Affinage

ADAM17

Disintegrin and metalloproteinase domain-containing protein 17 · UniProt P78536

Length
824 aa
Mass
93.0 kDa
Annotated
2026-06-09
100 papers in source corpus 42 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADAM17 (TACE) is a membrane-anchored, zinc-dependent metalloprotease that serves as a principal ectodomain sheddase, controlling inflammation, development, and tissue homeostasis by releasing the soluble forms of cell-surface proteins (PMID:9042103, PMID:11823465). It was originally defined as the TNF-α converting enzyme, cleaving the Ala76-Val77 bond of the 26 kDa pro-TNF-α precursor to liberate mature soluble TNF-α, with TACE-deficient mice releasing 80-90% less soluble TNF-α and showing markedly reduced serum TNF-α after LPS challenge (PMID:9042103, PMID:10415747). Beyond TNF-α, ADAM17 sheds a broad substrate repertoire including the EGFR-family ligands TGF-α, amphiregulin and HB-EGF (PMID:11823465), cytokine receptors (IL-6R, TNFR1, TNFR2) (PMID:27151651, PMID:34919140, PMID:28062509), adhesion and immune-receptor molecules (GPIbα/GPV, CXCR2, CD16, CD62L) (PMID:16179345, PMID:25412626, PMID:23487023, PMID:34367174), NRG1 type III (PMID:21666671), the KIT and p75NTR receptors (PMID:20501791, PMID:21411748), the insulin receptor (PMID:36018759), ACE2 (PMID:36313337), and PD-L1 (PMID:32363112). Through release of EGFR ligands, ADAM17 acts genetically upstream of EGFR signaling in mammary ductal development, cardiac development, and CNS/PNS myelination and remyelination, where conditional deletion impairs oligodendrocyte survival and myelination and is rescued by EGFR overexpression (PMID:18470483, PMID:12814936, PMID:14499647, PMID:25186737, PMID:26338334, PMID:21666671). Its catalytic activity is governed at multiple levels: regulated trafficking between cholesterol-rich lipid rafts and active non-raft membrane (PMID:17786981), constitutive clathrin-mediated internalization that limits surface enzyme (PMID:27731361), stimulus-induced intracellular threonine-735 phosphorylation via Trk/MEK and p38 MAPK pathways (PMID:21411748, PMID:31257400), allosteric control through non-active-site ectodomain epitopes and the transmembrane/juxtamembrane domains (PMID:21415364, PMID:32103528), negative regulation by the tetraspanin CD9 (PMID:21365281), and an obligate mutual-stabilization relationship with the rhomboid pseudoprotease iRhom2, which is required for substrate release and is itself destabilized in the absence of ADAM17 (PMID:32103528, PMID:32060096, PMID:34937930). Its transcription is directly activated by p53 and by HIF-1α, integrating ADAM17 into differentiation, tumor suppression, and inflammatory programs (PMID:22772468, PMID:31640947). Loss-of-function mutations in RHBDF2 (iRhom2) cause human immune dysregulation through defective ADAM17-dependent release of TNF and amphiregulin (PMID:34937930). Functionally, ADAM17-driven shedding shapes diverse pathologies, including atherosclerosis via TNFR2 (PMID:28062509), TNFR1/γ-secretase-dependent endothelial necroptosis and metastasis (PMID:34919140), kidney and cardiac fibrosis (PMID:27642633, PMID:36313337), IL-6 trans-signaling in lung cancer and pancreatitis (PMID:31257400, PMID:36215509), and tumor immune evasion through soluble PD-L1 (PMID:32363112).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1997 High

    Established the molecular identity of the protease that generates soluble TNF-α, answering which enzyme cleaves the membrane-anchored cytokine precursor.

    Evidence Protein purification, partial cloning, and in vitro cleavage assay defining the Ala76-Val77 cleavage site on pro-TNF-α

    PMID:9042103

    Open questions at the time
    • In vitro cleavage does not establish in vivo contribution
    • Other physiological substrates not yet defined
  2. 1999 High

    Demonstrated that TACE is the dominant TNF-α converting enzyme in living animals, not merely in vitro, validating it as the principal in vivo sheddase for this cytokine.

    Evidence TACE-deficient and bone-marrow-reconstituted mice with ELISA for soluble TNF-α after LPS challenge

    PMID:10415747

    Open questions at the time
    • Residual shedding implies additional proteases
    • Did not address non-TNF substrates
  3. 2002 High

    Expanded the substrate repertoire beyond TNF-α to EGFR-family ligands, reframing ADAM17 as a general sheddase coupling cell-surface ligand release to growth-factor signaling.

    Evidence Purified enzyme cleavage assays plus TACE-deficient keratinocyte rescue for TGF-α, amphiregulin, and HB-EGF

    PMID:11823465

    Open questions at the time
    • Relative physiological importance of each ligand not ranked
    • Tissue-specific substrate selection unresolved
  4. 2003 High

    Placed TACE genetically upstream of EGFR signaling in development, establishing the sheddase as a rate-limiting controller of EGFR ligand availability in vivo.

    Evidence Genetic epistasis in compound TACE-heterozygous × EGFR-hypomorphic mice and TACE-null heart phenotyping

    PMID:12814936 PMID:14499647

    Open questions at the time
    • Which specific ligand drives each developmental phenotype not fully dissected
    • Mechanism of activity regulation in vivo unknown
  5. 2006 Medium

    Clarified how the zymogen is held latent, showing the prodomain acts as a chaperone-like conformational restraint rather than via the canonical cysteine-switch.

    Evidence Site-directed mutagenesis of the prodomain with cell-based zymogen activity assays

    PMID:16679521

    Open questions at the time
    • Structural basis of conformational restraint not resolved
    • Single-study mechanistic model
  6. 2008 Medium

    Identified membrane microdomain partitioning as a control switch, showing cholesterol-dependent displacement from lipid rafts to non-raft regions activates shedding.

    Evidence Cell-based and cell-free membrane shedding assays with raft fractionation and ABCA1 knockdown

    PMID:17786981

    Open questions at the time
    • Molecular determinant of raft partitioning not identified
    • Single lab
  7. 2008 Medium

    Demonstrated that ADAM17-released amphiregulin acts as a paracrine signal across tissue compartments, establishing the directionality of the ADAM17→AREG→EGFR axis in mammary morphogenesis.

    Evidence Mammary tissue recombination/transplantation with soluble AREG rescue

    PMID:18470483

    Open questions at the time
    • Quantitative thresholds of paracrine signaling unknown
    • Single lab
  8. 2010 Medium

    Extended ADAM17 substrate biology to receptor-tyrosine-kinase shedding controlling cell fate, showing KIT ectodomain cleavage drives physiological germ cell apoptosis.

    Evidence Pharmacological gain/loss-of-function (ADAM17 vs ADAM10 selectivity) and PMA stimulation in rat testis culture

    PMID:20501791

    Open questions at the time
    • Relies on pharmacology rather than genetic ADAM17 loss
    • Single lab
  9. 2011 High

    Revealed phosphorylation-based activation and direct partner-mediated regulation, mapping Thr735 phosphorylation by Trk/MEK and identifying CD9 as a negative regulator binding ADAM17.

    Evidence Phosphosite mapping with MEK inhibitors and rescue (p75NTR); four orthogonal binding methods plus CD9 gain/loss-of-function shedding assays

    PMID:21365281 PMID:21411748

    Open questions at the time
    • Phosphatase counter-regulation not defined
    • How CD9 binding inhibits catalysis structurally unknown
  10. 2011 High

    Established a counterintuitive substrate that ADAM17 inactivates, showing NRG1 type III cleavage negatively regulates myelination, broadening sheddase outcomes beyond ligand activation.

    Evidence Conditional knockout and lentiviral knockdown in DRG/motor neurons with EM, electrophysiology, and PI3K assays

    PMID:21666671

    Open questions at the time
    • Whether NRG1 cleavage is regulated independently of EGFR-ligand shedding unclear
  11. 2012 High

    Identified transcriptional control by p53 and positioned ADAM17 within a tumor-suppressive NOTCH1 differentiation axis, linking sheddase abundance to cancer biology.

    Evidence Conditional KO mice, human SCC lines, ChIP and rescue experiments

    PMID:22772468

    Open questions at the time
    • Mechanism of TACE-NOTCH1 activation in this context not fully resolved
    • Generality across tumor types untested
  12. 2013 High

    Defined ADAM17's role in shaping immune effector function through receptor shedding and uncovered a non-canonical activation/secretion route in viral pathogenesis.

    Evidence Selective inhibitor with NK CD16/CD62L FACS and IFN-γ assays; HIV-Nef-driven paxillin/Pak phosphorylation, raft fractionation, and EV pro-TNF cleavage

    PMID:23317503 PMID:23487023

    Open questions at the time
    • NK functional readouts rely on pharmacology
    • Physiological relevance of EV-packaged ADAM17 beyond HIV unclear
  13. 2014 High

    Confirmed allosteric, non-active-site regulation and established ADAM17 as a genetic driver of EGFR-dependent oligodendrocyte survival and CNS myelination via rescue epistasis.

    Evidence Cross-domain inhibitory antibody with epitope mapping; conditional OP knockout with EGFR-overexpression rescue, EM, and behavior

    PMID:21415364 PMID:25186737

    Open questions at the time
    • Endogenous ligand for the allosteric site unknown
    • Which EGFR ligand is rate-limiting in OPs not fully isolated
  14. 2014 High

    Demonstrated stimulus-selective shedding of CXCR2 from neutrophils, distinguishing ADAM17-dependent receptor down-regulation from ligand-induced internalization and linking it to inflammatory recruitment.

    Evidence Selective inhibitor, blocking antibody, and gene-targeted mice with intravital microscopy

    PMID:25412626

    Open questions at the time
    • Signal coupling non-ligand stimuli to ADAM17 not defined
  15. 2016 High

    Resolved how subcellular trafficking and cleavage-site geometry govern activity and substrate selection, showing constitutive internalization limits surface enzyme and juxtamembrane spacing discriminates ADAM17 from ADAM10.

    Evidence Live-cell imaging, biotinylation, clathrin inhibitors; IL-6R stalk mutagenesis with chimeric spacing constructs

    PMID:27151651 PMID:27731361

    Open questions at the time
    • How GPCR stimulation activates surface enzyme without altering abundance unresolved
    • Generality of distance threshold across substrates untested
  16. 2016 High

    Established ADAM17 as a homeostatic brake on TNFR2 signaling and a driver of EGFR-dependent organ fibrosis, defining downstream pathway position by genetic rescue.

    Evidence Adam17 hypomorphic mice on Ldlr-/- with TNFR2 siRNA rescue; proximal-tubule conditional KO, hypomorphic, and inhibitor approaches with human biopsy correlation

    PMID:27642633 PMID:28062509

    Open questions at the time
    • Balance between protective and pathogenic shedding context-dependence not fully mapped
  17. 2018 Medium

    Connected nitric-oxide signaling to ADAM17 activation and iRhom2 upregulation driving NOTCH1 in cancer stem cells, integrating second-messenger pathways with sheddase output.

    Evidence sGC/cGMP/PKG pathway dissection with xenograft and patient HCC correlation

    PMID:30297396

    Open questions at the time
    • Direct molecular link from PKG to ADAM17 activation not shown
    • Single lab
  18. 2019 Medium

    Identified HIF-1α as a direct transcriptional activator of ADAM17 in macrophages, linking hypoxia/inflammatory signaling to sheddase-driven vascular pathology, and extended ADAM17 roles into neural blood-pressure control and viral entry.

    Evidence ChIP and macrophage HIF-1α inhibition in aortic dissection; neuron-specific knockdown with BP telemetry; ADAM17 inhibitor in HPV16 entry assays

    PMID:31107240 PMID:31564162 PMID:31640947

    Open questions at the time
    • Mechanistic link from neuronal ADAM17 to sympathetic outflow incomplete
    • Viral-entry role relies on pharmacology
  19. 2020 High

    Mechanistically dissected the iRhom2-ADAM17 partnership at the transmembrane/juxtamembrane interface and as an obligate mutual-stabilization pair, and broadened immune-evasion roles via PD-L1 shedding.

    Evidence TMD/JMD chimeric and patient-variant constructs in double-KO cells; endogenous iRhom2 stability assays in Adam17-/- cells; PD-L1 shedding and T-cell killing assays

    PMID:32060096 PMID:32103528 PMID:32363112

    Open questions at the time
    • Structural model of the ADAM17-iRhom2 interface not resolved
    • How interface controls substrate selectivity mechanistically unclear
  20. 2021 High

    Established ADAM17 as a sequential processing initiator in TNFR1-dependent endothelial necroptosis driving metastasis, and revealed a direct, catalysis-independent role as a viral entry receptor.

    Evidence Endothelial-specific conditional KO plus inhibition in necroptosis/metastasis; direct E2-binding pull-down, domain mapping, and cross-species cDNA rescue for CSFV; IL-15/CD62L NK feedback antibody study

    PMID:33684175 PMID:34367174 PMID:34919140

    Open questions at the time
    • How ADAM17 shedding and γ-secretase processing are coordinated unknown
    • Whether viral binding alters catalytic activity unaddressed
  21. 2021 High

    Connected the ADAM17 pathway to a human Mendelian immune disorder, showing RHBDF2/iRhom2 loss-of-function impairs ADAM17-dependent TNF and amphiregulin release.

    Evidence Human genetic disease study with functional cytokine-release validation and Rhbdf2-/- mouse infection models

    PMID:34937930

    Open questions at the time
    • Tissue-specific consequences of iRhom2 loss on ADAM17 substrate spectrum not fully mapped
  22. 2022 Medium

    Extended the substrate range to the insulin receptor and ACE2 and linked ADAM17 shedding to metabolic and cardiac-fibrotic disease via defined downstream pathways.

    Evidence Recombinant cleavage and inhibitor rescue for insulin receptor with human artery data; adenoviral knockdown/overexpression in diabetic hearts with TGF-β1/Smad3 readout; hypomorphic mice and prodomain inhibitor in pancreatitis with IL-6/STAT3 axis

    PMID:36018759 PMID:36215509 PMID:36313337

    Open questions at the time
    • In vivo contribution of ADAM17 to insulin-receptor shedding genetically untested
    • Mechanism activating ADAM17 in metabolic disease incompletely defined
  23. 2024 High

    Showed that ADAM17 sheddase activity, not abundance, is the regulated node, with IFN-I signaling suppressing ROS-dependent ADAM17 activity in Langerhans cells to drive photosensitivity in lupus.

    Evidence Multiple lupus mouse models, human LC validation, IFNAR blockade rescue, and LC-specific ADAM17 KO epistasis with ROS measurement

    PMID:38860651

    Open questions at the time
    • Molecular link from ROS to ADAM17 catalytic activation not defined
    • Relevant EGFR ligand in keratinocyte survival not isolated

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural and regulatory model explaining how trafficking, phosphorylation, iRhom interaction, redox state, and cleavage-site geometry are integrated to select among ADAM17's many substrates in a given cell remains unresolved.
  • No high-resolution structure of the active ADAM17-iRhom2 complex in the timeline
  • Mechanism converting diverse upstream stimuli into specific substrate selection unknown
  • Quantitative rules governing tissue-specific substrate preference undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016787 hydrolase activity 3 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-5357801 Programmed Cell Death 2
Partners
CD16CD9EGFRIL6RKITRHBDF2TNFR2

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 TACE/ADAM17 was purified and partially cloned as the metalloprotease responsible for cleaving the Ala76-Val77 bond of the 26 kDa pro-TNF-α precursor to generate the mature 17 kDa soluble TNF-α. Protein purification and partial cloning; in vitro cleavage assay Journal of neuroimmunology High 9042103
1999 TACE-deficient mice (lacking proteolytically active TACE) release 80-90% less soluble TNF-α than wild-type cells, and irradiated mice reconstituted with TACE-knockout hematopoietic stem cells have markedly reduced serum TNF-α after LPS challenge, establishing TACE as the major TNF-α converting enzyme in vivo. Genetic knockout mouse model; bone marrow reconstitution; ELISA for soluble TNF-α Annals of the New York Academy of Sciences High 10415747
2002 TACE/ADAM17 cleaves pro-TGF-α at both N- and C-terminal processing sites to release soluble TGF-α; TACE-deficient primary keratinocytes shed dramatically less TGF-α, and TACE re-expression rescued shedding. TACE also cleaves peptide substrates corresponding to processing sites of amphiregulin and HB-EGF and increases their shedding when transfected into TACE-deficient cells. In vitro cleavage assay with purified TACE; TACE-deficient cells + adenoviral TACE rescue; co-transfection; Western blot The Journal of biological chemistry High 11823465
2003 Genetic reduction of functional TACE dosage greatly exacerbates the open-eye defect of Egfr(wa-2/wa-2) newborns, placing TACE upstream of EGFR ligand availability in vivo during eye development. Epistasis in compound mutant mice (TACE heterozygous × EGFR hypomorphic wa-2 allele); phenotype scoring Annals of the New York Academy of Sciences High 12814936
2003 TACE/ADAM17 null mutant mice exhibit markedly enlarged fetal hearts with increased myocardial trabeculation, larger cardiomyocyte size, and increased proliferation. Molecular analysis showed reduced EGFR expression, attenuated ErbB4 cleavage, and altered MAPK activation in knockout hearts, indicating TACE-mediated ectodomain shedding is required for normal cardiac development. Genetic knockout mouse model (TACE ΔZn/ΔZn); histology; Western blot; immunostaining Developmental biology High 14499647
2005 Aspirin induces dose-dependent shedding of platelet surface GPIbα and GPV via ADAM17; shedding was completely blocked in mouse platelets expressing an inactive form of ADAM17 and by a broad-range metalloproteinase inhibitor, but occurred normally in COX-1-deficient platelets. FACS on whole blood; immunoprecipitation; Western blot; ADAM17-inactive knock-in mice; COX-1 knockout mice The Journal of biological chemistry High 16179345
2006 The TACE zymogen cysteine-switch motif in the prodomain is not required for maintaining the inactive precursor state or for secretion; the prodomain maintains latency and aids secretion by preventing the catalytic domain from adopting its native active conformation, resembling a molecular chaperone mechanism. Site-directed mutagenesis of prodomain; cell-based zymogen activity assays Cell biochemistry and biophysics Medium 16679521
2008 In Drosophila, TACE (dTACE) can activate Notch in a ligand-independent manner when overexpressed, whereas Kuzbanian (Kuz) requires Delta stimulation; TACE-dependent Notch cleavage in the developing nervous system can thus bypass ligand engagement. In vitro Drosophila cell model; overexpression and genetic manipulation; Notch reporter assays Cellular and molecular life sciences : CMLS Medium 18535782
2008 HDLs activate ADAM17-dependent shedding of TNFR1, TNFR2, and TNF by reducing cholesterol content of lipid rafts, displacing ADAM17 from rafts to non-raft membrane regions where it cleaves substrates; apoA1 mediates this through ABCA1-dependent cholesterol efflux. Cell-based shedding assays; lipid raft fractionation; cell-free isolated membrane assays; ADAM17 inhibitors; ABCA1 knockdown Journal of cellular physiology Medium 17786981
2008 ADAM17-mediated release of amphiregulin (AREG) from mammary ductal epithelial cells activates EGFR on stromal cells to drive ductal development; tissue recombination and transplantation showed that ADAM17 and AREG must be on epithelial cells and EGFR on stromal cells, and soluble AREG rescues ADAM17-deficient transplants. Mammary tissue recombination and transplantation; local AREG administration rescue experiment Journal of mammary gland biology and neoplasia Medium 18470483
2010 TACE/ADAM17 mediates physiological germ cell apoptosis during the first wave of spermatogenesis by cleaving the extracellular domain of the KIT receptor; pharmacological inhibition of TACE/ADAM17 (but not ADAM10) significantly prevented germ cell apoptosis, and PMA-induced TACE activation triggered KIT ectodomain cleavage and apoptosis in ex vivo testis culture. Pharmacological inhibition in vivo/ex vivo; PMA stimulation; immunostaining; Western blot; rat testis culture Reproduction (Cambridge, England) Medium 20501791
2011 TACE/ADAM17 cleaves neuregulin-1 (NRG1) type III in the EGF domain, inactivating it (assessed by loss of PI3K pathway activation), and thereby negatively regulates peripheral nervous system myelination. Lentiviral TACE knockdown in DRG neurons accelerates myelination onset and causes hypermyelination; motor neuron-specific TACE knockout mice are hypermyelinated and show aberrant myelination of small-caliber fibers. Lentiviral knockdown in DRG neuron co-cultures; conditional knockout mice (motor neuron-specific); electrophysiology; electron microscopy; PI3K pathway assays Nature neuroscience High 21666671
2011 The tetraspanin CD9 directly associates with ADAM17 on the cell surface (shown by co-immunoprecipitation, crosslinking, proximity ligation, and pull-down) and negatively regulates ADAM17 sheddase activity; CD9 antibody treatment or overexpression reduces TNF-α and ICAM-1 shedding, whereas CD9 silencing increases ADAM17 activity. Co-immunoprecipitation; crosslinking; proximity ligation assay; pull-down; CD9 siRNA knockdown; overexpression; shedding assays Cellular and molecular life sciences : CMLS High 21365281
2011 TrkA and TrkB receptor tyrosine kinases induce MEK-dependent phosphorylation of ADAM17 at intracellular threonine 735, activating ADAM17 to cleave p75NTR and produce its intracellular domain (p75NTR-ICD), which is required for neurotrophin-dependent Erk/Akt activation and neuronal survival. Phosphorylation site identification; MEK inhibitors; ADAM17 depletion; overexpression of p75NTR-ICD rescue; PC12 cell survival assays; primary cerebellar granule neurons FASEB journal High 21411748
2011 A selective cross-domain human antibody was developed that inhibits cell-surface TACE activity by targeting an epitope outside the metalloprotease active site, demonstrating that TACE ectodomain regions beyond the catalytic site can allosterically control activity. Two-step phage display antibody selection; cell-surface TACE activity assays; epitope mapping Proceedings of the National Academy of Sciences of the United States of America Medium 21415364
2012 p53 transcriptionally activates TACE/ADAM17 as a previously unidentified target gene; TACE then activates NOTCH1 signaling to induce epidermal differentiation and suppress squamous cell carcinoma. FOS negatively regulates this p53/TACE/NOTCH1 differentiation axis. Conditional knockout mice; pharmacological p53/AP-1 manipulation; human SCC cell lines; ChIP/transcriptional assays; rescue experiments The Journal of clinical investigation High 22772468
2013 ADAM17 is expressed by NK cells and its selective inhibition abrogates CD16 and CD62L shedding from activated NK cells; ADAM17 inhibition enhances interferon-γ production, particularly when NK cells are triggered through CD16. ADAM17-selective inhibitor; FACS for CD16/CD62L surface expression; NK cell stimulation assays; IFN-γ ELISA Blood Medium 23487023
2013 HIV Nef recruits paxillin and Eed to activate TACE/ADAM17 and ADAM10; Pak2 phosphorylates paxillin at Ser272/274 to promote TACE-paxillin association and shuttling into extracellular vesicles via lipid rafts, whereas Pak1 phosphorylates Ser258 to inhibit this association. Activated TACE in EVs cleaves proTNFα. Co-immunoprecipitation; phospho-specific mutagenesis; lipid raft fractionation; EV isolation; proTNFα cleavage assay; Pak1/2 kinase assays Molecular cell High 23317503
2013 ADAM17 inhibition or knockdown in diabetic mouse kidney cortex reduces Nox4 expression and NADPH oxidase activity, as well as type IV collagen and fibronectin accumulation, placing ADAM17 upstream of Nox4-mediated oxidative stress in diabetic nephropathy. ADAM17-selective inhibitor (TMI-005) in vivo; siRNA knockdown in cultured proximal tubular cells; Western blot; NADPH oxidase activity assay American journal of physiology. Renal physiology Medium 23678045
2014 TACE/ADAM17 genetic deletion in oligodendrocyte progenitor cells (OPs) impairs EGFR ligand (TGFα and HB-EGF) shedding, reduces EGFR signaling, causes premature cell cycle exit and reduced OL survival, and leads to deficits in CNS myelination and motor behavior. EGFR overexpression in TACE-deficient OPs rescues OL survival and myelination. Conditional knockout mice (NG2-Cre); EGFR overexpression rescue; immunohistochemistry; electron microscopy; behavioral tests; EGFR hypomorphic mouse epistasis The Journal of neuroscience High 25186737
2014 ADAM17 mediates CXCR2 shedding from neutrophil surfaces in response to non-ligand stimuli (but not chemokine ligand-induced internalization); ADAM17 inhibitor, blocking antibody, and ADAM17 gene-targeted mice all block CXCR2 down-regulation, and ADAM17 blockade enhances neutrophil recruitment during acute inflammation. ADAM17-selective inhibitor; function-blocking antibody; ADAM17 gene-targeted mice; FACS; intravital microscopy/acute inflammation model Journal of leukocyte biology High 25412626
2015 TACE/ADAM17 is required for oligodendrocyte regeneration and CNS remyelination following demyelination; TACE depletion in OPs abrogates EGFR activation in OL lineage cells and impairs cell expansion and survival. EGFR overexpression in TACE-deficient OPs restores OL regeneration and CNS remyelination. Conditional knockout mice; demyelination model; EGFR overexpression rescue; immunohistochemistry; electron microscopy The Journal of neuroscience High 26338334
2016 ADAM17 activity is controlled by subcellular localization: it is constitutively internalized via clathrin-coated pits, with only a small fraction at the cell surface. Physiological GPCR-ligand stimulation activates ADAM17 shedding without altering cell-surface abundance, whereas PMA/PKC activation causes rapid increase of mature ADAM17 at the cell surface followed by its internalization and degradation. Live-cell imaging; cell surface biotinylation; clathrin inhibitors; FACS; pulse-chase Scientific reports Medium 27731361
2016 In the IL-6 receptor (IL-6R), deletion of a triple serine motif (Ser-359 to Ser-361) adjacent to the cleavage site prevents ADAM17-mediated cleavage but not ADAM10-mediated cleavage, because it reduces the distance between the cleavage site and the plasma membrane below the threshold required for ADAM17. Site-directed mutagenesis of IL-6R stalk; cell-based shedding assays; chimeric receptor constructs with altered juxtamembrane spacing Scientific reports High 27151651
2016 Adam17 deficiency (hypomorphic mice) leads to increased membrane-resident TNFα and TNFR2 protein levels, constitutive TNFR2 signaling activation, and proatherosclerotic cellular functions (increased macrophage/VSMC proliferation, reduced apoptosis, increased adhesion); siRNA knockdown of TNFR2 rescues aberrant proliferation in Adam17-depleted cells, placing TNFR2 downstream of ADAM17 in this pathway. Adam17 hypomorphic mice crossed to Ldlr-/- background; siRNA TNFR2 rescue; cell proliferation/apoptosis assays; Western blot; atherosclerosis lesion analysis Arteriosclerosis, thrombosis, and vascular biology High 28062509
2016 ADAM17 substrate release in kidney proximal tubule (particularly pro-TNFα and amphiregulin) drives persistent EGFR activation leading to macrophage/neutrophil ingress and fibrosis; proximal tubule-specific inducible ADAM17 KO (Slc34a1-Cre), ADAM17 hypomorphic mice, and pharmacological ADAM17 inhibition all protect against kidney fibrosis. Conditional knockout mice; ADAM17 hypomorphic mice; ADAM17 inhibitor; EGFR phosphorylation assays; histology; urine AREG ELISA; human kidney biopsy analysis JCI insight High 27642633
2018 iNOS/NO activates TACE/ADAM17 through a soluble guanylyl cyclase/cGMP/PKG-dependent pathway and up-regulates iRhom2, leading to Notch1 cleavage and activation specifically in CD24+CD133+ liver cancer stem cells (LCSCs), promoting stemness and HCC aggressiveness. In vitro signaling pathway dissection (sGC/cGMP/PKG inhibitors); iRhom2 expression analysis; xenograft tumor model; patient HCC correlation Proceedings of the National Academy of Sciences of the United States of America Medium 30297396
2019 HIF-1α directly transcriptionally activates ADAM17 in macrophages (identified as a novel HIF-1α target gene by ChIP), and macrophage HIF-1α/ADAM17 signaling drives vascular inflammation and extracellular matrix degradation in aortic dissection. ChIP assay; ELISA; immunofluorescence; metabolomics; macrophage-specific HIF-1α inhibition (acriflavine); mouse aortic dissection models EBioMedicine Medium 31640947
2019 ADAM17 colocalizes with angiotensin-II type 1 receptors on Sim1 neurons in the hypothalamic paraventricular nucleus; selective neuronal ADAM17 knockdown reduces FosB expression, increases vagal tone, and prevents acute pressor response to centrally administered angiotensin-II, placing neuronal ADAM17 as a regulator of sympathetic outflow and blood pressure. Neuron-specific conditional knockdown mouse models; photoactivation; neuronal culture; angiotensin-II central injection; blood pressure telemetry Hypertension Medium 31564162
2019 ADAM17 is required for oncogenic HPV16 entry: ADAM17 proteinase activity sheds growth factors, activating ERK1/2 signaling that triggers formation of an endocytic entry platform consisting of enlarged CD151 domains containing EGFR. ADAM17 inhibitor; ERK1/2 pathway inhibitors; live-cell imaging; proximity assays for CD151/EGFR complex; virus infection assays eLife Medium 31107240
2020 ADAM10 and ADAM17 cleave PD-L1 from the surface of tumor cells and extracellular vesicles to produce a soluble active sPD-L1 fragment that induces CD8+ T cell apoptosis and impairs tumor cell killing by CD8+ T cells. ADAM10/17 inhibitor; cell-based shedding assay; CD8+ T cell apoptosis assay; tumor cell killing assay; correlation of PD-L1 protein-to-mRNA ratios with ADAM expression Oncoimmunology Medium 32363112
2020 The transmembrane domain (TMD) and extracellular juxtamembrane domain (JMD) of ADAM17 interact functionally with the TMD and JMD of iRhom2 to control ADAM17 stimulation and substrate selectivity. A point mutation in the ADAM17 JMD from a Tetralogy of Fallot patient specifically alters ADAM17 substrate selectivity toward HB-EGF. ADAM17 TMD chimeric/mutant constructs; Adam17-/- and iRhom1/2-/- cell rescue experiments; substrate-selective shedding assays; patient variant analysis FASEB journal High 32103528
2020 Endogenous iRhom2 protein stability requires the presence of ADAM17: iRhom2 is barely detectable in ADAM17-deficient mouse embryonic fibroblasts and macrophages, whereas iRhom1 levels are not reduced (slightly increased) without ADAM17, indicating iRhom2 and ADAM17 are obligate binding partners. Cell surface biotinylation; Western blot in Adam17-/- cells; LPS-stimulated bone marrow-derived macrophages The Journal of biological chemistry Medium 32060096
2020 NNK (tobacco carcinogen) upregulates p38 MAPK-dependent threonine phosphorylation of ADAM17, activating shedding of soluble IL-6 receptor (sIL-6R) which drives ERK MAPK trans-signaling; ADAM17 deficiency abrogates sIL-6R shedding and downstream ERK signaling in lung adenocarcinoma cells, and NNK-treated hypomorphic Adam17 mice show markedly reduced lung tumorigenesis. Adam17 hypomorphic mice in NNK carcinogenesis model; CRISPR KO and pharmacological inhibition in human lung cancer cells; p38 inhibitor; threonine phosphorylation assays; sIL-6R ELISA; ERK phosphorylation Western blot Carcinogenesis High 31257400
2021 ADAM17 on endothelial cells mediates TNFR1 ectodomain shedding, and subsequent processing of the remaining stub by γ-secretase is required for TNF-induced necroptosis; genetic ablation of ADAM17 in endothelial cells prevents tumor cell-induced endothelial necroptosis, extravasation, and lung metastasis. Endothelial-specific ADAM17 conditional KO mice; pharmacological ADAM17 inhibition; necroptosis assays; metastasis lung colonization model The Journal of experimental medicine High 34919140
2021 ADAM17 on classical swine fever virus (CSFV)-permissive cells directly binds the viral envelope protein E2 via its metalloproteinase domain in a zinc-dependent manner; ADAM17 loss eliminates E2 binding and viral entry, and re-expression of pig, human, or mouse ADAM17 rescues infection. Pull-down assay with soluble E2; ADAM17 KO cell line; ADAM17 cDNA rescue; domain mapping; CSFV infection assays PLoS pathogens High 33684175
2021 ADAM17 blockade with a monoclonal antibody markedly increases human NK cell proliferation driven by IL-15 both in vitro and in xenograft mice; this proliferative boost is dependent on CD62L, whose surface levels are increased by ADAM17 blockade, revealing a negative feedback loop in which IL-15-activated ADAM17 limits NK cell proliferation by shedding CD62L. ADAM17-blocking monoclonal antibody; in vitro proliferation assay; xenograft mouse model; CD62L blocking antibody epistasis Frontiers in immunology Medium 34367174
2021 Loss-of-function mutations in RHBDF2 (iRHOM2) cause defective ADAM17-dependent cleavage and release of TNF and amphiregulin in human patients, leading to immune dysregulation; Rhbdf2-/- mice show more severe pneumonia after P. aeruginosa challenge and worse colitis after Citrobacter infection than wild-type mice. Human genetic disease study with functional validation; Rhbdf2-/- mouse infection models; cytokine release assays Nature immunology High 34937930
2022 Active ADAM17 directly cleaves the insulin receptor (IR) beta subunit ectodomain from endothelial cells; ADAM17 overexpression or PMA-induced ADAM17 activation reduces IRα surface levels and impairs insulin signaling, which is rescued by ADAM17 inhibition (TAPI-0), and IR shedding is increased in arteries from T2D patients. In vitro cleavage assay with recombinant ADAM17 and IR; ADAM17 overexpression; TAPI-0 inhibitor rescue; cell surface biotinylation; human artery vasodilation assay American journal of physiology. Heart and circulatory physiology Medium 36018759
2022 ADAM17 knockdown reduces, while ADAM17 overexpression aggravates, cardiac fibrosis in diabetic mice by regulating ACE2 shedding and cardiac fibroblast-to-myofibroblast transformation through the TGF-β1/Smad3 signaling pathway. Adenovirus-mediated shRNA knockdown and ADAM17 overexpression in diabetic mouse hearts; echocardiography; histology; TGF-β1/Smad3 pathway Western blot; primary cardiofibroblasts Frontiers in pharmacology Medium 36313337
2022 ADAM17 mediates experimental pancreatitis by shedding TNFα and soluble IL-6R (sIL-6R), activating IL-6 trans-signaling/STAT3 axis; genetic (Adam17ex/ex hypomorphic mice) and pharmacological (ADAM17 prodomain inhibitor A17pro) ADAM17 targeting ameliorates acute and chronic pancreatitis. Adam17ex/ex hypomorphic mice; ADAM17 prodomain inhibitor; cerulein and NNK pancreatitis models; IL-6/STAT3 pathway assays; histology; human pancreatitis biopsy correlation Proceedings of the National Academy of Sciences of the United States of America High 36215509
2024 In lupus, IFN-I signaling inhibits Langerhans cell (LC) ADAM17 sheddase activity (without consistently reducing ADAM17 protein expression or LC numbers), leading to reduced EGFR ligand release and impaired keratinocyte survival after UV radiation; IFNAR blockade in lupus model mice restores LC ADAM17 sheddase activity via restoration of UVR-induced cytoplasmic reactive oxygen species, and this restoration reduces photosensitive responses in an LC ADAM17-dependent manner. Transcriptomic analysis; IFN-I treatment of murine and human LCs; IFNAR blocking antibody in three lupus mouse models; ROS measurement; ADAM17 sheddase activity assay; LC-specific ADAM17 genetic ablation epistasis eLife High 38860651

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17). Blood 452 23487023
2011 ADAM17: a molecular switch to control inflammation and tissue regeneration. Trends in immunology 434 21752713
2002 Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth factor receptor ligand availability. The Journal of biological chemistry 354 11823465
2010 ADAM-17: the enzyme that does it all. Critical reviews in biochemistry and molecular biology 338 20184396
2017 The shedding protease ADAM17: Physiology and pathophysiology. Biochimica et biophysica acta. Molecular cell research 276 28705384
2010 The "A Disintegrin And Metalloproteases" ADAM10 and ADAM17: novel drug targets with therapeutic potential? European journal of cell biology 256 21194787
2003 TACE/ADAM17 processing of EGFR ligands indicates a role as a physiological convertase. Annals of the New York Academy of Sciences 146 12814936
2009 ADAM17 as a therapeutic target in multiple diseases. Current pharmaceutical design 140 19601834
2018 iNOS promotes CD24+CD133+ liver cancer stem cell phenotype through a TACE/ADAM17-dependent Notch signaling pathway. Proceedings of the National Academy of Sciences of the United States of America 136 30297396
2019 Macrophage metabolic reprogramming aggravates aortic dissection through the HIF1α-ADAM17 pathway✰. EBioMedicine 122 31640947
2011 TACE (ADAM17) inhibits Schwann cell myelination. Nature neuroscience 120 21666671
2016 ADAM17 substrate release in proximal tubule drives kidney fibrosis. JCI insight 116 27642633
2020 ADAM10 and ADAM17 cleave PD-L1 to mediate PD-(L)1 inhibitor resistance. Oncoimmunology 105 32363112
2011 Cross-domain inhibition of TACE ectodomain. Proceedings of the National Academy of Sciences of the United States of America 104 21415364
2013 The role of ADAM17 in metabolic inflammation. Atherosclerosis 98 23384719
1999 Adamalysins. A family of metzincins including TNF-alpha converting enzyme (TACE). Annals of the New York Academy of Sciences 96 10415747
2016 Control of ADAM17 activity by regulation of its cellular localisation. Scientific reports 94 27731361
2013 ADAM17, shedding, TACE as therapeutic targets. Pharmacological research 90 23415892
2019 The metalloprotease ADAM17 in inflammation and cancer. Pathology, research and practice 89 30992230
1997 Structural features and biochemical properties of TNF-alpha converting enzyme (TACE). Journal of neuroimmunology 89 9042103
2003 TACE is required for fetal murine cardiac development and modeling. Developmental biology 87 14499647
2013 HIV Nef, paxillin, and Pak1/2 regulate activation and secretion of TACE/ADAM10 proteases. Molecular cell 86 23317503
2016 Cleavage Site Localization Differentially Controls Interleukin-6 Receptor Proteolysis by ADAM10 and ADAM17. Scientific reports 84 27151651
2011 The sheddase activity of ADAM17/TACE is regulated by the tetraspanin CD9. Cellular and molecular life sciences : CMLS 81 21365281
2007 Inhibition of ADAM17 reduces hypoxia-induced brain tumor cell invasiveness. Cancer science 81 17355261
2019 ACE2 and ADAM17 Interaction Regulates the Activity of Presympathetic Neurons. Hypertension (Dallas, Tex. : 1979) 76 31564162
2008 The ADAM17-amphiregulin-EGFR axis in mammary development and cancer. Journal of mammary gland biology and neoplasia 76 18470483
2014 ADAM17 at the interface between inflammation and autoimmunity. Immunology letters 70 25171914
2004 ADAM17 mRNA expression and pathological features of hepatocellular carcinoma. World journal of gastroenterology 66 15309730
2019 ADAM17: An Emerging Therapeutic Target for Lung Cancer. Cancers 62 31438559
2012 Differentiation-induced skin cancer suppression by FOS, p53, and TACE/ADAM17. The Journal of clinical investigation 59 22772468
2020 ADAM17-Mediated Shedding of Inflammatory Cytokines in Hypertension. Frontiers in pharmacology 58 32848763
2001 Astrocyte and endothelial cell expression of ADAM 17 (TACE) in adult human CNS. Glia 57 11360299
2016 Adam17 Deficiency Promotes Atherosclerosis by Enhanced TNFR2 Signaling in Mice. Arteriosclerosis, thrombosis, and vascular biology 56 28062509
2005 Aspirin induces platelet receptor shedding via ADAM17 (TACE). The Journal of biological chemistry 56 16179345
2021 Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis. The Journal of experimental medicine 52 34919140
2009 Differential expression and regulation of ADAM17 and TIMP3 in acute inflamed intestinal epithelia. American journal of physiology. Gastrointestinal and liver physiology 52 19299578
2019 Degradome of soluble ADAM10 and ADAM17 metalloproteases. Cellular and molecular life sciences : CMLS 51 31209506
2019 Role of ADAM17 in kidney disease. American journal of physiology. Renal physiology 46 31141400
2019 Status update on iRhom and ADAM17: It's still complicated. Biochimica et biophysica acta. Molecular cell research 46 31330158
2021 Contribution of ADAM17 and related ADAMs in cardiovascular diseases. Cellular and molecular life sciences : CMLS 45 33575814
2016 Targeting ADAM17 Sheddase Activity in Cancer. Current drug targets 45 27469341
2014 ADAM10 and ADAM17 have opposite roles during sprouting angiogenesis. Angiogenesis 45 25218057
2013 ADAM17 mediates Nox4 expression and NADPH oxidase activity in the kidney cortex of OVE26 mice. American journal of physiology. Renal physiology 45 23678045
2014 Deciphering the role of the ADAM17-dependent secretome in cell signaling. Journal of proteome research 41 24625128
2023 The protease ADAM17 at the crossroads of disease: revisiting its significance in inflammation, cancer, and beyond. The FEBS journal 39 37540030
2018 FoxM1 drives ADAM17/EGFR activation loop to promote mesenchymal transition in glioblastoma. Cell death & disease 39 29700308
2014 TACE/ADAM17 is essential for oligodendrocyte development and CNS myelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 39 25186737
2008 HDLs activate ADAM17-dependent shedding. Journal of cellular physiology 38 17786981
2017 Cezanne predicts progression and adjuvant TACE response in hepatocellular carcinoma. Cell death & disease 36 28880268
2022 Immunomodulatory role of metalloproteinase ADAM17 in tumor development. Frontiers in immunology 35 36466812
2014 MicroRNA-145 inhibits cell proliferation by directly targeting ADAM17 in hepatocellular carcinoma. Oncology reports 35 25174729
2013 ADAM17 promotes U87 glioblastoma stem cell migration and invasion. Brain research 35 23470260
2020 Blocking glycine receptors reduces neuroinflammation and restores neurotransmission in cerebellum through ADAM17-TNFR1-NF-κβ pathway. Journal of neuroinflammation 34 32917219
2011 Trk-dependent ADAM17 activation facilitates neurotrophin survival signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34 21411748
2014 Regulation of CXCR2 expression and function by a disintegrin and metalloprotease-17 (ADAM17). Journal of leukocyte biology 33 25412626
2016 The role of ADAM17 in tumorigenesis and progression of breast cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 32 27658778
2020 The ADAM17 protease promotes tobacco smoke carcinogen-induced lung tumorigenesis. Carcinogenesis 30 31257400
2016 Nox1 promotes colon cancer cell metastasis via activation of the ADAM17 pathway. European review for medical and pharmacological sciences 30 27874952
2008 Kuz and TACE can activate Notch independent of ligand. Cellular and molecular life sciences : CMLS 30 18535782
2019 ADAM17-dependent signaling is required for oncogenic human papillomavirus entry platform assembly. eLife 29 31107240
2016 Metalloproteinases ADAM10 and ADAM17 Mediate Migration and Differentiation in Glioblastoma Sphere-Forming Cells. Molecular neurobiology 29 27541285
2021 Abnormal ADAM17 expression causes airway fibrosis in chronic obstructive asthma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 34051616
2020 Substrate-selective protein ectodomain shedding by ADAM17 and iRhom2 depends on their juxtamembrane and transmembrane domains. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28 32103528
2017 Role of tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and associated proteins in coronary artery disease and cardiac events. Archives of cardiovascular diseases 28 29097110
2014 Dihydroartemisinin suppresses glioma proliferation and invasion via inhibition of the ADAM17 pathway. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 28 25301262
2022 Blockade of the protease ADAM17 ameliorates experimental pancreatitis. Proceedings of the National Academy of Sciences of the United States of America 27 36215509
2020 Shedding Light on COVID-19: ADAM17 the Missing Link? American journal of therapeutics 27 32769398
2020 Recent developments and strategies for the discovery of TACE inhibitors. Expert opinion on drug discovery 26 32281878
2013 ADAM17 regulates self-renewal and differentiation of U87 glioblastoma stem cells. Neuroscience letters 26 23356982
2021 Role of ADAM10 and ADAM17 in Regulating CD137 Function. International journal of molecular sciences 25 33800462
2007 Tackling EGFR signaling with TACE antagonists: a rational target for metalloprotease inhibitors in cancer. Expert opinion on therapeutic targets 25 17907959
2023 Transarterial chemoembolization (TACE) plus tyrosine kinase inhibitors versus TACE in patients with hepatocellular carcinoma: a systematic review and meta-analysis. World journal of surgical oncology 24 37004052
2006 The TACE zymogen: re-examining the role of the cysteine switch. Cell biochemistry and biophysics 24 16679521
2021 ADAM17 Deficiency Protects against Pulmonary Emphysema. American journal of respiratory cell and molecular biology 23 33181031
2022 Multi-targeting TACE/ADAM17 and gamma-secretase of notch signalling pathway in TNBC via drug repurposing approach using Lomitapide. Cellular signalling 22 36423860
2021 MiR-26a-5p alleviates cardiac hypertrophy and dysfunction via targeting ADAM17. Cell biology international 22 34370360
2020 ADAM17 stabilizes its interacting partner inactive Rhomboid 2 (iRhom2) but not inactive Rhomboid 1 (iRhom1). The Journal of biological chemistry 22 32060096
2015 Oligodendrocyte Regeneration and CNS Remyelination Require TACE/ADAM17. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 26338334
2014 Upregulation of APP, ADAM10 and ADAM17 in the denervated mouse dentate gyrus. PloS one 22 24404197
2010 TACE/ADAM17 is involved in germ cell apoptosis during rat spermatogenesis. Reproduction (Cambridge, England) 22 20501791
2009 TNF-alpha-converting enzyme (TACE/ADAM17)-dependent loss of CD30 induced by proteasome inhibition through reactive oxygen species. Leukemia 22 19890373
2021 Activation of ADAM17 by IL-15 Limits Human NK Cell Proliferation. Frontiers in immunology 21 34367174
2021 ADAM17 is an essential attachment factor for classical swine fever virus. PLoS pathogens 20 33684175
2012 Novel methods and strategies in the discovery of TACE inhibitors. Expert opinion on drug discovery 20 23231541
2024 Molecular mechanisms of TACE refractoriness: Directions for improvement of the TACE procedure. Life sciences 19 38428568
2023 Efficacy and safety analysis of TACE + Donafenib + Toripalimab versus TACE + Sorafenib in the treatment of unresectable hepatocellular carcinoma: a retrospective study. BMC cancer 18 37880661
2015 ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells. PloS one 18 26176220
2011 IL-1β and ADAM17 are central regulators of β-defensin expression in Candida esophagitis. American journal of physiology. Gastrointestinal and liver physiology 18 21233274
2010 Ectodomain shedding of Fcalpha receptor is mediated by ADAM10 and ADAM17. Immunology 18 20059578
2022 ADAM17 cleaves the insulin receptor ectodomain on endothelial cells and causes vascular insulin resistance. American journal of physiology. Heart and circulatory physiology 17 36018759
2020 Tetraspanin CD9 affects HPV16 infection by modulating ADAM17 activity and the ERK signalling pathway. Medical microbiology and immunology 17 32385608
2022 ADAM17 knockdown mitigates while ADAM17 overexpression aggravates cardiac fibrosis and dysfunction via regulating ACE2 shedding and myofibroblast transformation. Frontiers in pharmacology 16 36313337
2021 The -172 A-to-G variation in ADAM17 gene promoter region affects EGR1/ADAM17 pathway and confers susceptibility to septic mortality with sepsis-3.0 criteria. International immunopharmacology 16 34862128
2018 Impaired mechanical, heat, and cold nociception in a murine model of genetic TACE/ADAM17 knockdown. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 30586315
2014 ADAM17 mediates OSCC development in an orthotopic murine model. Molecular cancer 16 24495306
2024 The interferon-rich skin environment regulates Langerhans cell ADAM17 to promote photosensitivity in lupus. eLife 15 38860651
2021 Both Specific Endothelial and Proximal Tubular Adam17 Deletion Protect against Diabetic Nephropathy. International journal of molecular sciences 15 34073747
2021 Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease. Nature immunology 15 34937930
2012 Involvement of TACE/ADAM17 and ADAM10 in etoposide-induced apoptosis of germ cells in rat spermatogenesis. Journal of cellular physiology 15 21503882

Missed literature

Know a paper Affinage missed for ADAM17? Flag it for the maintainers and the community.

No submissions yet.