegrin domain. A peptide from the ADAM15 disintegrin domain (RPPTDDCDLPEF) partially inhibits sperm-oolemma fusion and almost completely inhibits sperm-oolemma adhesion. Western blot of sperm at different epididymal segments, indirect immunofluorescence, disintegrin domain peptide inhibition assay of sperm-egg binding Reproduction (Cambridge, England) Medium 18390692
2014 ADAM15 forms a complex with acrogranin on the surface of guinea pig spermatozoa; co-immunoprecipitation identified a 65 kDa protein co-precipitating with ADAM15 and N-terminal sequencing revealed it as acrogranin. Anti-acrogranin antibody inhibits sperm-egg adhesion. ADAM15 and acrogranin are also associated in two breast cancer cell lines. Co-immunoprecipitation, N-terminal protein sequencing, cell-surface labeling, heterologous fertilization inhibition assay with anti-acrogranin antibody Reproduction (Cambridge, England) Medium 25392190
2011 Adam15−/− mice have increased bone volume and thickness with increased osteoblast number and activity; ADAM15−/− osteoblasts show increased proliferation, ALP activity, mineralization, and nuclear β-catenin accumulation (with increased membrane/cytoplasmic β-catenin degradation). Downstream β-catenin targets cyclin D1 and c-Jun are upregulated in ADAM15-null osteoblasts, indicating ADAM15 normally suppresses Wnt/β-catenin-driven osteoblast activation. Adam15−/− mouse bone histomorphometry, osteoblast primary culture assays (proliferation, ALP, nodule mineralization), β-catenin immunolocalization (nuclear vs. membrane/cytoplasm), Western blot for cyclin D1 and c-Jun Biological chemistry Medium 21801086
2025 In RASFs, mechanical strain triggers co-localization of ADAM15 with N-cadherin in adherens junctions and activates PAK2 phosphorylation; PAK2 and adaptor Nck are co-recruited to the NCAD/ADAM15 complex at the membrane. This leads to downregulation of lncRNA H19 and miR-130a-3p, and upregulation of cadherin-11 (CDH11), enhancing cell invasive properties. Disruption of ADAM15 abrogates the mechanosignaling response. ADAM15 siRNA/knockdown in RASFs, mechanical strain application, co-immunoprecipitation (ADAM15/NCAD/PAK2/Nck complex), Western blot for phospho-PAK2, RT-qPCR for H19/miR-130a-3p/CDH11, immunofluorescence colocalization, invasion assay Scientific reports Medium 40118917

Source papers

Stage 0 corpus · 96 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Specific interaction of the recombinant disintegrin-like domain of MDC-15 (metargidin, ADAM-15) with integrin alphavbeta3. The Journal of biological chemistry 196 9516430
1999 Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on different haemopoietic cells. Journal of cell science 177 9914169
2008 The ectodomain shedding of E-cadherin by ADAM15 supports ErbB receptor activation. The Journal of biological chemistry 163 18434311
2003 Potential role for ADAM15 in pathological neovascularization in mice. Molecular and cellular biology 155 12897135
2003 Catalytic activity of ADAM8, ADAM15, and MDC-L (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23. The Journal of biological chemistry 149 12777399
1999 Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1. The Journal of biological chemistry 149 10531379
2005 The disintegrin-metalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer. International journal of oncology 147 15586220
1998 Intracellular maturation of the mouse metalloprotease disintegrin MDC15. The Journal of biological chemistry 137 9748307
2001 Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases. The Journal of biological chemistry 94 11741929
2006 ADAM15 disintegrin is associated with aggressive prostate and breast cancer disease. Neoplasia (New York, N.Y.) 87 16756724
2008 ADAM15 supports prostate cancer metastasis by modulating tumor cell-endothelial cell interaction. Cancer research 74 18281484
2009 ADAM-9, ADAM-15, and ADAM-17 are upregulated in macrophages in advanced human atherosclerotic plaques in aorta and carotid and femoral arteries--Tampere vascular study. Annals of medicine 69 19253070
2010 ADAM15 regulates endothelial permeability and neutrophil migration via Src/ERK1/2 signalling. Cardiovascular research 65 20189953
2007 ADAM-15: a metalloprotease that mediates inflammation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 59 17905725
2003 Increased expression of disintegrin-metalloproteinases ADAM-15 and ADAM-9 following upregulation of integrins alpha5beta1 and alphavbeta3 in atherosclerosis. Journal of cellular biochemistry 56 12858346
2001 ADAM15 overexpression in NIH3T3 cells enhances cell-cell interactions. Experimental cell research 56 11697891
2005 Homeostatic effects of the metalloproteinase disintegrin ADAM15 in degenerative cartilage remodeling. Arthritis and rheumatism 54 15818704
2012 Exosome release of ADAM15 and the functional implications of human macrophage-derived ADAM15 exosomes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 53 22505472
2008 Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma. Molecular cancer research : MCR 51 18296648
2005 ADAM15 decreases integrin alphavbeta3/vitronectin-mediated ovarian cancer cell adhesion and motility in an RGD-dependent fashion. The international journal of biochemistry & cell biology 50 15618016
2002 ADAM15 is an adherens junction molecule whose surface expression can be driven by VE-cadherin. Experimental cell research 48 12243749
2009 Characterization of the catalytic activity of the membrane-anchored metalloproteinase ADAM15 in cell-based assays. The Biochemical journal 43 19207106
2004 ADAM-15 inhibits wound healing in human intestinal epithelial cell monolayers. American journal of physiology. Gastrointestinal and liver physiology 42 15358598
2005 Expression of ADAM15 in lung carcinomas. Virchows Archiv : an international journal of pathology 41 15756594
2014 MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression. PloS one 40 25333931
1999 Up-regulation of MDC15 (metargidin) messenger RNA in human osteoarthritic cartilage. Arthritis and rheumatism 39 10513811
2005 Expression of ADAM15 in rheumatoid synovium: up-regulation by vascular endothelial growth factor and possible implications for angiogenesis. Arthritis research & therapy 36 16277668
2001 Highly enhanced expression of the disintegrin metalloproteinase MDC15 (metargidin) in rheumatoid synovial tissue. Arthritis and rheumatism 34 11592366
2010 Activation of GRP78 on endothelial cell membranes by an ADAM15-derived peptide induces angiogenesis. Journal of vascular research 33 20145413
2013 TRIF-mediated TLR3 and TLR4 signaling is negatively regulated by ADAM15. Journal of immunology (Baltimore, Md. : 1950) 32 23365087
2006 ADAM15 upregulation and interaction with multiple binding partners in inflammatory bowel disease. Laboratory investigation; a journal of technical methods and pathology 30 16894352
2015 ADAM15 targets MMP9 activity to promote lung cancer cell invasion. Oncology reports 29 26323669
2012 ADAM15 deficiency attenuates pulmonary hyperpermeability and acute lung injury in lipopolysaccharide-treated mice. American journal of physiology. Lung cellular and molecular physiology 28 23161886
2009 The role of the disintegrin metalloproteinase ADAM15 in prostate cancer progression. Journal of cellular biochemistry 28 19229865
2008 ADAM15 suppresses cell motility by driving integrin alpha5beta1 cell surface expression via Erk inactivation. The international journal of biochemistry & cell biology 28 18387333
2016 ADAM15 Is Functionally Associated with the Metastatic Progression of Human Bladder Cancer. PloS one 27 26930657
2009 Src stimulates fibroblast growth factor receptor-2 shedding by an ADAM15 splice variant linked to breast cancer. Cancer research 27 19487280
2008 An Adam15 amplification loop promotes vascular endothelial growth factor-induced ocular neovascularization. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 18381816
2022 Integrin α3/α6 and αV are implicated in ADAM15-activated FAK and EGFR signalling pathway individually and promote non-small-cell lung cancer progression. Cell death & disease 26 35597804
2019 ADAM15 mediates upregulation of Claudin-1 expression in breast cancer cells. Scientific reports 26 31467400
2010 ADAM15 exerts an antiapoptotic effect on osteoarthritic chondrocytes via up-regulation of the X-linked inhibitor of apoptosis. Arthritis and rheumatism 26 20213810
2007 ADAM15 gene structure and differential alternative exon use in human tissues. BMC molecular biology 25 17937806
2004 Aberrant alternative exon use and increased copy number of human metalloprotease-disintegrin ADAM15 gene in breast cancer cells. Genes, chromosomes & cancer 25 15384173
2019 The metalloproteinase ADAM15 is upregulated by shear stress and promotes survival of endothelial cells. Journal of molecular and cellular cardiology 23 31271758
2008 Presence, processing, and localization of mouse ADAM15 during sperm maturation and the role of its disintegrin domain during sperm-egg binding. Reproduction (Cambridge, England) 22 18390692
2007 Inhibition of airway smooth muscle adhesion and migration by the disintegrin domain of ADAM-15. American journal of respiratory cell and molecular biology 22 17575078
2013 ADAM15 adds to apoptosis resistance of synovial fibroblasts by modulating focal adhesion kinase signaling. Arthritis and rheumatism 21 23918525
2009 Alternative splicing of ADAM15 regulates its interactions with cellular SH3 proteins. Journal of cellular biochemistry 18 19718658
2020 The microRNA miR-3174 Suppresses the Expression of ADAM15 and Inhibits the Proliferation of Patient-Derived Bladder Cancer Cells. OncoTargets and therapy 17 32547057
2017 Overexpression of the A Disintegrin and Metalloproteinase ADAM15 is linked to a Small but Highly Aggressive Subset of Prostate Cancers. Neoplasia (New York, N.Y.) 16 28282546
2013 Molecular implication of ADAM-15 and -17 in intrauterine adhesions. European journal of obstetrics, gynecology, and reproductive biology 16 23910172
2009 The therapeutic potential of ADAM15. Current pharmaceutical design 16 19601833
2005 ADAM9, ADAM10, and ADAM15 mRNA levels in the rat brain after kainic acid-induced status epilepticus. Brain research. Molecular brain research 16 15950787
2022 ADAM15 is required for optimal collagen cross-linking and scar formation following myocardial infarction. Matrix biology : journal of the International Society for Matrix Biology 15 34995785
2012 Differential expression of ADAM15 and ADAM17 metalloproteases in the rat brain after severe hypobaric hypoxia and hypoxic preconditioning. Neuroscience research 15 22230263
2012 ADAM15 protein amplifies focal adhesion kinase phosphorylation under genotoxic stress conditions. The Journal of biological chemistry 15 22544741
2010 ADAM-15 disintegrin-like domain structure and function. Toxins 15 22069559
2020 ADAM15 expression is increased in lung CD8+ T cells, macrophages, and bronchial epithelial cells in patients with COPD and is inversely related to airflow obstruction. Respiratory research 14 32677970
2013 Recombinant disintegrin domain of ADAM15 inhibits the proliferation and migration of Bel-7402 cells. Biochemical and biophysical research communications 14 23688428
2020 Interleukin 13 (IL-13)-regulated expression of the chondroprotective metalloproteinase ADAM15 is reduced in aging cartilage. Osteoarthritis and cartilage open 13 33381768
2018 ADAM15 in Apoptosis Resistance of Synovial Fibroblasts: Converting Fas/CD95 Death Signals Into the Activation of Prosurvival Pathways by Calmodulin Recruitment. Arthritis & rheumatology (Hoboken, N.J.) 13 30003689
2014 Characterization of oxygen-induced retinopathy in mice carrying an inactivating point mutation in the catalytic site of ADAM15. Investigative ophthalmology & visual science 13 25249606
2010 ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma. Biochemical and biophysical research communications 13 20851104
2006 Integrin binding characteristics of the disintegrin-like domain of ADAM-15. Thrombosis and haemostasis 13 17080222
2009 ADAM15 modulates outside-in signalling in chondrocyte-matrix interactions. Journal of cellular and molecular medicine 12 18774960
2021 ADAM15 Participates in Tick-Borne Encephalitis Virus Replication. Journal of virology 11 33208450
2013 ADAM15 is involved in MICB shedding and mediates the effects of gemcitabine on MICB shedding in PANC-1 pancreatic cancer cells. Molecular medicine reports 11 23314034
2021 NCK1-AS1 promotes the progression of melanoma by accelerating cell proliferation and migration via targeting miR-526b-5p/ADAM15 axis. Cancer cell international 10 34247598
2015 The ADAM15 ectodomain is shed from secretory exosomes. BMB reports 10 25208722
2004 Expression of splice variants of the human ADAM15 gene and strong interaction between the cytoplasmic domain of one variant and Src family proteins Lck and Hck. Pathobiology : journal of immunopathology, molecular and cellular biology 10 15263807
2011 Lack of ADAM15 in mice is associated with increased osteoblast function and bone mass. Biological chemistry 9 21801086
2006 Novel function of human ADAM15 disintegrin-like domain and its derivatives in platelet aggregation. Thrombosis research 9 16797059
2019 Endothelin 1, NF-κB, and ADAM-15 expression in diabetic foot wounds. Bratislavske lekarske listy 8 30685994
2012 Role of ADAM-15 in wound healing and melanoma development. Experimental dermatology 8 22621184
2022 Quantitative Proteomics Reveals That ADAM15 Can Have Proteolytic-Independent Functions in the Steady State. Membranes 7 35736286
2009 Expression of ADAM-15 in rat myocardial infarction. International journal of experimental pathology 7 19563617
2023 Loss of cancer cell-derived ADAM15 alters the tumor microenvironment in colorectal tumors. International journal of cancer 6 37602921
2022 Loss of ADAM15 Exacerbates Transition to Decompensated Myocardial Hypertrophy and Dilation Through Activation of the Calcineurin Pathway. Hypertension (Dallas, Tex. : 1979) 6 36330793
2013 Helping Eve overcome ADAM: G-quadruplexes in the ADAM-15 promoter as new molecular targets for breast cancer therapeutics. Molecules (Basel, Switzerland) 6 24317528
2023 Identification of membrane proteins regulated by ADAM15 by SUSPECS proteomics. Frontiers in molecular biosciences 5 37388246
2014 ADAM15 participates in fertilization through a physical interaction with acrogranin. Reproduction (Cambridge, England) 5 25392190
2025 Mechanical forces trigger invasive behavior in synovial fibroblasts through N-cadherin/ADAM15 -dependent modulation of LncRNA H19. Scientific reports 4 40118917
2021 A Novel Pro-Inflammatory Mechanosensing Pathway Orchestrated by the Disintegrin Metalloproteinase ADAM15 in Synovial Fibroblasts. Cells 4 34685689
2009 Identification of binding peptides of the ADAM15 disintegrin domain using phage display. Journal of biosciences 4 19550037
2008 Screening cellular proteins involved in the anti-proliferative effect of the ADAM15 disintegrin domain in murine melanoma cells. Oncology reports 4 18695922
2022 Detection of ADAM15 in urine from patients with bladder cancer. Analytical biochemistry 3 35810783
2010 Characterisation of the human ADAM15 promoter. Nephron. Experimental nephrology 3 21196774
2025 Loss of ADAM15 prevents necroptosis induction by partial RIPK1 degradation due to enhanced TNF-R1 surface expression and basal caspase-8 activation. Cell communication and signaling : CCS 2 41340056
2024 Digital spatial profiling of segmental outflow regions in trabecular meshwork reveals a role for ADAM15. PloS one 2 38394161
2018 Cell adhesion-induced transient interaction of ADAM15 with poly(A) binding protein at the cell membrane colocalizes with mRNA translation. PloS one 2 30265671
2008 [Improving production and bioactivity of recombinant human disintegrin domain of ADAM15 (rhADAM15) in Escherichia coli]. Wei sheng wu xue bao = Acta microbiologica Sinica 2 18956757
2025 A Disintegrin and Metalloprotease 15 (ADAM15) as a Potential Predictor of Distant Metastasis in Colorectal Cancer (CRC). Journal of clinical medicine 1 40725774
2024 ADAM15 in Fibroblasts: Improving the Matrix Remodeling by Blocking the Action of Transforming Growth Factor-β1. Annals of clinical and laboratory science 1 39048163
2026 ADAM15 promotes the progression and metastasis of hepatocellular carcinoma by activating the JNK/p38 pathway. Scientific reports 0 41986445
2025 TFDP1 overexpression promotes apoptosis of nucleus pulposus cells in intervertebral disc degeneration through regulating ADAM15/MMP9 axis. General physiology and biophysics 0 39815900
2024 Loss of ADAM15 in female mice does not worsen pressure overload cardiomyopathy, independent of ovarian hormones. American journal of physiology. Heart and circulatory physiology 0 38607341

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