Affinage

ADAM28

Disintegrin and metalloproteinase domain-containing protein 28 · UniProt Q9UKQ2

Round 2 corrected
Length
775 aa
Mass
87.1 kDa
Annotated
2026-04-28
126 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADAM28 is a catalytically active disintegrin metalloproteinase that processes multiple extracellular substrates—including IGFBP-3, VWF, CTGF, CD23, CD200, Notch2, TNF-α, C1q, and myelin basic protein—to regulate IGF-I bioavailability, cancer cell survival, VEGF165 release, complement-mediated cell death, and leukocyte adhesion (PMID:11389903, PMID:15013428, PMID:20971063, PMID:22636800, PMID:26918856, PMID:12777399, PMID:23010875, PMID:28707394). ADAM28 undergoes autocatalytic pro-domain removal in a late Golgi compartment and can be further activated by MMP-7; its metalloproteinase activity is inhibited by TIMP-3 and TIMP-4 but not TIMP-1 or TIMP-2 (PMID:10794709, PMID:15013428, PMID:11389903). Its disintegrin domain independently mediates binding to integrin α4β1 on leukocytes and to PSGL-1, promoting lymphocyte adhesion to VCAM-1, transendothelial migration, and P-selectin-dependent leukocyte recruitment during inflammation (PMID:11724793, PMID:12667064, PMID:17597069, PMID:21332445). Src kinase drives ADAM28 transcription through MEK/ERK and PI3K/mTOR signaling in carcinoma cells, and the ADAM28 locus is epigenetically silenced by EBV EBNA3C via KDM2B-mediated H3K4me3 removal and Polycomb-dependent H3K27me3 deposition (PMID:24007880, PMID:30135119).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 Low

    Cloning of ADAM28 from epididymis revealed a reprolysin-like catalytic consensus, predicting it to be a catalytically active ADAM—setting the stage for functional enzymology.

    Evidence cDNA cloning and sequence analysis from human and macaque epididymis

    PMID:10587367

    Open questions at the time
    • Sequence prediction only; no enzymatic activity demonstrated
    • Expression restricted to one tissue at this stage
  2. 2000 High

    Demonstration that ADAM28 pro-domain removal is autocatalytic (not furin-dependent) in a late Golgi compartment established a unique activation mechanism among ADAMs.

    Evidence Catalytic-site Glu→Ala mutagenesis in COS-7 cells with surface trypsinization and subcellular fractionation

    PMID:10794709

    Open questions at the time
    • Whether additional proteases contribute to activation in vivo
    • Exact Golgi sub-compartment not determined
  3. 2001 High

    Two key properties were established: ADAM28 is a zinc metalloproteinase capable of cleaving myelin basic protein and is insensitive to TIMP-1/TIMP-2, while its disintegrin domain binds integrin α4β1 in a divalent-cation-dependent manner—distinguishing its catalytic and adhesive functions.

    Evidence In vitro cleavage assays with mutagenesis (catalytic activity) and Fc-fusion adhesion assays with function-blocking antibodies on transfected K562 cells (integrin binding)

    PMID:11389903 PMID:11724793

    Open questions at the time
    • Physiological relevance of MBP cleavage unclear
    • Other integrin partners not yet surveyed
  4. 2003 High

    Mapping of the α4β1-binding interface on the disintegrin domain to seven specific residues extending beyond the classical RGD loop, and identification of CD23 as a catalytic substrate, separated the structural determinants of adhesion from those of proteolysis.

    Evidence Charge-to-alanine mutagenesis with Jurkat adhesion assay (binding); synthetic peptide library screening and ectodomain shedding assay (CD23 cleavage)

    PMID:12667064 PMID:12777399

    Open questions at the time
    • No crystal structure of the disintegrin domain
    • Relative contribution of ADAM28 vs. ADAM10/ADAM17 to CD23 shedding in vivo
  5. 2004 High

    Discovery that MMP-7 activates secreted proADAM28s and that the active enzyme cleaves IGFBP-3 (inhibitable by TIMP-3/TIMP-4) established a proteolytic cascade linking extracellular matrix remodeling to IGF-I signaling.

    Evidence In vitro reconstitution of MMP-7-mediated activation, IGFBP-3 cleavage assay with metalloprotease inhibitor panel

    PMID:15013428

    Open questions at the time
    • In vivo MMP-7-dependent activation not yet shown
    • Whether other MMPs also activate proADAM28
  6. 2006 High

    ADAM28-mediated IGFBP-3 cleavage was shown to have direct cancer relevance: siRNA knockdown in breast carcinoma cells reduced IGF-I signaling, proliferation, and xenograft tumor growth, placing ADAM28 as a pro-tumorigenic protease.

    Evidence siRNA knockdown and anti-ADAM28 antibody in MDA-MB231 cells with IGFBP-3 cleavage, IGF-I signaling readout, and xenograft model

    PMID:17047053

    Open questions at the time
    • Contribution of other IGFBP-3-degrading proteases in tumors
    • Human clinical validation absent
  7. 2007 High

    Identification of PSGL-1 as a disintegrin domain binding partner that enhances P-selectin-mediated leukocyte adhesion and pulmonary accumulation demonstrated ADAM28's non-catalytic role in inflammation.

    Evidence Yeast two-hybrid confirmed by co-IP, domain binding assays, and in vivo endotoxin inflammation model

    PMID:17597069

    Open questions at the time
    • Whether ADAM28 also cleaves PSGL-1
    • Relative importance in neutrophil vs. lymphocyte recruitment
  8. 2010 High

    Discovery that ADAM28 cleaves CTGF at defined bonds to liberate VEGF165 from the CTGF/VEGF complex connected ADAM28 to angiogenic signaling.

    Evidence Yeast two-hybrid, protein binding assay, in vitro cleavage with bond identification, VEGF165 release measurement

    PMID:20971063

    Open questions at the time
    • In vivo angiogenesis readout not performed
    • Whether ADAM28-released VEGF165 is sufficient to drive neovascularization
  9. 2012 High

    Two new substrates—VWF and TNF-α—were identified: ADAM28-mediated VWF cleavage protects carcinoma cells from VWF-induced apoptosis during hematogenous metastasis, and ADAM28 contributes to TNF-α ectodomain shedding in macrophages.

    Evidence VWF: yeast two-hybrid, cleavage assay, shRNA/siRNA, neutralizing antibody, xenograft metastasis model; TNF-α: co-IP, ELISA, siRNA in THP-1 cells

    PMID:22636800 PMID:23010875

    Open questions at the time
    • Relative contribution of ADAM28 vs. ADAM17 (TACE) to TNF-α shedding
    • VWF cleavage site not identified
  10. 2013 High

    Src kinase was identified as a transcriptional inducer of ADAM28 through MEK/ERK and PI3K/mTOR, explaining ADAM28 upregulation in carcinomas and providing a signaling link to oncogenic transformation.

    Evidence Kinase inhibitors in v-src-transformed MDCK cells and human carcinoma lines, RT-PCR, IHC tissue correlation, in vivo anti-ADAM28 antibody tumor suppression

    PMID:24007880

    Open questions at the time
    • Direct transcription factor(s) binding the ADAM28 promoter not identified
    • Whether Src-independent mechanisms maintain ADAM28 in non-transformed cells
  11. 2016 High

    Identification of C1q as a physiological ADAM28 substrate in normal epithelia revealed a cytoprotective function: ADAM28 cleavage of C1q attenuates complement-driven apoptosis and autophagy, defining a homeostatic role beyond cancer.

    Evidence Yeast two-hybrid, co-IP, SPR, siRNA knockdown, recombinant ADAM28 pre-treatment with apoptosis/autophagy assays in bronchial epithelial cells

    PMID:26918856

    Open questions at the time
    • Whether C1q cleavage modulates classical complement activation in vivo
    • Cleavage site in C1q not mapped
  12. 2017 Medium

    ADAM28 was linked to Notch2 signaling in B-cell differentiation (MZP→MZ B cells via CD19/Foxo1) and to trophoblast invasion in early placenta, broadening its physiological roles beyond immunity and cancer.

    Evidence CD19-KO mice with Notch2 cleavage assay (B cells); siRNA in placental explant cultures with apoptosis readout (trophoblast)

    PMID:28623976 PMID:28707394

    Open questions at the time
    • Whether ADAM28 directly cleaves Notch2 or acts indirectly
    • Redundancy with other Notch-processing ADAMs (ADAM10/17) in MZ B-cell fate
  13. 2018 High

    Epigenetic silencing of the ADAM28 locus by EBV EBNA3C was mechanistically dissected into two pathways—KDM2B-mediated H3K4me3 removal and Polycomb-dependent H3K27me3 deposition—explaining ADAM28 downregulation in EBV-transformed B cells.

    Evidence Recombinant EBV with EBNA3C mutations, ChIP for H3K4me3, H3K27me3, KDM2B, BMI1, SUZ12

    PMID:30135119

    Open questions at the time
    • Functional consequence of ADAM28 silencing for EBV latency
    • Whether EBNA3C-dependent silencing is reversible in vivo
  14. 2022 Medium

    Multiple studies placed ADAM28 downstream of miRNA/lncRNA regulatory circuits (miR-198, miR-128-3p/NEAT1) and upstream of JAK2/STAT3 signaling, linking ADAM28 to autophagy and apoptosis regulation in solid tumors.

    Evidence Dual-luciferase reporter assays for miRNA–3′-UTR binding, Western blot for p-JAK2/p-STAT3/autophagy markers, siRNA/overexpression with in vivo xenograft

    PMID:30840270 PMID:36054559

    Open questions at the time
    • Mechanism by which ADAM28 activates JAK2/STAT3 is unknown
    • Whether the effect is substrate-cleavage-dependent or disintegrin-mediated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the transcription factor(s) directly driving ADAM28 promoter activity downstream of Src/MEK/ERK, the structural basis of substrate recognition (no crystal structure exists), the mechanism linking ADAM28 to JAK/STAT activation, and the relative physiological contribution of ADAM28 vs. ADAM10/ADAM17 in Notch2 and TNF-α processing in vivo.
  • No crystal or cryo-EM structure of any ADAM28 domain
  • Direct ADAM28-Notch2 cleavage assay lacking
  • In vivo ADAM28 knockout phenotype in mammals not reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016787 hydrolase activity 5 GO:0098631 cell adhesion mediator activity 4
Localization
GO:0005576 extracellular region 4 GO:0005886 plasma membrane 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 2 R-HSA-392499 Metabolism of proteins 2
Partners
C1QACTGFIGFBP3ITGA4ITGB1SELPLGTNFVWF

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 ADAM28 is synthesized as a precursor and processed to a mature form in a late Golgi compartment; mature ADAM28 localizes to the cell surface. A glutamate-to-alanine mutation in the catalytic site abolishes pro-domain removal even though the mutant is still transported to the cell surface, indicating that pro-domain removal is at least in part autocatalytic—distinct from other ADAMs that rely on furin-like proprotein convertases. COS-7 cell expression, cell-surface trypsinization, site-directed mutagenesis (catalytic-site Glu→Ala) The Biochemical journal High 10794709
2001 Recombinant ADAM28 cleaves myelin basic protein at two defined sites; catalytic activity requires an intact catalytic-site glutamate (abolished by point mutation) and is insensitive to TIMP-1 and TIMP-2. In vitro cleavage assay with recombinant protein, site-directed mutagenesis FEBS letters High 11389903
2001 The disintegrin domain of ADAM28 (MDC-L) binds the leukocyte integrin α4β1; a 59-residue fragment of the disintegrin domain supports integrin-dependent cell adhesion in a divalent-cation-dependent, function-blocking-antibody-inhibitable manner. Binding requires activation of β1 integrins. Recombinant Fc fusion protein adhesion assay, α4/β1 function-blocking mAbs, transfected K562 cells expressing α4β1 The Journal of biological chemistry High 11724793
2003 Seven specific residues (Lys437, Lys442, Lys455, Lys459, Lys460, Lys469, Glu476) in the ADAM28 disintegrin domain are essential for α4β1-dependent cell adhesion, and molecular modelling places these residues on one face of the domain, extending beyond the classical disintegrin loop. Charge-to-alanine mutagenesis of recombinant disintegrin domain, Jurkat cell adhesion assay Biochemistry High 12667064
2003 ADAM28 (MDC-L) catalyzes ectodomain shedding of CD23 (the low-affinity IgE receptor) in vitro; this activity requires a catalytically intact enzyme and is distinct from the substrate specificity of ADAM17, as shown by synthetic peptide library screening. Synthetic peptide substrate library screening, ectodomain shedding assay with soluble recombinant enzyme, hydroxamic acid metalloprotease inhibitor The Journal of biological chemistry High 12777399
2004 ProADAM28s (65 kDa secreted form) is activated by MMP-7 (matrilysin-1), which cleaves the propeptide to yield 42- and 40-kDa active forms. Activated ADAM28s cleaves IGFBP-3 in both free and IGF-I/IGF-II-complexed forms; cleavage is blocked by EDTA, 1,10-phenanthroline, KB-R7785, TIMP-3, and TIMP-4. In vitro activation assay (recombinant MMP-7 + proADAM28s), immunoblotting, metalloprotease inhibitors Biochemical and biophysical research communications High 15013428
2005 Mouse ADAM28 is expressed in an epididymal region-specific manner regulated by testicular factors (not androgen); unlike ADAM7, ADAM28 is not transferred to the sperm surface, indicating distinct functional roles of these two epididymal ADAMs. Region-specific RT-PCR, castration/hormone replacement experiments, protein analysis of sperm fractions Biochemical and biophysical research communications Medium 15883027
2006 ADAM28 cleaves IGFBP-3 to enhance IGF-I bioavailability and stimulate breast carcinoma cell proliferation; siRNA knockdown of ADAM28 in MDA-MB231 cells significantly reduces IGFBP-3 cleavage, IGF-I signaling, cell proliferation, and xenograft growth. siRNA knockdown, anti-ADAM28 antibody inhibition, IGFBP-3 cleavage assay, xenograft mouse model, IGF-I signaling readout Cancer research High 17047053
2007 The disintegrin-like domain of secreted ADAM28 (ADAM28s) binds PSGL-1 on leukocytes; this interaction enhances P-selectin-mediated leukocyte adhesion to endothelial cells and increases leukocyte accumulation in pulmonary microcirculation in an endotoxin inflammation mouse model. Yeast two-hybrid screen, domain-specific recombinant protein binding assays, co-immunoprecipitation, adhesion assay to P-selectin-coated wells, in vivo mouse model of endotoxin inflammation The Journal of biological chemistry High 17597069
2009 All-trans retinoic acid (ATRA) specifically induces ADAM28 expression in human chondrocytes; ADAM28 overexpression augments proteoglycan release from cartilage, whereas a disintegrin-domain-deleted mutant lacks this activity, demonstrating the disintegrin domain is required for substrate recognition/localization in cartilage degradation. ATRA stimulation of HCS-2/8 chondrosarcoma cells, ADAM28 transfection (full-length and disintegrin-deletion mutant), proteoglycan release assay Biochemical and biophysical research communications Medium 19527685
2010 ADAM28 cleaves CTGF at Ala181–Tyr182 and Asp191–Pro192 in the hinge region; this digestion releases biologically active VEGF165 from the CTGF/VEGF165 complex. CTGF was identified as a binding partner of proADAM28 by yeast two-hybrid and confirmed by protein binding assay. Yeast two-hybrid screen, protein binding assay, in vitro cleavage assay with bond identification, VEGF165 release assay Biochemical and biophysical research communications High 20971063
2011 ADAM28 binding to α4β1 is typical of integrin-ligand interactions (attenuated by anti-α4β1 antibodies, enhanced by Mn2+ and mAb 9EG7); soluble ADAM28 unexpectedly enhances α4β1-dependent cell adhesion to VCAM-1 and promotes lymphocyte transendothelial migration. Affymetrix microarray, RT-PCR, immunohistochemistry, L1-2 cell adhesion assay, transendothelial migration assay, integrin activating/blocking antibodies Cell biology international Medium 21332445
2012 ADAM28 binds and cleaves von Willebrand factor (VWF); carcinoma cells with high ADAM28 expression are resistant to VWF-induced apoptosis, while knockdown of ADAM28 increases apoptosis in lung blood vessels and significantly reduces lung metastasis in xenograft models. VWF was identified as an ADAM28-binding protein by yeast two-hybrid. Yeast two-hybrid screen, protein binding assay, immunoblotting for VWF cleavage, shRNA/siRNA knockdown, anti-ADAM28 neutralizing antibody, xenograft mouse model with in vivo imaging Journal of the National Cancer Institute High 22636800
2012 ADAM28 overexpression in HEK293 cells causes co-localization and co-immunoprecipitation with TNF-α and promotes TNF-α ectodomain shedding; shedding is reduced by siRNA knockdown or pharmacological inhibition of ADAM28. Endogenous ADAM28 in THP-1 macrophages similarly mediates TNF-α shedding. Co-transfection overexpression, co-immunoprecipitation, ELISA for shed TNF-α, siRNA knockdown, pharmacological inhibition Immunology and cell biology High 23010875
2013 ADAM28 mediates ectodomain shedding of CD200 from B-CLL cells; siRNA knockdown of ADAM28 decreases sCD200 release into culture, and transfection of ADAM28 into CD200+ cells enhances sCD200 shedding. siRNA knockdown, ADAM28 gene transfection, measurement of sCD200 by ELISA Leukemia research Medium 23643150
2013 Src kinase induces ADAM28 gene expression through the MEK/ERK and PI3K/mTOR pathways in v-src-transformed epithelial cells and human carcinoma cell lines; combined inhibition of MEK and PI3K abrogates ADAM28 expression, and Src phosphorylation correlates with ADAM28 co-expression in human tumor tissues. Oncogene-transformed MDCK cells, kinase inhibitors (Src, MEK, PI3K, mTOR), RT-PCR, immunoblotting, IHC of human tumor tissues, in vivo tumor suppression by anti-ADAM28 antibody The American journal of pathology High 24007880
2016 ADAM28 is expressed in normal epithelial cells (epididymis, bronchus, stomach) where it binds and cleaves C1q; ADAM28 cleavage of C1q attenuates C1q-induced apoptosis (via p38/caspase-3) and cell death with autophagy (via LC3-II/autophagosome accumulation) in bronchial epithelial cells. C1q was identified as an ADAM28-binding protein by yeast two-hybrid and confirmed by binding assay, immunoprecipitation, and surface plasmon resonance. Yeast two-hybrid, protein binding assay, co-immunoprecipitation, surface plasmon resonance, siRNA knockdown, recombinant ADAM28 pre-treatment, apoptosis/autophagy assays The FEBS journal High 26918856
2017 CD19 controls differentiation of marginal zone precursor (MZP) cells to MZ B cells by suppressing Foxo1, which in turn upregulates ADAM28 expression; ADAM28 mediates cleavage of Notch2, enabling MZP-to-MZ B cell differentiation. CD19-deficient mice, CD19 rescue transfection, Notch2 cleavage assay, ADAM28 expression analysis in MZP cells Journal of cellular and molecular medicine Medium 28707394
2017 ADAM28 localizes to HLA-G+ distal column trophoblasts in first-trimester placenta; siRNA-mediated loss of ADAM28 impairs trophoblast column outgrowth and increases apoptosis in matrix-invading trophoblasts in placental explant cultures. qPCR, immunofluorescence microscopy, siRNA knockdown in Matrigel-embedded placental explant cultures, apoptosis assay Placenta Medium 28623976
2018 ADAM28 promotes AML leukemic cell proliferation, migration, and invasion through IGFBP-3 degradation and enhanced IGF-I-induced proliferation; ADAM28 knockout in HL-60 cells reduces growth and dissemination in xenotransplantation mouse models. ADAM28 overexpression/knockdown/knockout, IGFBP-3 cleavage assay, IGF-I stimulation, xenotransplantation mouse model Cancer letters Medium 30429106
2018 Anti-ADAM28 neutralizing antibody 211-14 (KD = 94.7 pmol/L) binds the junctional region between the cysteine-rich domain and the secreted-specific domain of ADAM28s; it inhibits IGF-1-stimulated proliferation and promotes VWF-induced cell death in lung adenocarcinoma cells, and reduces tumor growth and metastasis in lung metastasis mouse models. Antibody epitope mapping, IC50 determination, KD measurement, cell proliferation assay, VWF-induced cell death assay, mouse lung metastasis model Molecular cancer therapeutics High 30190423
2018 EBNA3C (Epstein-Barr virus) represses the ADAM28-ADAMDEC1 locus in transformed B cells by interacting with the histone lysine demethylase KDM2B, which removes the activating H3K4me3 mark; EBNA3C also recruits Polycomb proteins to deposit repressive H3K27me3, demonstrating two distinct epigenetic mechanisms of ADAM28 locus silencing. Recombinant EBV with EBNA3C RBPJ-interaction motif mutations, gene expression analysis, chromatin immunoprecipitation (ChIP) for H3K27me3, H3K4me3, BMI1, SUZ12, KDM2B Journal of virology High 30135119
2019 miR-198 directly targets the ADAM28 3'-UTR to suppress ADAM28 expression, and overexpression of ADAM28 blocks JAK/STAT pathway activation, linking ADAM28 to JAK-STAT signaling in colorectal cancer cells. Luciferase reporter assay (miR-198 binding to ADAM28 3'-UTR), Western blot for JAK/STAT proteins, ADAM28 rescue overexpression European review for medical and pharmacological sciences Medium 30840270
2021 ADAM28 from both gastric cancer cells and vascular endothelial cells (HUVECs) cleaves VWF, preventing VWF-induced apoptosis of gastric cancer cells; knockdown of ADAM28 in HUVECs increases VWF in conditioned medium and raises integrin β3, p-TP53 and cleaved caspase-3 in co-cultured gastric cancer cells. ADAM28 overexpression/knockdown, co-culture system, ELISA for VWF, Western blot for apoptosis markers, MTT/wound healing/flow cytometry assays European journal of pharmacology Medium 33675784
2022 NEAT1 lncRNA sponges miR-128-3p to upregulate ADAM28 expression; ADAM28 activates JAK2/STAT3 signaling (as shown by increased phospho-JAK2/STAT3), promoting autophagy and suppressing apoptosis in NSCLC cells; miR-128-3p overexpression-induced apoptosis is rescued by ADAM28 re-expression. Dual-luciferase reporter assay (NEAT1-miR-128-3p and miR-128-3p-ADAM28 3'-UTR), Western blot for p-JAK2/p-STAT3/autophagy proteins, siRNA/overexpression, in vivo xenograft The Kaohsiung journal of medical sciences Medium 36054559
2023 ADAM28 promotes M1 macrophage polarization in non-eosinophilic chronic rhinosinusitis with nasal polyps; ADAM28 knockdown in THP-1 macrophages reduces M1 marker expression and, via conditioned medium experiments, decreases EMT (restores E-cadherin, reduces α-SMA) and improves tight junction protein expression in nasal epithelial cells. siRNA knockdown in THP-1 macrophages, M1 polarization markers (Western blot), conditioned medium transfer to HNEPC/pHNECs, EMT and tight junction protein assays International immunopharmacology Medium 39954661
1999 ADAM28 (eMDC II) in human and macaque epididymis contains the extended catalytic-centre consensus sequence of a reprolysin-like metalloproteinase, placing it among the catalytically active ADAMs expressed in the male reproductive tract. cDNA cloning, sequence determination, Northern blot analysis Molecular human reproduction Low 10587367

Source papers

Stage 0 corpus · 126 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2010 Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 1451 20881960
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2003 Catalytic activity of ADAM8, ADAM15, and MDC-L (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23. The Journal of biological chemistry 147 12777399
2000 Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. Proceedings of the National Academy of Sciences of the United States of America 135 10737800
2006 ADAM28 is overexpressed in human breast carcinomas: implications for carcinoma cell proliferation through cleavage of insulin-like growth factor binding protein-3. Cancer research 106 17047053
2000 Cloning and characterization of ADAM28: evidence for autocatalytic pro-domain removal and for cell surface localization of mature ADAM28. The Biochemical journal 99 10794709
2004 ADAM28 is activated by MMP-7 (matrilysin-1) and cleaves insulin-like growth factor binding protein-3. Biochemical and biophysical research communications 95 15013428
2008 LGI1 and LGI4 bind to ADAM22, ADAM23 and ADAM11. International journal of biological sciences 94 18974846
2012 Effect of ADAM28 on carcinoma cell metastasis by cleavage of von Willebrand factor. Journal of the National Cancer Institute 79 22636800
2009 LGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology. Molecular and cellular neurosciences 77 19796686
2006 ADAM28 is overexpressed in human non-small cell lung carcinomas and correlates with cell proliferation and lymph node metastasis. International journal of cancer 76 16052521
2007 Methylation profile of genes CDKN2A (p14 and p16), DAPK1, CDH1, and ADAM23 in head and neck cancer. Cancer genetics and cytogenetics 70 17284367
2001 The lymphocyte metalloprotease MDC-L (ADAM 28) is a ligand for the integrin alpha4beta1. The Journal of biological chemistry 70 11724793
2018 Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy. Proceedings of the National Academy of Sciences of the United States of America 59 29987050
2005 ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric cancers by homozygous deletion or aberrant promoter hypermethylation. Oncogene 59 16103878
1999 MDC-L, a novel metalloprotease disintegrin cysteine-rich protein family member expressed by human lymphocytes. The Journal of biological chemistry 58 10506182
2001 Catalytic activity of ADAM28. FEBS letters 57 11389903
1999 Cloning and chromosomal mapping of mouse ADAM11, ADAM22 and ADAM23. Gene 55 10433968
2021 CircRNA_100565 contributes to cisplatin resistance of NSCLC cells by regulating proliferation, apoptosis and autophagy via miR-337-3p/ADAM28 axis. Cancer biomarkers : section A of Disease markers 52 33682697
2008 Polymorphisms in genes involved in neurodevelopment may be associated with altered brain morphology in schizophrenia: preliminary evidence. Psychiatry research 52 19054571
2022 CD20+CD22+ADAM28+ B Cells in Tertiary Lymphoid Structures Promote Immunotherapy Response. Frontiers in immunology 51 35634306
2004 Epigenetic silencing of the adhesion molecule ADAM23 is highly frequent in breast tumors. Oncogene 51 14661055
2009 ADAM23 negatively modulates alpha(v)beta(3) integrin activation during metastasis. Cancer research 47 19549921
2005 Molecular, biochemical, and cellular characterization of epididymal ADAMs, ADAM7 and ADAM28. Biochemical and biophysical research communications 43 15883027
2019 ADAM22 and ADAM23 modulate the targeting of the Kv1 channel-associated protein LGI1 to the axon initial segment. Journal of cell science 37 30598502
2016 MicroRNA-552 enhances metastatic capacity of colorectal cancer cells by targeting a disintegrin and metalloprotease 28. Oncotarget 36 27661126
2007 Binding of ADAM28 to P-selectin glycoprotein ligand-1 enhances P-selectin-mediated leukocyte adhesion to endothelial cells. The Journal of biological chemistry 35 17597069
2004 ADAM23 is a cell-surface glycoprotein expressed by central nervous system neurons. Journal of neuroscience research 34 15505805
2010 Connective tissue growth factor is a substrate of ADAM28. Biochemical and biophysical research communications 32 20971063
2019 Oncogenic ADAM28 induces gemcitabine resistance and predicts a poor prognosis in pancreatic cancer. World journal of gastroenterology 30 31602160
2015 CXCL12 and ADAM23 hypermethylation are associated with advanced breast cancers. Translational research : the journal of laboratory and clinical medicine 30 25620615
2013 Ectodomain shedding of CD200 from the B-CLL cell surface is regulated by ADAM28 expression. Leukemia research 30 23643150
2012 Leucine-rich glioma inactivated 3 regulates adipogenesis through ADAM23. Biochimica et biophysica acta 29 22405860
2012 A synthetic interaction screen identifies factors selectively required for proliferation and TERT transcription in p53-deficient human cancer cells. PLoS genetics 29 23284306
2011 Characterization of ADAM28 as a biomarker of bladder transitional cell carcinomas by urinary proteome analysis. Biochemical and biophysical research communications 28 21782798
2010 ADAM28 is a serological and histochemical marker for non-small-cell lung cancers. International journal of cancer 28 20112342
2003 Integrin alpha4beta1-dependent adhesion to ADAM 28 (MDC-L) requires an extended surface of the disintegrin domain. Biochemistry 28 12667064
2009 Promoter hypermethylation of the ADAM23 gene in colorectal cancer cell lines and cancer tissues. International journal of cancer 27 19089928
2021 Mechanism and Role of the Neuropeptide LGI1 Receptor ADAM23 in Regulating Biomarkers of Ferroptosis and Progression of Esophageal Cancer. Disease markers 25 35003396
2019 MiR-198 affects the proliferation and apoptosis of colorectal cancer through regulation of ADAM28/JAK-STAT signaling pathway. European review for medical and pharmacological sciences 25 30840270
2016 ADAM23 is downregulated in side population and suppresses lung metastasis of lung carcinoma cells. Cancer science 25 26800504
2011 Modulation of integrin α4β1 by ADAM28 promotes lymphocyte adhesion and transendothelial migration. Cell biology international 25 21332445
2022 LncRNA NEAT1 induces autophagy through the miR-128-3p/ADAM28 axis to suppress apoptosis of nonsmall-cell lung cancer. The Kaohsiung journal of medical sciences 24 36054559
2016 Dendritic cell expression of ADAM23 governs T cell proliferation and cytokine production through the α(v)β(3) integrin receptor. Journal of leukocyte biology 24 27317750
2023 Antagonistic roles of canonical and Alternative-RPA in disease-associated tandem CAG repeat instability. Cell 23 37827155
2012 ADAM28 is elevated in humans with the metabolic syndrome and is a novel sheddase of human tumour necrosis factor-α. Immunology and cell biology 23 23010875
2009 ADAM28 as a target for human cancers. Current pharmaceutical design 23 19601836
2018 ADAM23 in Cardiomyocyte Inhibits Cardiac Hypertrophy by Targeting FAK - AKT Signaling. Journal of the American Heart Association 21 30371220
2015 Identification of a common risk haplotype for canine idiopathic epilepsy in the ADAM23 gene. BMC genomics 21 26084559
2023 Sequential genome-wide CRISPR-Cas9 screens identify genes regulating cell-surface expression of tetraspanins. Cell reports 20 36724073
2017 ADAM23 is a common risk gene for canine idiopathic epilepsy. BMC genetics 20 28143391
2016 Secretion-Positive LGI1 Mutations Linked to Lateral Temporal Epilepsy Impair Binding to ADAM22 and ADAM23 Receptors. PLoS genetics 19 27760137
2014 Intratumoral heterogeneity of ADAM23 promotes tumor growth and metastasis through LGI4 and nitric oxide signals. Oncogene 19 24662834
2011 Urinary protein profiling by liquid chromatography/tandem mass spectrometry: ADAM28 is overexpressed in bladder transitional cell carcinoma. Rapid communications in mass spectrometry : RCM 19 21913264
2010 ADAM28: a potential oncogene involved in asbestos-related lung adenocarcinomas. Genes, chromosomes & cancer 19 20544843
2015 ADAM28 overexpression regulated via the PI3K/Akt pathway is associated with relapse in de novo adult B-cell acute lymphoblastic leukemia. Leukemia research 18 26340916
2014 The roles of ADAM33, ADAM28, IL-13 and IL-4 in the development of lung injuries in children with lethal non-pandemic acute infectious pneumonia. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 18 25453333
2018 ADAM28 promotes tumor growth and dissemination of acute myeloid leukemia through IGFBP-3 degradation and IGF-I-induced cell proliferation. Cancer letters 17 30429106
2016 ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death. The FEBS journal 17 26918856
2005 ADAM23 methylation and expression analysis in brain tumors. Neuroscience letters 16 15862898
1999 Identification, sequence analysis and expression of transcripts encoding a putative metalloproteinase, eMDC II, in human and macaque epididymis. Molecular human reproduction 16 10587367
2017 ADAM23 promotes neuronal differentiation of human neural progenitor cells. Cellular & molecular biology letters 15 28828010
2011 ADAM28 manipulates proliferation, differentiation, and apoptosis of human dental pulp stem cells. Journal of endodontics 15 21329817
2023 LGI3/2-ADAM23 interactions cluster Kv1 channels in myelinated axons to regulate refractory period. The Journal of cell biology 14 36828548
2021 ADAM28 from both endothelium and gastric cancer cleaves von Willebrand Factor to eliminate von Willebrand Factor-induced apoptosis of gastric cancer cells. European journal of pharmacology 14 33675784
2020 ADAM28: Another ambivalent protease in cancer. Cancer letters 14 32861707
2018 SUMO-specific protease 2 (SENP2) suppresses keratinocyte migration by targeting NDR1 for de-SUMOylation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 14 29969578
2007 ADAM23 plays multiple roles in neuronal differentiation of P19 embryonal carcinoma cells. Neurochemical research 14 17333391
2019 ADAM23 is a negative regulator of Kv1.1/Kv1.4 potassium currents. Neuroscience letters 13 30965109
2018 Decreased methylation in the SNAI2 and ADAM23 genes associated with de-differentiation and haematogenous dissemination in breast cancers. BMC cancer 13 30189837
2017 Serum levels of ADAM10, ADAM12, ADAM17 AND ADAM28 in colorectal cancer patients. Journal of biological regulators and homeostatic agents 13 29254295
2011 A proteomic approach for identification and localization of the pericellular components of chondrocytes. Histochemistry and cell biology 13 21698479
2006 ADAM28 participates in the regulation of tooth development. Archives of oral biology 13 16836973
2017 CD19 regulates ADAM28-mediated Notch2 cleavage to control the differentiation of marginal zone precursors to MZ B cells. Journal of cellular and molecular medicine 12 28707394
2016 Overexpression and knock-down studies highlight that a disintegrin and metalloproteinase 28 controls proliferation and migration in human prostate cancer. Medicine 12 27749584
2011 The expression of ADAM23 and its correlation with promoter methylation in non-small-cell lung carcinoma. International journal of experimental pathology 12 21429053
2018 Selective Inhibition of ADAM28 Suppresses Lung Carcinoma Cell Growth and Metastasis. Molecular cancer therapeutics 11 30190423
2017 The Metalloproteinase ADAM28 Promotes Metabolic Dysfunction in Mice. International journal of molecular sciences 11 28430139
2009 Characterization of a specific interaction between ADAM23 and cellular prion protein. Neuroscience letters 11 19477226
2009 Overexpression of A disintegrin and metalloproteinase 28 is correlated with high histologic grade in conventional chondrosarcoma. Human pathology 11 19896699
2008 Essential role of ADAM28 in regulating the proliferation and differentiation of human dental papilla mesenchymal cells (hDPMCs). Histochemistry and cell biology 11 18690470
2024 Oligodendrocyte-derived LGI3 and its receptor ADAM23 organize juxtaparanodal Kv1 channel clustering for short-term synaptic plasticity. Cell reports 10 38194969
2018 Microenvironment-derived ADAM28 prevents cancer dissemination. Oncotarget 10 30647853
2013 Expression of ADAM28 and IGFBP-3 genes in patients with colorectal cancer - a preliminary report. International journal of immunopathology and pharmacology 10 23527725
2009 All-trans retinoic acid-induced ADAM28 degrades proteoglycans in human chondrocytes. Biochemical and biophysical research communications 10 19527685
2018 Epstein-Barr Virus Nuclear Antigen 3C Inhibits Expression of COBLL1 and the ADAM28-ADAMDEC1 Locus via Interaction with the Histone Lysine Demethylase KDM2B. Journal of virology 9 30135119
2013 Localization of the gene for hyperostosis cranialis interna to chromosome 8p21 with analysis of three candidate genes. Calcified tissue international 9 23640157
2013 Src plays a key role in ADAM28 expression in v-src-transformed epithelial cells and human carcinoma cells. The American journal of pathology 9 24007880
2023 Identification of ADAM23 as a Potential Signature for Psoriasis Using Integrative Machine-Learning and Experimental Verification. International journal of general medicine 7 38148887
2020 MicroRNA-574-3p inhibits the malignant behavior of liver cancer cells by targeting ADAM28. Oncology letters 7 32782619
2015 Differential Expression of ADAM23, CDKN2A (P16), MMP14 and VIM Associated with Giant Cell Tumor of Bone. Journal of Cancer 7 26078788
2004 Two novel isoforms of Adam23 expressed in the developmental process of mouse and human brains. Gene 7 14697522
2012 ADAM23 knockdown promotes neuronal differentiation of P19 embryonal carcinoma cells by up-regulating P27KIP1 expression. Cell biology international 6 22973984
2010 The regulatory role of a disintegrin and metalloproteinase 28 on the biologic property of human periodontal ligament stem cells. Journal of periodontology 5 20450360
2023 Role for the metalloproteinase ADAM28 in the control of airway inflammation, remodelling and responsiveness in asthma. Frontiers in immunology 4 36685493
2017 ADAM28 localizes to HLA-G+ trophoblasts and promotes column cell outgrowth. Placenta 4 28623976
2010 SP1 acts as a key factor, contributes to upregulation of ADAM23 expression under serum deprivation. Biochemical and biophysical research communications 4 20851106
2009 Influence of ADAM28 on biological characteristics of human dental follicle cells. Archives of oral biology 4 19580958
2020 Endocytosis of the non-catalytic ADAM23: Recycling and long half-life properties. Experimental cell research 3 33296662
2010 ADAM23, a Gene Related to LGI1, Is Not Linked to Autosomal Dominant Lateral Temporal Epilepsy. Epilepsy research and treatment 3 22937229
2018 Monoclonal Antibody DL11C8 Identifies ADAM23 as a Component of Lipid Raft Microdomains. Neuroscience 2 29792904
2010 [ADAM28: involvement in cancer cell proliferation, invasion and metastasis]. Seikagaku. The Journal of Japanese Biochemical Society 2 21077327
2025 Research progress on ADAM28 in malignant tumors. Discover oncology 1 40252142
2025 Biallelic LGI1 and ADAM23 variants cause hippocampal epileptic encephalopathy via the LGI1-ADAM22/23 pathway. Brain : a journal of neurology 1 40455867
2023 A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating γ-secretase complex. Neuro-oncology advances 1 38024245
2018 ADAM28 dramatically regulates the biological features of human gingival fibroblasts. Odontology 1 30552542
2014 [Research advances on ADAM28 expression and ADAM28-mediated tumor metastasis]. Zhongguo shi yan xue ye xue za zhi 1 25130845
2009 [Effects of ADAM28 AS-ODN on proliferation, differentiation and apoptosis of HPDLSC]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 1 19907862
2007 Genomic organization of the region spanning D14Mit262 and D14Mit86 on mouse chromosome 14 and exclusion of Adam28 and Adamdec1 as the cataract-causing gene, lr2. Cytogenetic and genome research 1 17268172
2026 Species-Specific Parent-Of-Origin Expression of Adam23 in the Mammalian Brain. Genes to cells : devoted to molecular & cellular mechanisms 0 41568889
2026 Epitranscriptomic Regulation of Platinum Resistance via the METTL3-ADAM23 Axis in Ovarian Cancer. Cells 0 41677656
2025 ADAM28 promotes epithelial mesenchymal transition and impairs tight junctions in non-eosinophilic chronic rhinosinusitis with nasal polyps by inducing M1 polarization of macrophages. International immunopharmacology 0 39954661
2025 Case Report: Anti-ADAM23 antibody: an overlooked autoantibody against VGKC-complex in autoimmune encephalitis. Frontiers in immunology 0 40519920
2025 ADAM23 haploinsufficiency as a putative oligogenic contributor in an individual with focal epilepsy. Seizure 0 40865352
2025 Histone-, Receptor-, and Integrin-Related Gene Products and ADAM28 as Relevant to B-Cell Acute Lymphoblastic Leukemia (B-ALL). Current issues in molecular biology 0 41020821
2023 Differential Expressions of ADAM28 and ADAMTSL3 in Gingival Tissue of Patients with Periodontitis. The Tohoku journal of experimental medicine 0 36927684
2020 [Construction of ADAM28 shRNA interference vector and its inhibitory effect on human periodontal ligament stem cells]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 0 33543212
2014 [The effects of ADAM28 AS-ODN on biological function of human gingival fibroblasts]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 0 25543593
2010 [Effects of ADAM28 on biological functions of human dental pulp stem cells]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 0 20635038
2008 [The effects of ADAM28 on HDPC biological characteristics]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 0 18661070
2007 [The construction of ADAM28 eukaryotic expression plasmid and expression after transfected into HDFC]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 0 17924028
2006 [Effects of ADAM28 AS-ODN on proliferation and AKPase of HDFCs]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 0 16685358