Affinage

ADAM12

Disintegrin and metalloproteinase domain-containing protein 12 · UniProt O43184

Length
909 aa
Mass
99.5 kDa
Annotated
2026-06-09
100 papers in source corpus 43 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADAM12 is a multidomain metalloprotease (transmembrane ADAM12-L and secreted ADAM12-S isoforms) that couples regulated ectodomain shedding to integrin- and adapter-mediated signaling to drive cell fusion, differentiation, adhesion remodeling, and tumor invasion (PMID:11786904, PMID:15574885, PMID:28468988). The enzyme is N-glycosylated in the ER and proteolytically matured in the trans-Golgi to an ~90 kDa form; its cytoplasmic domain governs ER exit and the prodomain α-helix is required for folding and processing, after which the cleaved prodomain remains non-covalently bound to mature enzyme in a compact clover-like four-domain structure (PMID:12000744, PMID:16455653). Mature ADAM12 sheds a broad substrate set — HB-EGF, E-cadherin, basigin, ephrin-A1, claudin-5, and endothelial junction/receptor molecules including VE-cadherin and Tie-2 — to transactivate EGFR and remodel cell–cell barriers (PMID:11786904, PMID:25909890, PMID:31013576, PMID:23686306, PMID:26242473, PMID:23458101). Catalytic activity is intrinsically inhibitable by N-TIMP-3 and TIMP-2 (but weakly by TIMP-1) and is allosterically gated by a heparan sulfate/prodomain cationic molecular switch that heparanase can relieve at the cell surface (PMID:18081311, PMID:18801731). Surface delivery of the active enzyme is controlled by PKCε acting through direct binding and the RACK1 scaffold, with PACSIN3 coupling the cytoplasmic tail to shedding (PMID:15364951, PMID:18621736, PMID:12952982). Beyond proteolysis, ADAM12 signals non-catalytically: it binds TβRII to promote Smad2 signaling and receptor endosomal trafficking (PMID:17620406), engages ILK through its cytoplasmic tail to activate PI3K/Akt survival signaling (PMID:22767580), associates with c-Src and αvβ3 integrin to assemble MMP-14-containing invadopodia and drive focal adhesion turnover (PMID:19769962, PMID:20951132, PMID:24006261, PMID:28468988), and uses its disintegrin/cysteine-rich domains to bind integrins α9β1 and α7β1 and syndecan-4, organizing actin, focal adhesions, and cell spreading (PMID:10944520, PMID:15242759, PMID:12509413). These activities underpin myoblast cell-cycle exit and fusion, chondrocyte proliferation during bone growth, trophoblast fusion, and Th1 T-cell costimulation, and they are amplified in cancer through hypoxia/HIF-, Notch-, Twist1-, and TGF-β/Smad-driven induction with post-transcriptional repression by miR-29 and miR-200 on the ADAM12-L 3'UTR (PMID:12972593, PMID:15574885, PMID:16869727, PMID:25909890, PMID:32572163, PMID:33952697, PMID:23589494, PMID:28468988, PMID:20457602, PMID:25886595).

Mechanistic history

Synthesis pass · year-by-year structured walk · 43 steps
  1. 2000 High

    Established that ADAM12's disintegrin domain mediates integrin-based cell-cell interaction, defining a non-proteolytic adhesive function distinct from canonical RGD-dependent binding.

    Evidence Recombinant disintegrin domain binding and cell adhesion assays with integrin α9β1

    PMID:10944520

    Open questions at the time
    • Did not map the binding interface residues
    • In vivo relevance of α9β1 engagement not addressed
  2. 2002 High

    Identified ADAM12 as a specific physiological HB-EGF sheddase driving EGFR transactivation, linking the protease to GPCR-evoked cardiac hypertrophy in vivo.

    Evidence Dominant-negative expression, direct inhibitor binding, mouse cardiac hypertrophy model

    PMID:11786904

    Open questions at the time
    • Substrate repertoire beyond HB-EGF not addressed
    • Did not resolve how shedding is spatially restricted
  3. 2002 High

    Defined the biosynthetic route of ADAM12, showing furin-type trans-Golgi maturation and that the cytoplasmic tail and prodomain α-helix control trafficking and folding.

    Evidence Prodomain/cytoplasmic mutagenesis, surface biotinylation, subcellular fractionation

    PMID:12000744

    Open questions at the time
    • Did not identify the maturation protease directly
    • Trafficking machinery for ER exit not defined
  4. 2002 High

    Connected ADAM12 to outside-in adhesion signaling by showing syndecan-4 acts as a receptor triggering β1-integrin-dependent spreading via PKCα/RhoA.

    Evidence Co-IP, PKC inhibitors, mutant syndecan-4, activated β1 integrin staining

    PMID:12509413

    Open questions at the time
    • Direct syndecan-4/ADAM12 binding stoichiometry not resolved
    • Link to proteolytic function unaddressed
  5. 2003 High

    Showed ADAM12 controls myoblast fate, with expression promoting cell-cycle arrest and quiescence markers via its disintegrin/cytoplasmic regions rather than its protease domain.

    Evidence siRNA, domain-deletion overexpression, cell cycle analysis in C2C12

    PMID:12972593

    Open questions at the time
    • Receptor mediating the non-proteolytic effect not defined here
    • Downstream effectors of p130/p27 induction unclear
  6. 2003 High

    Revealed that surface ADAM12 antagonizes β1 integrin function in preadipocytes, remodeling actin and promoting apoptosis rescuable by integrin activation.

    Evidence Co-IP, retroviral expression, adhesion assays, integrin-activating antibody rescue

    PMID:12915587

    Open questions at the time
    • Molecular basis of integrin impairment not resolved
    • Relationship to adipocyte differentiation in vivo untested
  7. 2003 High

    Identified PACSIN3 as a cytoplasmic-tail SH3 partner that couples ADAM12 to regulated proHB-EGF shedding.

    Evidence Yeast two-hybrid, GST pulldown, co-IP, siRNA, shedding assay

    PMID:12952982

    Open questions at the time
    • Mechanism by which PACSIN3 enhances shedding not defined
    • Endogenous physiological context limited
  8. 2003 Medium

    Placed ADAM12 transcription downstream of TGF-β via PI3K and MEK/ERK during hepatic stellate cell activation.

    Evidence Northern blot with PI3K and MEK inhibitors in HSC culture

    PMID:12717386

    Open questions at the time
    • Inhibitor-based pharmacology only, no genetic confirmation
    • Transcription factors not identified at this stage
  9. 2004 High

    Showed PKCε directly drives ADAM12 surface translocation, defining a kinase-dependent regulatory step controlling protease availability.

    Evidence Co-IP, PMA, myristoylated and kinase-dead PKCε mutants, surface immunostaining

    PMID:15364951

    Open questions at the time
    • Phosphorylation site mediating translocation not mapped
    • Did not yet implicate a scaffold
  10. 2004 Medium

    Demonstrated ADAM12 overexpression and HB-EGF shedding promote glioblastoma proliferation, extending the sheddase axis to tumor growth.

    Evidence qRT-PCR, in situ hybridization, ADAM inhibitor treatment of tumor tissue

    PMID:15509542

    Open questions at the time
    • Correlative tissue data with non-specific ADAM inhibitor
    • ADAM12-specific requirement not genetically isolated
  11. 2004 High

    Quantified ADAM12/α9β1 integrin interaction as a major driver of human myoblast fusion, particularly large myotube formation.

    Evidence Co-IP, antisense, anti-α9β1 blocking antibody, fusion quantification

    PMID:15574885

    Open questions at the time
    • The fusion machinery downstream of α9β1 engagement not defined
    • Residual fusion (~50%) involves unidentified factors
  12. 2004 Medium

    Expanded the integrin partner set by showing the disintegrin/cysteine-rich domains bind α7β1 with adhesion properties distinct from laminin.

    Evidence Affinity pulldown, adhesion assay, blocking antibody, FAK phospho-blot

    PMID:15242759

    Open questions at the time
    • Functional consequence of α7β1 binding in vivo unclear
    • Single-lab adhesion characterization
  13. 2005 High

    Defined cooperative interdomain function, showing the intact extracellular region supports myoblast adhesion and inhibits differentiation in a manner no single domain reproduces.

    Evidence Recombinant domains from S2 cells, adhesion/spreading assays, CD spectroscopy, differentiation markers

    PMID:15849365

    Open questions at the time
    • The myoblast receptor for intact ectodomain not identified
    • Structural basis of cooperativity not resolved
  14. 2005 Medium

    Refined the integrin receptor hierarchy, establishing α9β1 as primary with alternate β1 integrins as backups and PI3K dependence for spreading.

    Evidence Adhesion assays with ADAM12 fragments/mutants, blocking antibodies, PI3K inhibitor

    PMID:16061220

    Open questions at the time
    • Single-lab in vitro adhesion model
    • Selectivity rules among β1 integrins not fully defined
  15. 2005 Medium

    Linked ADAM12 protease activity to Aβ-induced neuronal death through the FISH adapter, implicating sheddase activation in neurotoxicity.

    Evidence Protease-dead mutant, FISH truncation, cleavage-product detection, neuronal death assay

    PMID:15710903

    Open questions at the time
    • Relevant shed substrate driving death not identified
    • Single-lab functional model
  16. 2005 Medium

    Dissected the TGF-β-driven induction cascade, showing both PI3K/mTOR/p70S6K and MEK/ERK branches are required for ADAM12 expression.

    Evidence Rapamycin, LY294002, UO126, phospho-p70S6K blots in HSCs

    PMID:16139919

    Open questions at the time
    • Pharmacology-only with no genetic confirmation
    • Transcription factor endpoints not identified here
  17. 2005 Low

    Identified FLRG as a cysteine-rich-domain partner linked to osteoclast differentiation, though the assay primarily tested FLRG rather than ADAM12.

    Evidence Yeast two-hybrid, osteoclast differentiation assay with recombinant FLRG

    PMID:15574124

    Open questions at the time
    • Awaits biochemical co-IP validation of the interaction
    • ADAM12's direct role in osteoclastogenesis not tested
  18. 2006 High

    Demonstrated in vivo that ADAM12-S protease activity promotes longitudinal bone growth by modulating chondrocyte proliferation and adhesion.

    Evidence Transgenic mice, BrdU, catalytically dead truncation, chondrocyte adhesion assays

    PMID:16869727

    Open questions at the time
    • The chondrocyte substrate cleaved was not identified
    • Mechanism of adhesion inhibition unresolved
  19. 2006 High

    Established the architecture of the mature/prodomain complex, showing retained non-covalent prodomain association and a compact clover-like structure.

    Evidence Domain-specific antisera, immunoprecipitation, negative-stain EM

    PMID:16455653

    Open questions at the time
    • High-resolution structure not obtained
    • Functional role of retained prodomain in activity not defined here
  20. 2007 High

    Revealed a protease-independent signaling role: ADAM12 binds TβRII to enhance Smad2 signaling and stabilize the receptor in endosomes by blocking Smad7.

    Evidence Co-IP, catalytically dead mutants, endosomal fractionation, Smad reporter

    PMID:17620406

    Open questions at the time
    • Direct binding interface on TβRII not mapped
    • Generality across TGF-β-responsive cell types untested
  21. 2007 High

    Characterized ADAM12-S catalytic mechanism, defined noncatalytic C-terminal regulation, and established the TIMP inhibition profile (N-TIMP-3 > TIMP-2 >> TIMP-1).

    Evidence In vitro kinetics with recombinant protein and domain mutants, N-terminal sequencing

    PMID:18081311

    Open questions at the time
    • Physiological substrate specificity not addressed
    • Structural basis of TIMP selectivity unresolved
  22. 2008 High

    Uncovered an allosteric heparan sulfate/prodomain cationic switch regulating sheddase activity, relieved by heparanase at the cell surface.

    Evidence In vitro sheddase assays, heparanase and polyanion treatment, cell-based shedding

    PMID:18801731

    Open questions at the time
    • Switch residues not fully mapped
    • In vivo contribution of proteoglycan regulation untested
  23. 2008 High

    Identified RACK1 as the scaffold assembling a RACK1/ADAM12/PKC ternary complex required for PKC-dependent membrane translocation.

    Evidence Yeast two-hybrid, co-IP of ternary complex, siRNA, fractionation

    PMID:18621736

    Open questions at the time
    • RACK1 binding site on ADAM12 not mapped
    • Quantitative contribution to surface pool not defined
  24. 2009 High

    Defined a reciprocal ADAM12-L/c-Src relationship in which two cytoplasmic SH3-binding sites recruit Src and ADAM12 enhances Src activity upon integrin engagement.

    Evidence Co-IP, colocalization, SH3 binding, kinase-dead Src, tyrosine phospho-blot

    PMID:19769962

    Open questions at the time
    • Functional consequence of ADAM12 tyrosine phosphorylation unclear
    • Downstream Src targets not defined here
  25. 2009 Medium

    Identified an MMP-7/ADAM12 transcriptional axis in agonist-induced hypertension and cardiac hypertrophy in vivo.

    Evidence RNAi, antisense, MMP-7 knockout, qRT-PCR, rodent hypertension models

    PMID:19398663

    Open questions at the time
    • Mechanism by which MMP-7 controls ADAM12 transcription unresolved
    • Single-lab in vivo correlation
  26. 2010 High

    Mapped a non-catalytic invadopodia function requiring the c-Src interaction site, αvβ3 integrin, and recruitment of caveolin-1 and MT1-MMP.

    Evidence Antibody ligation, domain mutants, cholesterol depletion, shedding assay

    PMID:20951132

    Open questions at the time
    • Physiological ligand triggering invadopodia not identified
    • Order of assembly of the cluster unresolved
  27. 2010 Medium

    Placed SnoN as a Smad-dependent repressor whose derepression mediates TGF-β1 induction of ADAM12, refining the transcriptional logic.

    Evidence Smad2/3 reporter, SnoN shRNA and overexpression, qRT-PCR, Western blot

    PMID:20457602

    Open questions at the time
    • Direct promoter occupancy not shown
    • Single-lab cell context
  28. 2010 High

    Engineered N-TIMP-2 variants showing ADAM12 has distinctive structural inhibition requirements, providing selective inhibitor leads.

    Evidence Kinetics with fluorescent peptide, N-TIMP-2 mutagenesis, cell-based shedding

    PMID:20533908

    Open questions at the time
    • Co-crystal structure of inhibitor complex not obtained
    • In vivo efficacy untested
  29. 2011 High

    Defined a Notch→miR-29 circuit that isoform-selectively up-regulates ADAM12-L through CSL/IKK signaling and relief of 3'UTR repression.

    Evidence Active Notch1, CSL reporter, IKK inhibitor, miR-29 target validation, qRT-PCR

    PMID:21518768

    Open questions at the time
    • Direct Notch target gene driving miR-29 suppression unclear
    • Physiological setting limited
  30. 2011 High

    Showed cancer-associated D301H/G479E mutations cause ER retention, block surface trafficking and Delta-like 1 shedding, and act dominant-negatively.

    Evidence Mutagenesis, surface biotinylation, immunofluorescence, shedding and dominant-negative assays

    PMID:18241035

    Open questions at the time
    • Functional consequence of loss-of-trafficking in tumors untested
    • Whether mutations are drivers unresolved
  31. 2012 High

    Identified ILK as a cytoplasmic-tail partner mediating protease-independent PI3K/ILK/Akt survival signaling and focal adhesion redistribution.

    Evidence Co-IP, siRNA, tail-deletion mutant, Akt phospho-blot, ILK kinase assay

    PMID:22767580

    Open questions at the time
    • ILK binding motif on ADAM12 tail not mapped
    • Survival phenotype in vivo untested
  32. 2013 High

    Demonstrated ADAM12 redistributes and activates MMP-14 within an αvβ3-dependent complex to degrade ECM and reduce apoptosis, independent of its own catalysis.

    Evidence Colocalization, MMP-14 activity assays, antibodies, domain mutants, orthotopic implantation

    PMID:24006261

    Open questions at the time
    • Direct ternary complex not biochemically isolated
    • Mechanism of MMP-14 activation unresolved
  33. 2013 Medium

    Connected ADAM12 to metastatic niche permeability via TGF-β1-stimulated ephrin-A1 shedding that disrupts EphA1/ephrin-A1 adhesion in lung.

    Evidence Yeast two-hybrid, cleavage assay, neutralizing antibody, lung metastasis model

    PMID:23686306

    Open questions at the time
    • Direct ADAM12 cleavage of ephrin-A1 vs indirect not fully resolved
    • Single-lab in vivo model
  34. 2013 Medium

    Expanded the substrate repertoire to endothelial junction and receptor proteins (VE-cadherin, Tie-2, Flk-1, VCAM-1, Kitl1) in cytokine-driven shedding.

    Evidence Shedding screen, siRNA, Western blot of shed forms

    PMID:23458101

    Open questions at the time
    • Direct vs indirect cleavage not distinguished for all hits
    • Physiological context limited to endothelial cells
  35. 2013 High

    Established a hypoxia-driven Notch-ADAM12-HB-EGF-EGFR invasion axis controlling invadopodia formation.

    Evidence Notch inhibition, ADAM12 KD/OE, shedding and invadopodia assays

    PMID:23589494

    Open questions at the time
    • How hypoxia couples to Notch in this axis not fully resolved
    • In vivo metastasis not tested in this study
  36. 2015 High

    Identified E-cadherin as a substrate whose shedding by ADAM12 promotes trophoblast fusion under PKA transcriptional control.

    Evidence siRNA, ADAM12S overexpression, E-cadherin shedding, PKA inhibitor, two fusion models

    PMID:25909890

    Open questions at the time
    • Whether E-cadherin shedding alone is sufficient for fusion unclear
    • PKA-responsive promoter elements not mapped
  37. 2015 High

    Showed ADAM12-L induces EMT via the cytoplasmic tail and Smad3/Akt/ERK signaling independent of protease activity, distinguishing isoform functions.

    Evidence Domain mutant overexpression, EMT/phospho-signaling blots, TβR and ERK inhibitors

    PMID:26407179

    Open questions at the time
    • Direct tail effector linking to Smad3 unidentified
    • Single cell-line model
  38. 2015 High

    Defined isoform-selective post-transcriptional control, with miR-29b/c and miR-200b/c directly repressing the ADAM12-L 3'UTR.

    Evidence miRNA mimics, 3'UTR luciferase with mutated sites, metabolic labeling, miRNA inhibitors

    PMID:25886595

    Open questions at the time
    • Relative dominance of each miRNA in vivo unclear
    • Upstream control of these miRNAs in tumors not addressed here
  39. 2015 Medium

    Linked ADAM12 to neural vascular barrier regulation via claudin-5 shedding under hypoxia.

    Evidence Metalloprotease inhibition, ADAM12/ADAM17 knockdown, TEER, in vivo barrier assay

    PMID:26242473

    Open questions at the time
    • Overlapping ADAM17 contribution not fully separated
    • Direct claudin-5 cleavage not biochemically proven
  40. 2017 High

    Placed ADAM12 downstream of Twist1 as a required effector of invasion/metastasis, with distinct domain requirements for invadopodia versus focal adhesion turnover.

    Evidence Knockdown, 3D organoid invasion, xenograft metastasis, live-imaging, domain mutants

    PMID:28468988

    Open questions at the time
    • Twist1 direct binding to ADAM12 promoter not shown
    • Mechanism coupling domains to adhesion turnover unresolved
  41. 2019 High

    Validated basigin as a direct ADAM12 substrate using CRISPR knockout and rescue, with detectable endogenous shed fragments.

    Evidence Co-IP, AP shedding reporter, CRISPR KO and re-expression, endogenous fragment detection

    PMID:31013576

    Open questions at the time
    • Functional consequence of basigin shedding not addressed
    • Physiological trigger of cleavage unclear
  42. 2020 High

    Revealed a non-classical immune role: ADAM12 is a T-cell costimulatory molecule selectively driving T-bet/IFNγ Th1 differentiation and Th1-mediated neuroinflammation.

    Evidence Fab antibody stimulation, knockout mice, shRNA, EAE model, transcriptomics

    PMID:32572163

    Open questions at the time
    • Receptor/ligand mediating costimulation not identified
    • Whether protease activity is involved unclear
  43. 2021 High

    Established a HIF→ADAM12→HB-EGF→EGFR→FAK hypoxia axis driving breast cancer migration and lung metastasis in vivo.

    Evidence HIF KD/OE, ADAM12 siRNA, shedding and phospho-EGFR/FAK blots, orthotopic metastasis model

    PMID:33952697

    Open questions at the time
    • Direct HIF binding to ADAM12 promoter not shown here
    • Contribution of other shed substrates to metastasis unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse non-catalytic scaffolding functions (TβRII, ILK, c-Src, integrins) are integrated with regulated proteolysis to produce context-specific outputs, and the receptors mediating ADAM12's adhesive and immune-costimulatory roles, remain unresolved.
  • No high-resolution structure of the active enzyme-prodomain complex with bound substrate
  • Receptor mediating T-cell costimulation unidentified
  • Coordination between shedding and adapter signaling in a single cell context not reconstituted

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0098631 cell adhesion mediator activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0016787 hydrolase activity 3 GO:0060090 molecular adaptor activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 4 GO:0005576 extracellular region 3 GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 2 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-1266738 Developmental Biology 4 R-HSA-1474244 Extracellular matrix organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 1
Partners
ILKITGA9PACSIN3PKCΕRACK1SDC4SRCTGFBR2
Complex memberships
ADAM12/αvβ3/MMP-14 invadopodial complexRACK1/ADAM12/PKCε ternary complex

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 ADAM12 functions as the specific sheddase for HB-EGF in cardiomyocytes; dominant-negative ADAM12 expression abrogated GPCR-agonist-induced HB-EGF shedding and subsequent EGFR transactivation leading to cardiac hypertrophy. The inhibitor KB-R7785 was shown to bind directly to ADAM12. Dominant-negative expression, direct binding assay, in vivo mouse model of cardiac hypertrophy Nature medicine High 11786904
2000 The disintegrin domains of ADAM12 (and ADAM15) interact specifically with integrin α9β1 in an RGD-independent manner, supporting cell-cell interaction. Recombinant domain binding assay, cell adhesion and cell-cell interaction assays The Journal of biological chemistry High 10944520
2003 TGF-β induces ADAM12 expression in activated hepatic stellate cells via PI3K and MEK/ERK pathways; ADAM12 expression is up-regulated during the quiescent-to-activated transition of hepatic stellate cells. Northern blot, PI3K inhibitor (LY294002) and MEK inhibitor (UO126) treatment, rat/human HSC culture Hepatology Medium 12717386
2002 ADAM12 is N-glycosylated in the ER and proteolytically processed in the trans-Golgi network to an ~90 kDa mature form lacking the prodomain; the cytoplasmic domain regulates ER exit, and the prodomain α-helical region is required for proper folding and processing. Mutagenesis (L73P prodomain mutation), cell surface biotinylation, subcellular fractionation, Western blot The Journal of biological chemistry High 12000744
2002 ADAM12 cysteine-rich domain engages syndecan-4 as a primary receptor, triggering β1 integrin-dependent cell spreading, stress fiber assembly, and focal adhesion formation through a PKCα/RhoA signaling axis. Co-immunoprecipitation, PKC inhibitors, mutant syndecan-4 transfection, activated β1 integrin staining (12G10) The Journal of biological chemistry High 12509413
2003 ADAM12 surface expression in preadipocytes forms complexes with β1 integrin (co-immunoprecipitation), impairs β1 integrin function, reorganizes actin stress fibers into a cortical network, reduces focal adhesions and fibronectin adhesion, and promotes apoptosis that can be rescued by β1-activating antibodies. Co-immunoprecipitation, retroviral transduction, immunostaining, Triton X-100 extraction, cell adhesion assays Journal of cell science High 12915587
2003 PACSIN3, identified via yeast two-hybrid screening, binds the proline-rich region (aa 829–840) of ADAM12's cytoplasmic domain via its SH3 domain, and co-localizes with ADAM12; PACSIN3 overexpression enhances TPA-induced proHB-EGF shedding, while PACSIN3 siRNA knockdown attenuates it. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, co-localization, siRNA knockdown, ectodomain shedding assay The Journal of biological chemistry High 12952982
2004 ADAM12 was found to be selectively overexpressed in glioblastomas and promotes cell proliferation through shedding of HB-EGF; ADAM inhibitor treatment reduced soluble HB-EGF in glioblastoma samples. Quantitative RT-PCR, in situ hybridization, immunoblotting, ADAM inhibitor treatment The American journal of pathology Medium 15509542
2004 PKCε induces ADAM12 translocation to the cell surface, requiring catalytic activity of PKCε; both C1 and C2 domains of PKCε contain binding sites for ADAM12, and co-immunoprecipitation from membrane fractions confirmed the interaction. Co-immunoprecipitation, PMA treatment, myristoylated PKCε transfection, kinase-inactive mutant, cell surface immunostaining The Journal of biological chemistry High 15364951
2003 ADAM12 expression level is higher in proliferating C2C12 myoblasts and reserve cells than in myotubes; siRNA knockdown of ADAM12 reduces expression of quiescence markers (p130, p27) and differentiation markers; overexpression of ADAM12 induces cell cycle arrest via upregulation of p130/p27 and downregulation of MyoD. The disintegrin-to-transmembrane region and cytoplasmic domain (but not metalloprotease domain) are required for ADAM12-mediated cell cycle arrest. siRNA knockdown, overexpression, domain deletion mutants, cell cycle analysis, Western blot Molecular and cellular biology High 12972593
2004 ADAM12 and α9β1 integrin are co-expressed during human myogenic precursor cell (mpc) differentiation, co-immunoprecipitate, and their interaction (inhibited by ADAM12 antisense or anti-α9β1 antibody) accounts for ~47–48% of myotube fusion, particularly affecting formation of large myotubes. Co-immunoprecipitation, antisense oligonucleotides, blocking antibody, fusion quantification assay Molecular biology of the cell High 15574885
2006 After furin cleavage of the ADAM12-S prodomain in the trans-Golgi, the ~25 kDa prodomain remains non-covalently associated with the ~68 kDa mature ADAM12-S. Electron microscopy revealed a compact clover-like four-domain structure for the full-length ADAM12-S molecule. Domain-specific antisera, immunoprecipitation, Western blot of serum and recombinant ADAM12, negative-stain electron microscopy The Journal of biological chemistry High 16455653
2007 ADAM12 interacts with TGF-β type II receptor (TβRII) and facilitates TGF-β signaling (Smad2 phosphorylation, Smad2/Smad4 association, transcriptional activation) independently of its protease activity; ADAM12 promotes accumulation of TβRII in early endosomes and stabilizes TβRII by suppressing its association with Smad7. Co-immunoprecipitation, dominant-negative and catalytically inactive ADAM12 mutants, endosomal fractionation, Smad reporter assay The Journal of cell biology High 17620406
2007 Human ADAM12-S catalytic properties: cleavage of S-carboxymethylated transferrin at multiple sites; noncatalytic C-terminal domains regulate activity; N-TIMP-3 inhibits ADAM12-S with low nanomolar Ki; TIMP-2 inhibits with slightly lower affinity; TIMP-1 is a much weaker inhibitor; NaCl inhibits ADAM12. In vitro enzymatic assay with recombinant ADAM12-S and domain deletion mutants, kinetic analysis, N-terminal sequencing Biochemistry High 18081311
2008 Heparan sulfate and heparin regulate ADAM12 activity through a prodomain/catalytic domain cationic molecular switch; endogenous cell surface proteoglycans also regulate this switch; human heparanase can promote ADAM12 sheddase activity at the cell surface by cleaving inhibitory heparan sulfate. In vitro sheddase assays, heparanase treatment, cell-based shedding assay, polyanion treatment The Journal of biological chemistry High 18801731
2008 RACK1 (receptor for activated PKC) was identified as an ADAM12 interacting protein by yeast two-hybrid; PKC-dependent phorbol ester treatment enhances co-immunoprecipitation of a ternary RACK1/ADAM12/PKC complex and ADAM12 membrane translocation; siRNA knockdown of RACK1 diminishes PMA-dependent ADAM12 membrane translocation in hepatic stellate cells. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, subcellular fractionation, phorbol ester stimulation The Journal of biological chemistry High 18621736
2004 The disintegrin and cysteine-rich (DC) domains of ADAM12 bind integrin α7β1; α7X1 and α7X2 splice variants support equal adhesion to DC domain; adhesion to DC differs from laminin in Mn2+ requirements and does not trigger FAK Tyr397 phosphorylation or efficient spreading. Affinity column pulldown, cell adhesion assay, blocking antibody, FAK phosphorylation Western blot Experimental cell research Medium 15242759
2005 The intact extracellular domain of ADAM12 (metalloprotease + disintegrin/cysteine-rich domains together) supports myoblast-specific adhesion and spreading not mediated by β1 integrins or proteoglycans, and inhibits differentiation (reduces p21 and myogenin); neither the metalloprotease domain nor the disintegrin/cysteine-rich fragment alone recapitulates this activity, indicating cooperative interdomain interaction. Recombinant domain production in Drosophila S2 cells, cell adhesion/spreading assays, far-UV circular dichroism, Western blot for differentiation markers The Journal of biological chemistry High 15849365
2005 In cell adhesion assays, α9β1 integrin is the primary receptor for ADAM12; when α9β1 is absent, other β1 family integrins can serve as alternate receptors; the disintegrin domain alone supports only α9 integrin-dependent attachment, while full-length ADAM12 supports additional integrin-mediated attachment; cell spreading requires PI3K activity. Cell adhesion assays with recombinant ADAM12 fragments and mutants, blocking antibodies, PI3K inhibitor Experimental cell research Medium 16061220
2005 TGF-β1-induced ADAM12 expression in hepatic stellate cells requires both the PI3K/Frap-mTOR/p70S6K and MEK/ERK pathways; rapamycin (mTOR inhibitor) blocks p70S6K phosphorylation and ADAM12 induction, while basal ADAM12 expression depends on PI3K/Akt/GSK-3 signaling. PI3K inhibitor (LY294002), MEK inhibitor (UO126), rapamycin treatment, Western blot for phospho-p70S6K Journal of hepatology Medium 16139919
2006 ADAM12-S transgenic mice exhibit increased longitudinal bone growth through modulation of chondrocyte proliferation and maturation; mice expressing a truncated metalloprotease-deficient ADAM12-S showed no bone length alterations, indicating protease activity is required. ADAM12-S inhibits chondrocyte adhesion to fibronectin and collagen type II in vitro. Transgenic mouse bone length measurement, histology, BrdU incorporation, metalloprotease-deficient truncation mutant, in vitro chondrocyte adhesion assay Journal of bone and mineral research High 16869727
2009 ADAM12-L co-localizes with c-Src at actin-rich peripheral structures; two separate c-Src binding sites in the ADAM12-L cytoplasmic tail interact with the SH3 domain of c-Src; c-Src kinase activity induces ADAM12-L tyrosine phosphorylation; the association is stabilized when c-Src kinase activity is disrupted; ADAM12-L enhances Src kinase activity upon integrin engagement. Co-immunoprecipitation, co-localization imaging, SH3 domain binding assay, kinase-inactive c-Src mutant, tyrosine phosphorylation Western blot Experimental cell research High 19769962
2009 MMP-7 controls transcription of ADAM12, forming a novel MMP-7/ADAM12 signaling axis in agonist-induced hypertension and cardiac hypertrophy; MMP-7 knockdown attenuates hypertension, inhibits ADAM12 overexpression, and prevents cardiac hypertrophy in mouse models. RNAi knockdown, antisense oligodeoxynucleotides, MMP-7 gene knockout, quantitative RT-PCR, rodent hypertension models Circulation Medium 19398663
2010 Antibody ligation of ADAM12 induces formation of invadopodia clusters with ECM-degrading capacity in cells expressing αvβ3 integrin and active c-Src; this requires an intact c-Src interaction site in the ADAM12 cytoplasmic domain but is independent of ADAM12 catalytic activity; caveolin-1 and MMP14/MT1-MMP localize in these clusters; ADAM12-mediated HB-EGF shedding occurs within invadopodia. Antibody ligation, invadopodia formation assay, domain mutants (cytoplasmic tail deletion, catalytic mutant), cholesterol depletion, ectodomain shedding assay Experimental cell research High 20951132
2010 TGF-β1 induces ADAM12 mRNA and protein in a Smad2/Smad3-dependent manner; SnoN, a negative regulator of TGF-β signaling, acts as a repressor of ADAM12 gene expression; SnoN overexpression reduces ADAM12 induction, while SnoN shRNA knockdown enhances it. Smad2/3-dependent reporter, shRNA knockdown of SnoN, overexpression of SnoN, Western blot, qRT-PCR The Journal of biological chemistry Medium 20457602
2010 ADAM12 selectively inhibits ADAM12 activity; engineered N-TIMP-2 (with AB-loop removed) shows increased affinity for ADAM12 compared to TACE/ADAM17; N-TIMP-2 and its mutants inhibit the transmembrane ADAM12-L in cell-based HB-EGF shedding assays, revealing distinctive structural requirements for ADAM12 inhibition. Kinetic analysis with fluorescent peptide substrate, N-TIMP-2 mutagenesis, cell-based EGF shedding assay The Biochemical journal High 20533908
2011 Notch signaling up-regulates ADAM12 expression in a CSL-dependent, IκB kinase-dependent manner; the microRNA-29 family mediates this effect by being downregulated by Notch, relieving repression of the ADAM12 3'UTR; in human cells, Notch specifically up-regulates ADAM12-L (which has a divergent 3'UTR containing the miR-29 site) but not ADAM12-S. Constitutively active Notch1 transfection, CSL reporter, IKK inhibitor, miR-29 target site validation, co-culture with Notch ligand-expressing cells, qRT-PCR The Journal of biological chemistry High 21518768
2011 Breast cancer-associated ADAM12 somatic mutations D301H and G479E (involving conserved residues) cause retention of ADAM12 in the ER, block cell surface trafficking, prevent Delta-like 1 shedding, and exert dominant-negative effects on wild-type ADAM12 processing. Mutagenesis, cell surface biotinylation, immunofluorescence, ectodomain shedding assay, dominant-negative co-expression International journal of cancer High 18241035
2013 Notch signaling increases ADAM12 metalloprotease levels and activity in hypoxia in a Notch-dependent manner, leading to increased HB-EGF shedding, EGFR activation, and invadopodia formation; thus Notch-ADAM12-HB-EGF-EGFR constitutes a hypoxia-driven invasion signaling axis. Notch pathway inhibition, ADAM12 knockdown/overexpression, ectodomain shedding assay, invadopodia formation assay The Journal of cell biology High 23589494
2013 ADAM12 redistributes endogenous MMP-14 to the cell surface and promotes its activation; subsequent gelatin degradation and reduced apoptosis depend on MMP-14 activity and cell surface αVβ3 integrin localization but not on ADAM12 catalytic activity or its cytoplasmic tail; a ternary ADAM12/αVβ3/MMP-14 complex is proposed based on co-localization and antibody inhibition. Co-localization, MMP-14 activity assays, specific monoclonal antibodies, domain mutants (catalytic-dead, cytoplasmic tail deletion), orthotopic implantation, Western blot for activated MMP-14 Journal of cell science High 24006261
2013 ADAM12 was identified by yeast two-hybrid as an EphA1-binding partner; ADAM12 enhances ephrin-A1 cleavage in response to TGF-β1 in primary tumors, releasing soluble ephrin-A1 into the serum that disrupts EphA1/ephrin-A1-mediated cell adhesion in the lungs, causing hyperpermeability and facilitating lung metastasis. Yeast two-hybrid, ectodomain cleavage assay (TGF-β1 stimulation), neutralizing antibody against soluble ephrin-A1, lung metastasis model Oncogene Medium 23686306
2013 ADAM12 screens positive for shedding of five new substrates: Kitl1, VE-cadherin, Flk-1, Tie-2, and VCAM-1; siRNA knockdown of ADAM12 reduces cytokine-induced VE-cadherin shedding in endothelial cells. Ectodomain shedding screen, siRNA knockdown, Western blot of shed forms The Biochemical journal Medium 23458101
2012 ILK (integrin-linked kinase) was identified as a new ADAM12L interacting protein; ADAM12L co-immunoprecipitates with ILK via its cytoplasmic tail; in hepatic stellate cells, ADAM12L and ILK redistribute to focal adhesions upon β1 integrin stimulation; ADAM12L upregulation activates Akt Ser-473 phosphorylation via PI3K/ILK in a protease-independent manner; ILK depletion abolishes this survival signal. Co-immunoprecipitation, siRNA knockdown of ILK and ADAM12L, cytoplasmic tail deletion mutant, Akt phosphorylation Western blot, ILK kinase activity assay from immunoprecipitates Molecular biology of the cell High 22767580
2015 ADAM12 mediates ectodomain shedding of E-cadherin to promote trophoblast fusion; siRNA knockdown of ADAM12 impedes spontaneous cytotrophoblast fusion; overexpression of ADAM12S potentiates fusion in Bewo cells; E-cadherin is identified as a novel ADAM12 substrate; ADAM12 expression is under transcriptional control of protein kinase A. siRNA knockdown, ADAM12S overexpression, E-cadherin shedding assay, PKA inhibitor, two distinct trophoblast fusion models Cell death and differentiation High 25909890
2015 ADAM12L (but not ADAM12S) induces EMT in MCF10A cells independently of proteolytic activity but requiring the cytoplasmic tail; ADAM12L-dependent EMT involves increased phosphorylation of Smad3, Akt, and ERK; TGF-β receptor or ERK inhibition reverses ADAM12L-induced mesenchymal phenotype. ADAM12L overexpression (catalytic mutant, cytoplasmic tail deletion), Western blot for EMT markers and phospho-signaling, TGF-β receptor inhibitor, ERK inhibitor PloS one High 26407179
2015 miR-29b/c and miR-200b/c directly target the ADAM12-L 3'UTR (but not ADAM12-S 3'UTR) to reduce ADAM12-L mRNA and protein levels; mutation of miR-29b/c or miR-200b/c target sequences in the ADAM12-L 3'UTR abrogates this repression; miR-30b/d did not show consistent effects. miRNA mimic transfection, 3'UTR luciferase reporter assay with target site mutations, metabolic labeling for translation rate, miRNA hairpin inhibitors, qRT-PCR BMC cancer High 25886595
2015 ADAM12 expression in endothelial cells regulates the neural vascular barrier under hypoxia by mediating shedding of claudin-5 (tight junction molecule); inhibition of ADAM12 (or ADAM17) metalloprotease activity rescues claudin-5 membrane localization and barrier function both in vitro and in vivo under hypoxia. Metalloprotease inhibition, ADAM12 and ADAM17 specific knockdown, in vitro barrier assay (TEER), in vivo neural vascular barrier assessment Scientific reports Medium 26242473
2005 ADAM12 protease activity and the FISH adapter protein mediate Aβ-induced neuronal death; expression of a protease-deficient ADAM12 mutant blocks Aβ-induced neuronal death; the C-terminal FISH fragment induces cell death that requires ADAM12 metalloprotease activity; Aβ treatment and toxic FISH fragment both induce accumulation of an ADAM12 N-terminal cleavage product, indicating ADAM12 sheddase activation. Protease-deficient ADAM12 mutant expression, FISH domain truncation expression, conditioned medium analysis for ADAM12 cleavage products, neuronal cell death assay Proceedings of the National Academy of Sciences of the United States of America Medium 15710903
2017 Twist1 transcription factor induces ADAM12 expression; ADAM12 knockdown blocks Twist1-induced tumor invasion and metastasis in breast xenografts without affecting primary tumor formation; both the disintegrin and metalloproteinase domains are required for invadopodia function, while the metalloproteinase domain is dispensable for focal adhesion turnover; ADAM12 knockdown inhibits focal adhesion turnover (shown by live-imaging). siRNA/shRNA knockdown, 3D organoid invasion assay, xenograft metastasis model, live-imaging of focal adhesion turnover, domain mutant analysis Journal of cell science High 28468988
2019 ADAM12 interacts with basigin and cleaves it in the juxtamembrane region; ADAM12 overexpression increases ectodomain shedding of an alkaline phosphatase-tagged basigin reporter; CRISPR/Cas9 knockout of ADAM12 reduces basigin shedding, which is rescued by ADAM12 re-expression; ADAM12-generated basigin ectodomain fragments were detected in conditioned media and serum samples. Co-immunoprecipitation, alkaline phosphatase shedding reporter, CRISPR/Cas9 knockout, rescue by re-expression, Western blot for endogenous ectodomain fragments in conditioned media and serum International journal of molecular sciences High 31013576
2021 Hypoxia activates HIF-dependent ADAM12 expression in breast cancer cells, which mediates increased HB-EGF ectodomain shedding, EGFR activation, and FAK phosphorylation; ADAM12 inhibition decreased hypoxia-induced cell migration/invasion in vitro and dramatically impaired lung metastasis in orthotopic mouse models. HIF knockdown/overexpression, ADAM12 siRNA, ectodomain shedding assay, EGFR/FAK phosphorylation Western blot, orthotopic breast cancer metastasis model Proceedings of the National Academy of Sciences of the United States of America High 33952697
2020 ADAM12 acts as a T-cell costimulatory molecule expressed on naïve T cells; ADAM12 Fab antibody stimulation amplifies TCR signaling to promote T-bet-mediated IFNγ production and Th1 differentiation; genomic ADAM12 loss or T-cell ADAM12 knockdown selectively diminishes T-bet and IFNγ in Th1 cells without affecting Th17 cells; ADAM12-/- mice show profoundly reduced Th1-mediated neuroinflammation in EAE. Monoclonal ADAM12 Fab antibody stimulation, ADAM12 knockout mice, shRNA knockdown in T cells, EAE model, transcriptomic profiling, IFNγ/T-bet measurement Cellular & molecular immunology High 32572163
2005 FLRG (follistatin-related gene) directly interacts with the cysteine-rich domain of ADAM12 as identified by yeast two-hybrid; FLRG inhibits osteoclast differentiation from murine spleen cells and RAW264.7 macrophages, reducing osteoclast numbers and nuclei count. Yeast two-hybrid, osteoclast differentiation assay with recombinant FLRG, RANKL/M-CSF stimulation Biology of the cell Low 15574124
2005 TGF-β induces ADAM12 gene expression through PI3K/Frap-mTOR/p70S6K and MEK/ERK pathways in hepatic stellate cells. Inhibition of p70S6K by rapamycin blocks TGF-β-dependent ADAM12 expression. Rapamycin, LY294002, UO126 treatment; p70S6K phosphorylation Western blot; TGF-β1 stimulation Journal of hepatology Medium 16139919

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a new therapy. Nature medicine 606 11786904
2012 Lineage tracing and genetic ablation of ADAM12(+) perivascular cells identify a major source of profibrotic cells during acute tissue injury. Nature medicine 344 22842476
2000 RGD-independent binding of integrin alpha9beta1 to the ADAM-12 and -15 disintegrin domains mediates cell-cell interaction. The Journal of biological chemistry 183 10944520
2003 ADAM12 in human liver cancers: TGF-beta-regulated expression in stellate cells is associated with matrix remodeling. Hepatology (Baltimore, Md.) 180 12717386
2008 Cellular roles of ADAM12 in health and disease. The international journal of biochemistry & cell biology 165 18342566
2005 The disintegrin-metalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer. International journal of oncology 147 15586220
2004 ADAM12 is selectively overexpressed in human glioblastomas and is associated with glioblastoma cell proliferation and shedding of heparin-binding epidermal growth factor. The American journal of pathology 127 15509542
2005 A role for ADAM12 in breast tumor progression and stromal cell apoptosis. Cancer research 125 15930294
2013 Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia. The Journal of cell biology 120 23589494
2007 First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system. Prenatal diagnosis 117 17278174
2003 ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function. Journal of cell science 117 12915587
2006 Molecular profiling of ADAM12 in human bladder cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 104 17189408
2005 Reduction of the disintegrin and metalloprotease ADAM12 in preeclampsia. Obstetrics and gynecology 102 15994630
2007 The disintegrin and metalloproteinase ADAM12 contributes to TGF-beta signaling through interaction with the type II receptor. The Journal of cell biology 100 17620406
2002 ADAM12/syndecan-4 signaling promotes beta 1 integrin-dependent cell spreading through protein kinase Calpha and RhoA. The Journal of biological chemistry 100 12509413
1998 Spatially- and temporally-restricted expression of meltrin alpha (ADAM12) and beta (ADAM19) in mouse embryo. Mechanisms of development 90 9622634
2006 ADAM12 is highly expressed in carcinoma-associated stroma and is required for mouse prostate tumor progression. Oncogene 86 16607276
2003 ADAM12: a novel first-trimester maternal serum marker for Down syndrome. Prenatal diagnosis 86 14691998
2004 ADAM12 and alpha9beta1 integrin are instrumental in human myogenic cell differentiation. Molecular biology of the cell 77 15574885
2021 Hypoxia-inducible factor-dependent ADAM12 expression mediates breast cancer invasion and metastasis. Proceedings of the National Academy of Sciences of the United States of America 76 33952697
2003 PACSIN3 binds ADAM12/meltrin alpha and up-regulates ectodomain shedding of heparin-binding epidermal growth factor-like growth factor. The Journal of biological chemistry 74 12952982
2009 Matrix metalloproteinase-7 and ADAM-12 (a disintegrin and metalloproteinase-12) define a signaling axis in agonist-induced hypertension and cardiac hypertrophy. Circulation 66 19398663
2018 Adam12 and lnc015192 act as ceRNAs in breast cancer by regulating miR-34a. Oncogene 63 30042416
2013 ADAM12-cleaved ephrin-A1 contributes to lung metastasis. Oncogene 62 23686306
2017 ADAM12 induces EMT and promotes cell migration, invasion and proliferation in pituitary adenomas via EGFR/ERK signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 61 29136943
2004 Regulation of ADAM12 cell-surface expression by protein kinase C epsilon. The Journal of biological chemistry 61 15364951
2011 ADAM12 transmembrane and secreted isoforms promote breast tumor growth: a distinct role for ADAM12-S protein in tumor metastasis. The Journal of biological chemistry 58 21493715
2008 First-trimester maternal serum a disintegrin and metalloprotease 12 (ADAM12) and adverse pregnancy outcome. Obstetrics and gynecology 57 18978109
2013 A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications. Biochimica et biophysica acta 55 23680494
2002 Intracellular processing of metalloprotease disintegrin ADAM12. The Journal of biological chemistry 53 12000744
2013 ADAM12 redistributes and activates MMP-14, resulting in gelatin degradation, reduced apoptosis and increased tumor growth. Journal of cell science 52 24006261
2007 Catalytic properties of ADAM12 and its domain deletion mutants. Biochemistry 52 18081311
2005 Involvement of the serine/threonine p70S6 kinase in TGF-beta1-induced ADAM12 expression in cultured human hepatic stellate cells. Journal of hepatology 52 16139919
2003 Role of metalloprotease disintegrin ADAM12 in determination of quiescent reserve cells during myogenic differentiation in vitro. Molecular and cellular biology 52 12972593
2006 ADAM12 is a four-leafed clover: the excised prodomain remains bound to the mature enzyme. The Journal of biological chemistry 51 16455653
2015 ADAM12-directed ectodomain shedding of E-cadherin potentiates trophoblast fusion. Cell death and differentiation 50 25909890
2017 Metalloprotease-disintegrin ADAM12 actively promotes the stem cell-like phenotype in claudin-low breast cancer. Molecular cancer 49 28148288
2008 First trimester maternal serum PAPP-A, beta-hCG and ADAM12 in prediction of small-for-gestational-age fetuses. Prenatal diagnosis 49 19003798
2013 ADAM12 is expressed in the tumour vasculature and mediates ectodomain shedding of several membrane-anchored endothelial proteins. The Biochemical journal 47 23458101
2013 Polymorphic variation within the ADAMTS2, ADAMTS14, ADAMTS5, ADAM12 and TIMP2 genes and the risk of Achilles tendon pathology: a genetic association study. Journal of science and medicine in sport 47 23491141
2017 ADAM12 Is a Novel Regulator of Tumor Angiogenesis via STAT3 Signaling. Molecular cancer research : MCR 46 28765266
2016 Perivascular Cells in Diffuse Cutaneous Systemic Sclerosis Overexpress Activated ADAM12 and Are Involved in Myofibroblast Transdifferentiation and Development of Fibrosis. The Journal of rheumatology 46 27252423
2015 Urinary ADAM12 and MMP-9/NGAL complex detect the presence of gastric cancer. Cancer prevention research (Philadelphia, Pa.) 46 25591790
2018 ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy. Oncogenesis 45 30442938
2008 RACK1, a new ADAM12 interacting protein. Contribution to liver fibrogenesis. The Journal of biological chemistry 43 18621736
2020 ADAM12 is A Potential Therapeutic Target Regulated by Hypomethylation in Triple-Negative Breast Cancer. International journal of molecular sciences 42 32019179
2017 ADAM12 induction by Twist1 promotes tumor invasion and metastasis via regulation of invadopodia and focal adhesions. Journal of cell science 42 28468988
2015 The Disintegrin and Metalloprotease ADAM12 Is Associated with TGF-β-Induced Epithelial to Mesenchymal Transition. PloS one 42 26407179
2011 ADAM12 produced by tumor cells rather than stromal cells accelerates breast tumor progression. Molecular cancer research : MCR 42 21875931
2008 ADAM12: a potential target for the treatment of chronic wounds. Journal of molecular medicine (Berlin, Germany) 42 18604515
2012 Epigenetic regulation by Z-DNA silencer function controls cancer-associated ADAM-12 expression in breast cancer: cross-talk between MeCP2 and NF1 transcription factor family. Cancer research 41 23135915
2011 A positive feedback loop between HER2 and ADAM12 in human head and neck cancer cells increases migration and invasion. Oncogene 41 21986939
2005 Amyloid-beta neurotoxicity is mediated by FISH adapter protein and ADAM12 metalloprotease activity. Proceedings of the National Academy of Sciences of the United States of America 40 15710903
2006 ADAM12-S stimulates bone growth in transgenic mice by modulating chondrocyte proliferation and maturation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 38 16869727
2016 Metalloproteinases ADAM12 and MMP-14 are associated with cavernous sinus invasion in pituitary adenomas. International journal of cancer 37 27144841
2015 ADAM12-L is a direct target of the miR-29 and miR-200 families in breast cancer. BMC cancer 37 25886595
2009 Targeting ADAM12 in human disease: head, body or tail? Current pharmaceutical design 37 19601832
2018 An ADAM12 and FAK positive feedback loop amplifies the interaction signal of tumor cells with extracellular matrix to promote esophageal cancer metastasis. Cancer letters 36 29476791
2015 ADAM12: a genetic modifier of preclinical peripheral arterial disease. American journal of physiology. Heart and circulatory physiology 36 26163448
2012 Genetic association analysis of GDF5 and ADAM12 for knee osteoarthritis. Joint bone spine 36 22284607
2010 Selective inhibition of ADAM12 catalytic activity through engineering of tissue inhibitor of metalloproteinase 2 (TIMP-2). The Biochemical journal 35 20533908
2010 Extracellular engagement of ADAM12 induces clusters of invadopodia with localized ectodomain shedding activity. Experimental cell research 35 20951132
2008 Heparan sulfate regulates ADAM12 through a molecular switch mechanism. The Journal of biological chemistry 35 18801731
2011 Metalloprotease-disintegrin ADAM12 expression is regulated by Notch signaling via microRNA-29. The Journal of biological chemistry 34 21518768
2009 ADAM12 localizes with c-Src to actin-rich structures at the cell periphery and regulates Src kinase activity. Experimental cell research 33 19769962
2004 Interaction of the disintegrin and cysteine-rich domains of ADAM12 with integrin alpha7beta1. Experimental cell research 33 15242759
2013 A disintegrin and metalloproteinase 12 (ADAM12) localizes to invasive trophoblast, promotes cell invasion and directs column outgrowth in early placental development. Molecular human reproduction 32 24243624
2010 ADAM12 is expressed by astrocytes during experimental demyelination. Brain research 30 20176000
2010 The role of SnoN in transforming growth factor beta1-induced expression of metalloprotease-disintegrin ADAM12. The Journal of biological chemistry 30 20457602
2008 The metalloproteinase ADAM-12 regulates bronchial epithelial cell proliferation and apoptosis. Cell proliferation 30 19040574
2014 Extravillous trophoblast-associated ADAM12 exerts pro-invasive properties, including induction of integrin beta 1-mediated cellular spreading. Biology of reproduction 29 24695627
2011 ADAM12 induces estrogen-independence in breast cancer cells. Breast cancer research and treatment 29 21387162
2007 Transgenic overexpression of ADAM12 suppresses muscle regeneration and aggravates dystrophy in aged mdx mice. The American journal of pathology 29 17982130
2002 The expression of ADAM12 (meltrin alpha) in human giant cell tumours of bone. Molecular pathology : MP 29 12456779
2008 Breast cancer-associated mutations in metalloprotease disintegrin ADAM12 interfere with the intracellular trafficking and processing of the protein. International journal of cancer 28 18241035
2005 Hierarchy of ADAM12 binding to integrins in tumor cells. Experimental cell research 28 16061220
2023 ADAM12 promotes clear cell renal cell carcinoma progression and triggers EMT via EGFR/ERK signaling pathway. Journal of translational medicine 27 36717944
2009 Metal-proteinase ADAM12, kinesin 14 and checkpoint suppressor 1 as new molecular markers of laryngeal carcinoma. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 27 19609547
2015 ADAM12 and ADAM17 are essential molecules for hypoxia-induced impairment of neural vascular barrier function. Scientific reports 25 26242473
2013 The ADAM12 is upregulated in synovitis and postinflammatory fibrosis of the synovial membrane in patients with early radiographic osteoarthritis. Joint bone spine 25 23578941
2013 Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity. Cancer medicine 25 24402778
2011 The secretion of PAPP-A, ADAM12, and PP13 correlates with the size of the placenta for the first month of pregnancy. Placenta 24 22015022
2015 Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain. Scientific reports 23 26477568
2013 Metalloproteinase-disintegrin ADAM12 is associated with a breast tumor-initiating cell phenotype. Breast cancer research and treatment 23 23771733
2007 Interaction between the ADAM12 and SH3MD1 genes may confer susceptibility to late-onset Alzheimer's disease. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 23 17440933
2005 ADAM12-mediated focal adhesion formation is differently regulated by beta1 and beta3 integrins. FEBS letters 23 16213489
2012 Identification of ILK as a new partner of the ADAM12 disintegrin and metalloprotease in cell adhesion and survival. Molecular biology of the cell 22 22767580
2005 FLRG, a new ADAM12-associated protein, modulates osteoclast differentiation. Biology of the cell 22 15574124
2020 ADAM12 is a costimulatory molecule that determines Th1 cell fate and mediates tissue inflammation. Cellular & molecular immunology 21 32572163
2019 Identification of ADAM12 as a Novel Basigin Sheddase. International journal of molecular sciences 21 31013576
2014 EMMPRIN and ADAM12 in prostate cancer: preliminary results of a prospective study. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21 25139103
2012 Serum levels of ADAM12-S: possible association with the initiation and progression of dermal fibrosis and interstitial lung disease in patients with systemic sclerosis. Journal of the European Academy of Dermatology and Venereology : JEADV 21 22540429
2012 First-trimester prediction of preterm birth using ADAM12, PAPP-A, uterine artery Doppler, and maternal characteristics. Prenatal diagnosis 21 22847849
2015 ADAM12 and PAPP-A: Candidate regulators of trophoblast invasion and first trimester markers of healthy trophoblasts. Cell adhesion & migration 20 26417939
2017 ADAM12-L confers acquired 5-fluorouracil resistance in breast cancer cells. Scientific reports 19 28852196
2015 Expression of ADAM12 is regulated by E2F1 in small cell lung cancer. Oncology reports 18 26503019
2017 Upregulation of ADAM12 contributes to accelerated cell proliferation and cell adhesion-mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphoma. Hematology (Amsterdam, Netherlands) 17 28395594
2012 Upregulated expression of ADAM12 is associated with progression of oral squamous cell carcinoma. International journal of oncology 17 22267082
2009 Adam12 plays a role during uterine decidualization in mice. Cell and tissue research 17 19841944
2005 Cooperation of the metalloprotease, disintegrin, and cysteine-rich domains of ADAM12 during inhibition of myogenic differentiation. The Journal of biological chemistry 17 15849365

Missed literature

Know a paper Affinage missed for ADAM12? Flag it for the maintainers and the community.

No submissions yet.