Affinage

DSG2

Desmoglein-2 · UniProt Q14126

Length
1118 aa
Mass
122.3 kDa
Annotated
2026-04-28
77 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DSG2 is a ubiquitously expressed desmosomal cadherin that mediates Ca²⁺-dependent cell-cell adhesion through homophilic and heterophilic strand-swap dimerization and couples intercellular junctions to intracellular signaling networks controlling proliferation, survival, and tissue integrity. Its extracellular domain engages in homophilic binding with high activation-barrier kinetics consistent with strand-swapping, forms heterophilic dimers with DSG3 and P-cadherin, and carries sialylated N-glycans that engage macrophage Siglec-9 to suppress phagocytosis (PMID:29062102, PMID:33193387, PMID:39813162). Intracellularly, DSG2 binds plakoglobin (via armadillo repeat 4), organizes lipid raft signaling platforms to activate EGFR through c-Src/Caveolin-1-dependent transactivation driving PI3K/AKT, MEK-MAPK, STAT3, and NF-κB cascades, and is phosphorylated by PRKD2 at T730 to potentiate EGFR/Src/AKT/ERK signaling (PMID:8749329, PMID:26918609, PMID:38411280). Loss-of-function and dominant-negative DSG2 mutations cause arrhythmogenic cardiomyopathy through myocyte necrosis, ER stress–PERK–ATF4–TGF-β1-driven fibrosis, and impaired mTOR–PPARα-dependent fatty acid oxidation, establishing DSG2 as a causal gene for this disease (PMID:19635863, PMID:39227800, PMID:36815030).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 High

    Establishing DSG2 as the ubiquitous desmosomal cadherin resolved the question of which desmoglein isoform is present across all desmosome-bearing tissues, providing the foundation for all subsequent functional studies.

    Evidence cDNA cloning, sequence analysis, and Northern blot across multiple tissues

    PMID:8143788

    Open questions at the time
    • No functional assay of adhesion performed
    • Protein-level expression not quantified across tissues
  2. 1996 High

    Demonstration that DSG2 localizes to desmosomes and half-desmosomes on uncoupled cell surfaces established its direct participation in cell-cell coupling rather than merely being a desmosome-associated protein.

    Evidence Immunocytochemistry with multiple antibodies in stratified/simple epithelia and myocardium

    PMID:8641550

    Open questions at the time
    • No dynamic assembly or turnover measurement
    • Localization in non-epithelial cell types incompletely mapped
  3. 1995 High

    Identification of the plakoglobin–DSG2 interaction via armadillo repeat 4 defined the first direct cytoplasmic binding partner, explaining how DSG2 couples to the desmosomal plaque.

    Evidence In vitro binding assay with bacterially expressed deletion mutants of plakoglobin

    PMID:8749329

    Open questions at the time
    • No in vivo validation of armadillo repeat 4 requirement
    • Other cytoplasmic partners not addressed
  4. 2007 High

    Transgenic DSG2 overexpression in mouse epidermis revealed that DSG2 is not merely a structural adhesion molecule but an activator of PI3K/AKT, MEK-MAPK, STAT3, and NF-κB signaling via EGFR, explaining how desmosomal cadherins influence proliferation and tumor susceptibility.

    Evidence Involucrin-Dsg2 transgenic mice with pathway inhibitor studies and chemical carcinogenesis

    PMID:17284515

    Open questions at the time
    • Direct DSG2–EGFR interaction mechanism not resolved
    • Signaling model based on overexpression, not endogenous levels
  5. 2009 High

    The Dsg2-N266S transgenic mouse demonstrated that ARVC-associated DSG2 mutations act in a dominant-negative manner, with myocyte necrosis as the initiating event preceding fibrofatty replacement — establishing the disease mechanism in vivo.

    Evidence Cardiac-specific transgenic mouse with graded expression levels, histopathology, electrophysiology

    PMID:19635863

    Open questions at the time
    • Whether necrosis versus apoptosis predominates remained debated
    • Downstream molecular pathways from DSG2 loss to necrosis not defined
  6. 2016 High

    Mechanistic dissection of DSG2-EGFR crosstalk showed that DSG2 organizes lipid raft platforms and displaces Caveolin-1, enabling c-Src-dependent EGFR transactivation — explaining the signaling effects observed in transgenic mice.

    Evidence Sucrose density fractionation, STED imaging, siRNA knockdown, MβCD perturbation in SCC cells

    PMID:26918609

    Open questions at the time
    • Direct physical DSG2–EGFR binding not demonstrated at this stage
    • Mechanism of Cav1 displacement unclear
  7. 2017 High

    Single-molecule force spectroscopy revealed that DSG2 homophilic dimerization follows strand-swap mechanics with a high activation barrier, and that ARVC mutations alter binding kinetics without disrupting the binding motif — providing a biophysical explanation for how mutations weaken adhesion.

    Evidence Single-molecule AFM force spectroscopy with Jarzynski analysis plus dispase assay in HT1080 cells

    PMID:29062102

    Open questions at the time
    • Structural basis of kinetic changes not resolved at atomic level
    • In vivo relevance of altered kinetics not tested
  8. 2018 High

    Direct DSG2–EGFR interaction on living enterocyte surfaces was confirmed by AFM, and DSG2 was shown to be required for EGFR junctional localization via Src, closing the gap between lipid raft models and direct receptor engagement.

    Evidence AFM on living cells, Co-IP, siRNA knockdown in enterocytes with barrier function readout

    PMID:29980799

    Open questions at the time
    • Binding interface between DSG2 and EGFR ectodomains not mapped
    • Whether interaction is direct or adaptor-mediated at atomic resolution unknown
  9. 2020 High

    Discovery of heterophilic DSG2–DSG3 binding with catch-bond behavior and longer lifetime than homophilic interactions expanded the adhesion model beyond homodimerization and explained partial resistance to pemphigus autoantibodies.

    Evidence Cell-free AFM and Co-IP with Dsg3-deficient keratinocytes and pemphigus skin ex vivo model

    PMID:33193387

    Open questions at the time
    • Structural basis of heterophilic versus homophilic preference not determined
    • In vivo significance of heterophilic binding in intact desmosomes not tested
  10. 2022 High

    Cardiac-specific Dsg2 knockout revealed that DSG2 loss causes lipid accumulation and cardiac dysfunction through impaired mTOR–4EBP1–PPARα signaling and parallel STAT3/SMAD3-driven fibrosis, providing the first metabolic explanation for arrhythmogenic cardiomyopathy pathogenesis downstream of desmosome disruption.

    Evidence Cardiac-specific Dsg2 KO mice with rapamycin worsening, AAV-PPARα rescue, fenofibrate treatment, siRNA epistasis in HL-1 cells

    PMID:36291052 PMID:36815030

    Open questions at the time
    • How DSG2 loss signals to mTOR not defined
    • Whether metabolic dysfunction is primary or secondary to structural defects unclear
  11. 2024 High

    Identification of PRKD2 as the kinase phosphorylating DSG2 at T730 established the first site-specific post-translational modification that potentiates DSG2-EGFR/Src/AKT/ERK signaling, linking kinase signaling directly to desmosomal cadherin function in cancer cell migration.

    Evidence Interactome analysis, phosphorylation assay, T730A mutagenesis, migration/invasion assays in ESCC cells

    PMID:38411280

    Open questions at the time
    • Whether T730 phosphorylation occurs in normal tissues unknown
    • Phosphatase responsible for dephosphorylation not identified
  12. 2024 High

    The Dsg2-F531C knock-in mouse showed that ARVC mutations can trigger ER stress through BiP recognition of misfolded DSG2, activating PERK–ATF4–TGF-β1 paracrine signaling from cardiomyocytes to fibroblasts — providing a proteostasis-based fibrosis mechanism distinct from the mTOR/PPARα axis.

    Evidence CRISPR knock-in mice, Co-IP with BiP, transcriptomics, MS, PERK inhibitor rescue

    PMID:39227800

    Open questions at the time
    • Whether ER stress pathway is universal across all ARVC-associated DSG2 mutations not tested
    • Relative contribution of ER stress versus metabolic pathways to disease unclear
  13. 2025 High

    Identification of DSG2 as the dominant Siglec-9 counter-receptor on melanoma cells, dependent on sialylated N-glycans, revealed a glyco-immune checkpoint function for DSG2 as a 'don't eat me' signal — expanding its role beyond adhesion into immune evasion.

    Evidence Proximity labeling, CRISPR KO screening, glycan dependency analysis, macrophage phagocytosis assay

    PMID:39813162

    Open questions at the time
    • Whether DSG2–Siglec-9 interaction occurs in non-melanoma contexts unknown
    • In vivo therapeutic significance of blocking this axis not yet established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structure of DSG2 in complex with EGFR and Siglec-9, the mechanism by which DSG2 loss activates mTOR suppression in cardiomyocytes, and whether the ER stress and metabolic pathways represent parallel or convergent disease mechanisms in arrhythmogenic cardiomyopathy.
  • No crystal/cryo-EM structure of DSG2 ectodomain complexes with non-cadherin partners
  • Mechanism linking DSG2 loss to mTOR inactivation undefined
  • Relative contributions of ER stress versus metabolic versus mechanical defects to ARVC progression unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 5 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 1
Pathway
R-HSA-1500931 Cell-Cell communication 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1430728 Metabolism 1 R-HSA-168256 Immune System 1
Partners
DSG3EGFRGJA1JUPPKP2PRKD2SIGLEC9TROP2
Complex memberships
desmosomeintercalated disc

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 DSG2 was identified as the ubiquitous desmoglein isoform present in all desmosome-containing tissues (epithelia, myocardium, lymph node follicles), encoding a 1069 amino acid transmembrane glycoprotein that functions as a Ca2+-dependent cell adhesion molecule and component of the desmosomal cadherin complex. cDNA cloning, amino acid sequence analysis, Northern blot, tissue expression profiling Experimental cell research High 8143788
1996 DSG2 protein localizes to desmosomes in all desmosome-containing tissues including stratified and simple epithelia, myocardium, and lymph node follicles; in stratified squamous epithelia, DSG2 is restricted to the basal cell layer. Antibodies to extracellular domains react with half-desmosomes on surfaces of uncoupled epithelial cells, demonstrating its role in cell-cell coupling. Immunocytochemistry with monoclonal and polyclonal antibodies targeting extracellular and cytoplasmic domains Differentiation; research in biological diversity High 8641550
1995 The fourth armadillo repeat of plakoglobin is required for its high-affinity binding to the cytoplasmic domain of DSG2; bacterially expressed 12-repeat plakoglobin (lacking the fourth repeat) binds DSG2 with lower affinity than the 13-repeat form, establishing DSG2 as a direct binding partner of plakoglobin at desmosomes. In vitro binding assay with bacterially expressed proteins, deletion mutant analysis Journal of biochemistry High 8749329
2007 Suprabasal overexpression of DSG2 in transgenic mouse epidermis causes keratinocyte hyperproliferation, apoptosis resistance, and skin tumor susceptibility through activation of multiple signaling pathways including PI3K/AKT, MEK-MAPK, STAT3, and NF-κB, with enhanced EGF receptor activation required for anchorage-independent survival. Transgenic mouse model (involucrin-promoter Dsg2), ex vivo keratinocyte culture, pathway inhibitor studies, chemical carcinogenesis assay Journal of cell science High 17284515
2009 The DSG2-N266S mutation acts in a dominant-negative, dose-dependent manner to cause arrhythmogenic right ventricular cardiomyopathy (ARVC) in transgenic mice; myocyte necrosis is the key initiating event, triggering inflammatory response, calcification, fibrous tissue replacement, and myocardial atrophy. Cardiac-specific transgenic mouse overexpressing mutant dsg2 (N271S), multiple transgene expression levels, histopathology, electrophysiology The Journal of experimental medicine High 19635863
2016 DSG2 activates EGFR signaling through a c-Src and Caveolin-1 (Cav1)-dependent mechanism via lipid rafts: DSG2 overexpression recruits to and displaces Cav1, EGFR, and c-Src from light-density lipid raft fractions, leading to c-Src and EGFR activation, increased cell proliferation and migration. DSG2 knockdown abrogates EGFR, c-Src, and STAT3 activation in response to EGF. Sucrose density fractionation, STED imaging, siRNA knockdown, overexpression in SCC cells, proliferation and migration assays, lipid raft perturbation (MβCD) Oncotarget High 26918609
2017 ARVC-associated DSG2 mutations (studied by single-molecule force spectroscopy) significantly alter the kinetics and thermodynamics of homophilic DSG2 dimerization without directly affecting the binding motif; the free energy landscape of DSG2 dimerization reveals a high activation barrier consistent with a strand-swapping binding motif, and mutations reduce cell-cell adhesion in a dispase-based assay. Single-molecule force spectroscopy, Jarzynski's equality for thermodynamic analysis, dispase-based cell dissociation assay with HT1080 cells overexpressing WT and mutant Dsg2 Scientific reports High 29062102
2018 DSG2 directly interacts with EGFR and undergoes heterotypic binding events on the surface of living enterocytes via its extracellular domain; DSG2 is required for EGFR localization at intercellular junctions and for Src-mediated EGFR activation; Src binds EGFR and is required for co-localization of EGFR and DSG2 at cell-cell contacts. DSG2-deficient enterocytes show impaired barrier properties and increased proliferation. Atomic force microscopy on living cells, Co-IP, siRNA knockdown, EGFR localization imaging, barrier function assays Cellular and molecular life sciences High 29980799
2018 DSG2 regulates self-renewal and pluripotency of human pluripotent stem cells predominantly through β-catenin/Slug-mediated epithelial-to-mesenchymal transition (EMT); DSG2 depletion markedly decreased hPSC proliferation, pluripotency marker expression, and embryonic body and teratoma formation. Monoclonal antibody-based identification, siRNA knockdown, flow cytometry, embryoid body and teratoma assays, Western blot for β-catenin/Slug pathway Stem cell reports Medium 29910125
2019 ARVC-associated DSG2 mutations alter the N-glycosylation pattern of desmoglein-2; wildtype and mutant DSG2 display different glycosylation patterns despite mutations not directly affecting N-glycosylation consensus sequences, indicating complex molecular interactions between DSG2 mutations and N-glycosylations. De-glycosylation assays, lectin blot analysis, genetic inhibition of glycosylation Journal of molecular and cellular cardiology Medium 30885746
2020 DSG2 undergoes heterophilic interactions with DSG3; immunoprecipitation and cell-free atomic force microscopy demonstrated Dsg2-Dsg3 heterophilic binding with comparable frequency, strength, Ca2+-dependency, and catch-bond behavior to homophilic interactions, but with longer lifetime. Heterophilic Dsg2-Dsg3 interactions are significantly less inhibited by pemphigus vulgaris autoantibodies compared to homophilic Dsg3 interactions. Co-immunoprecipitation, cell-free atomic force microscopy, Dsg3-deficient keratinocyte model, pemphigus skin ex vivo model Frontiers in immunology High 33193387
2020 DSG2 knockdown in anaplastic thyroid cancer cells increased cell migration and invasion through the c-Met/Src/Rac1 signaling axis without altering EMT markers; specific c-Met inhibition blocked motility of shDsg2-depleted cells, and decreased membrane DSG2 increased metastatic potential in vivo. shRNA knockdown, migration/invasion assays, in vivo metastasis model, pharmacological c-Met inhibition, Western blot for signaling intermediates Endocrine-related cancer Medium 33022637
2021 A DSG2 truncation mutation (p.S363X) localized in the extracellular domain results in absence of the truncated protein at the plasma membrane, as shown by in vitro transfection experiments, supporting loss-of-function through failure of membrane trafficking. In vitro cell transfection, immunofluorescence localization of truncated vs. wildtype DSG2 International journal of molecular sciences Medium 34202524
2022 Cardiac-specific knockout of Dsg2 causes myocardial lipid accumulation and cardiac dysfunction through impaired fatty acid β-oxidation resulting from declined mTOR-4EBP1-PPARα signaling; rapamycin worsened while mTOR/4EBP1 overexpression or PPARα reactivation (fenofibrate/AAV9-Pparα) rescued the phenotype. Cardiac-specific Dsg2 knockout mouse, echocardiography, lipid staining, Western blot, AAV-mediated gene delivery, rapamycin treatment, pharmacological PPARα activation Acta pharmaceutica Sinica. B High 36815030
2022 Dsg2 deficiency causes cardiac fibrosis via PPARα deficiency and hyperactivation of STAT3 and SMAD3; Dsg2 gene silencing in HL-1 cells upregulates fibrotic markers (α-SMA, Collagen I); STAT3 siRNA inhibits fibrotic marker expression; PPARα activation by fenofibrate or AAV9-Pparα reduces fibrosis and decreases phosphorylation of STAT3, SMAD3, and AKT. CS-Dsg2-/- mouse, Masson staining, Western blot, qPCR, siRNA knockdown in HL-1 cells, AAV gene delivery Cells High 36291052
2022 TROP2 interacts with DSG2 in gastric cancer cells (identified by co-immunoprecipitation and mass spectrometry); TROP2 overexpression reduces DSG2 levels and desmosome adhesion, promoting cell invasion and migration through EGFR/AKT and DSG2/plakoglobin/β-catenin pathways. Co-immunoprecipitation, mass spectrometry, TROP2 overexpression/knockdown, electron microscopy of desmosome assembly, Western blot for pathway analysis Current cancer drug targets Medium 35392784
2024 PRKD2 (serine/threonine-protein kinase D2) phosphorylates DSG2 at threonine 730 (T730); this phosphorylation promotes esophageal squamous cell carcinoma cell migration and invasion by activating EGFR, Src, AKT, and ERK signaling pathways; DSG2-T730 phosphorylation-deficient mutants abolish the pro-migratory effect. Interactome analysis, phosphorylation assay, site-directed mutagenesis (T730), migration/invasion assays, Western blot for signaling pathways The Journal of pathology High 38411280
2024 DSG2 F531C mutation causes protein misfolding recognized by BiP within the endoplasmic reticulum, triggering ER stress and activating PERK-ATF4 signaling; elevated ATF4 increases TGF-β1 expression in cardiomyocytes, which activates cardiac fibroblasts via paracrine signaling to promote cardiac fibrosis; PERK-ATF4 inhibition attenuated fibrosis in knock-in mice. Dsg2 F536C knock-in mice (CRISPR/Cas9), transcriptomic analysis, mass spectrometry, Co-IP with BiP, neonatal/adult cardiomyocytes isolation, PERK inhibitor treatment, histopathology BMC medicine High 39227800
2024 DSG2 ectodomain organization (measured by fluorescence polarization) gradually increases over 8 hours during desmosome assembly and correlates with increasing adhesive strength; in wound healing, ectodomain order increases in assembling desmosomes at the leading edge of migratory cells. Fluorescence polarization microscopy, scratch wound assay, time-lapse imaging Cell adhesion & migration Medium 38566311
2025 DSG2 is identified as a dominant counter receptor of Siglec-9 in melanoma cells via proximity labeling and CRISPR knockout screening; the DSG2-Siglec-9 interaction is mainly dependent on sialic acid-bearing N-glycans on DSG2; blocking this interaction significantly enhances macrophage phagocytosis of melanoma cells. Proximity labeling, CRISPR knockout screening, binding assays, macrophage phagocytosis assay, glycan dependency analysis Advanced science High 39813162
2024 DSG2 interacts with c-MYC (by co-immunoprecipitation) in cervical cancer cells; DSG2 overexpression combined with c-MYC inhibition significantly decreases cell proliferation, migration, and ADAM17 expression compared to DSG2 overexpression alone, placing DSG2 upstream of c-MYC/ADAM17 in a proliferation/migration pathway. Co-immunoprecipitation, c-MYC inhibitor treatment, qPCR, Western blot, CCK-8 and Transwell assays Cancer management and research Medium 38948682
2025 DSG2 deficiency in cardiomyocytes results in Z-disc structural defects and increased myosin detachment rate; Ca2+-activated force is markedly reduced in DSG2-mutant permeabilized left ventricular cardiac muscle bundles but preserved in isolated permeabilized cardiomyocytes, revealing that DSG2 is required for force transmission between sarcomeres (tissue-level mechanotransduction) in addition to cell-cell mechanical coupling. Homozygous Dsg2 knock-in mice (adolescent and adult), permeabilized cardiac muscle bundles vs. isolated cardiomyocyte force measurements, X-ray diffraction, echocardiography bioRxivpreprint Medium bio_10.1101_2025.10.03.680335
2025 Proximity labeling and quantitative mass spectrometry identified over 300 proteins in the DSG2 interactome in neonatal cardiomyocytes; unique DSG2-associated proteins include connexin 43 (gap junction protein) and plakin family cytolinker proteins; plakoglobin (JUP) and plakophilin 2 (PKP2) are the most abundant proteins shared between DSG2 and N-cadherin interactomes. Proximity labeling (BioID), quantitative mass spectrometry, comparison with N-cadherin interactome bioRxivpreprint Medium bio_10.1101_2025.06.09.658637
2025 P-cadherin (Pcad) facilitates desmosome assembly by directly interacting with DSG2 on opposing cells via heterophilic strand-swap dimerization involving conserved tryptophan residues; stiffening the hinge on the swapped β-strands reduces heterophilic dimer formation; introduction of strand-swap competent Pcad into cells lacking classical cadherins rescues desmosome assembly. Single-molecule atomic force microscopy, super-resolution and confocal imaging, site-directed mutagenesis of strand-swap residues, atomistic simulations, cell-based desmosome assembly assay bioRxivpreprint Medium bio_10.1101_2025.09.15.676363
2025 Pathogenic autoantibodies from ACM patients bind DSG2 in hiPSC-CMs, cleave DSG2, and reduce DSG2 interaction at the molecular level; these autoantibodies impair cardiomyocyte cohesion by activating GSK-3β upstream of p38MAPK, leading to phosphorylation and junctional loss of β-catenin; GSK-3β inhibition rescues the loss of cell cohesion induced by ACM autoantibodies. hiPSC-cardiomyocytes from ACM patients, IgG fractionation, dispase dissociation assay, GSK-3β inhibition, Western blot for p38MAPK/β-catenin phosphorylation bioRxivpreprint Medium bio_10.1101_2025.06.25.661311
2025 Oxymatrine (OMT) directly binds DSG2 (confirmed by CETSA, DARTS, and microscale thermophoresis) and stabilizes it; OMT and its metabolite matrine reduce DSG2 cleavage by inhibiting caspase-8 activity, thereby enhancing intestinal epithelial barrier function; knockdown of DSG2 abolishes the protective effects of OMT. CETSA, DARTS, microscale thermophoresis, caspase-8 activity assay, lentiviral DSG2 knockdown, Caco-2 and FD duodenal spheroid models Phytomedicine High 41076918
2025 DSG2 mediates conversion between desmosome and adherens junctions in circulating tumor cell (CTC) clusters; high DSG2 expression maintains desmosome-dominant intercellular junctions in CTC clusters; HIF-1α positively controls DSG2-mediated desmosome junctions; inhibiting HIF-1α promotes conversion from desmosome to adherens junctions, destabilizing CTC clusters. CTC cluster analysis, junction protein characterization by IF, HIF-1α inhibition, in vivo metastasis models Experimental & molecular medicine Medium 41381723
2010 Ectopic suprabasal expression of DSG2 in transgenic mice reduces epidermal blister formation in response to pemphigus foliaceus antibodies and exfoliative toxins (ETA); DSG2 overexpression enhances retention of DSG1 at cell-cell borders, demonstrating DSG2's direct role in cell adhesion and protection of desmosomal components. Transgenic mouse model (involucrin-Dsg2), injection of ETA and PF IgG, immunofluorescence for Dsg1 localization Dermatology research and practice Medium 20631906
2006 UV radiation induces DSG2 downregulation in human lens epithelial cells via EGFR activation, Rac2 translocation, and NADPH oxidase-mediated generation of reactive oxygen species (ROS); this pathway is analogous to that activated by H2O2 treatment. Cell culture, UV irradiation, ROS measurement, EGFR activation assay, Rac2/NADPH oxidase activity, Western blot for DSG2 International journal of molecular medicine Medium 16820949
2015 DSG2 regulates cystatin A (CSTA) expression in keratinocytes; knockdown of DSG2 reduces CSTA expression; conversely, CSTA knockdown causes cytoplasmic mislocalization of DSG2, perturbs cytokeratin 14, reduces desmoplakin levels, and induces loss of cell adhesion. Combined knockdown of DSG2 and CSTA has a synergistic effect on loss of adhesion, demonstrating crosstalk between DSG2 and CSTA in regulating cell-cell adhesion. siRNA/shRNA knockdown, microarray, qPCR, immunoblotting, immunohistochemistry, dispase-based adhesion assay, mechanical stretching PloS one Medium 25785582
2018 DSG2 overexpression in basal keratinocytes accelerates full-thickness wound closure and increases wound-adjacent keratinocyte proliferation; DSG2 induces increased release and proteolytic processing of urokinase-type plasminogen activator receptor (uPAR), and wounding further enhances uPAR and laminin-332 in transgenic epidermis. Transgenic mice (keratin14-Dsg2), wound healing assay, antibody profiler secretome array, immunohistochemistry The Journal of investigative dermatology Medium 29753032

Source papers

Stage 0 corpus · 77 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Identification of the ubiquitous human desmoglein, Dsg2, and the expression catalogue of the desmoglein subfamily of desmosomal cadherins. Experimental cell research 216 8143788
2006 DSG2 mutations contribute to arrhythmogenic right ventricular dysplasia/cardiomyopathy. American journal of human genetics 188 16773573
2009 Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy. The Journal of experimental medicine 167 19635863
2007 Suprabasal Dsg2 expression in transgenic mouse skin confers a hyperproliferative and apoptosis-resistant phenotype to keratinocytes. Journal of cell science 102 17284515
2009 Increased expression of Dsg2 in malignant skin carcinomas: A tissue-microarray based study. Cell adhesion & migration 89 19458482
1996 Immunological identification and characterization of the desmosomal cadherin Dsg2 in coupled and uncoupled epithelial cells and in human tissues. Differentiation; research in biological diversity 85 8641550
2016 c-Src/Cav1-dependent activation of the EGFR by Dsg2. Oncotarget 53 26918609
2012 A new human DSG2-transgenic mouse model for studying the tropism and pathology of human adenoviruses. Journal of virology 52 22457526
1995 The fourth armadillo repeat of plakoglobin (gamma-catenin) is required for its high affinity binding to the cytoplasmic domains of E-cadherin and desmosomal cadherin Dsg2, and the tumor suppressor APC protein. Journal of biochemistry 49 8749329
2018 A founder homozygous DSG2 variant in East Asia results in ARVC with full penetrance and heart failure phenotype. International journal of cardiology 45 30454721
1992 The human gene (DSG2) coding for HDGC, a second member of the desmoglein subfamily of the desmosomal cadherins, is, like DSG1 coding for desmoglein DGI, assigned to chromosome 18. Genomics 40 1612610
2006 UV radiation down-regulates Dsg-2 via Rac/NADPH oxidase-mediated generation of ROS in human lens epithelial cells. International journal of molecular medicine 33 16820949
2015 Cell cycle- and cancer-associated gene networks activated by Dsg2: evidence of cystatin A deregulation and a potential role in cell-cell adhesion. PloS one 29 25785582
2018 Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion. Cellular and molecular life sciences : CMLS 28 29980799
2017 Whole Genome Sequence Identified a Rare Homozygous Pathogenic Mutation of the DSG2 Gene in a Familial Arrhythmogenic Cardiomyopathy Involving Both Ventricles. Cardiology 25 28578331
2018 DSG2 Is a Functional Cell Surface Marker for Identification and Isolation of Human Pluripotent Stem Cells. Stem cell reports 24 29910125
2017 Arrhythmogenic cardiomyopathy related DSG2 mutations affect desmosomal cadherin binding kinetics. Scientific reports 24 29062102
2021 Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset. International journal of molecular sciences 23 33917638
2019 In vitro analysis of arrhythmogenic cardiomyopathy associated desmoglein-2 (DSG2) mutations reveals diverse glycosylation patterns. Journal of molecular and cellular cardiology 19 30885746
2017 Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2. BMC medical genetics 19 28818065
2022 Reactivation of PPARα alleviates myocardial lipid accumulation and cardiac dysfunction by improving fatty acid β-oxidation in Dsg2-deficient arrhythmogenic cardiomyopathy. Acta pharmaceutica Sinica. B 18 36815030
2019 A common indel polymorphism of the Desmoglein-2 (DSG2) is associated with sudden cardiac death in Chinese populations. Forensic science international 17 31220685
2020 Dsg2 Upregulation as a Rescue Mechanism in Pemphigus. Frontiers in immunology 16 33193387
2022 TROP2 Down-regulated DSG2 to Promote Gastric Cancer Cell Invasion and Migration by EGFR/AKT and DSG2/PG/β-Catenin Pathways. Current cancer drug targets 15 35392784
2022 Activation of PPARα Ameliorates Cardiac Fibrosis in Dsg2-Deficient Arrhythmogenic Cardiomyopathy. Cells 15 36291052
2010 Superficial dsg2 expression limits epidermal blister formation mediated by pemphigus foliaceus antibodies and exfoliative toxins. Dermatology research and practice 15 20631906
2021 Desmoglein 2 (DSG2) Is A Receptor of Human Adenovirus Type 55 Causing Adult Severe Community-Acquired Pneumonia. Virologica Sinica 14 34224109
2025 Natural History and Clinical Outcomes of Patients With DSG2/DSC2 Variant-Related Arrhythmogenic Right Ventricular Cardiomyopathy. Circulation 13 40123482
2020 Dsg2-mediated c-Met activation in anaplastic thyroid cancer motility and invasion. Endocrine-related cancer 13 33022637
2021 The Double Mutation DSG2-p.S363X and TBX20-p.D278X Is Associated with Left Ventricular Non-Compaction Cardiomyopathy: Case Report. International journal of molecular sciences 12 34202524
2019 Sudden death in mild hypertrophic cardiomyopathy with compound DSG2/DSC2/MYH6 mutations: Revisiting phenotype after genetic assessment in a master runner athlete. Journal of electrocardiology 12 30716529
2018 Enhancement of Cutaneous Wound Healing by Dsg2 Augmentation of uPAR Secretion. The Journal of investigative dermatology 12 29753032
2024 Hyperactivation of ATF4/TGF-β1 signaling contributes to the progressive cardiac fibrosis in Arrhythmogenic cardiomyopathy caused by DSG2 Variant. BMC medicine 11 39227800
2023 Molecular insight into arrhythmogenic cardiomyopathy caused by DSG2 mutations. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 11 37696084
2022 Up-regulation of Dsg2 confered stem cells with malignancy through wnt/β-catenin signaling pathway. Experimental cell research 11 36375513
2020 Selective elimination of human pluripotent stem cells by Anti-Dsg2 antibody-doxorubicin conjugates. Biomaterials 10 32827795
2018 Compound and heterozygous mutations of DSG2 identified by Whole Exome Sequencing in arrhythmogenic right ventricular cardiomyopathy/dysplasia with ventricular tachycardia. Journal of electrocardiology 9 30177324
2022 Properties of Adenovirus Vectors with Increased Affinity to DSG2 and the Potential Benefits of Oncolytic Approaches and Gene Therapy. Viruses 8 36016457
2018 Case report of familial sudden cardiac death caused by a DSG2 p.F531C mutation as genetic background when carrying with heterozygous KCNE5 p.D92E/E93X mutation. BMC medical genetics 8 30129429
2015 Arrhythmogenic right ventricular cardiomyopathy with left ventricular involvement: a novel splice site mutation in the DSG2 gene. Cardiology 8 25660657
2024 Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression. The Journal of pathology 7 38411280
2019 Distal myopathy induced arrhythmogenic right ventricular cardiomyopathy in a pedigree carrying novel DSG2 null variant. International journal of cardiology 7 31653443
2024 Dsg2 ectodomain organization increases throughout desmosome assembly. Cell adhesion & migration 6 38566311
2022 Serum DSG2 as a potential biomarker for diagnosis of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma. Bioscience reports 6 35521959
2019 Two pedigrees with arrhythmogenic right ventricular cardiomyopathy linked with R49H and F531C mutation in DSG2. Human genome variation 6 31645976
2025 Proximity Labeling and Genetic Screening Reveal that DSG2 is a Counter Receptor of Siglec-9 and Suppresses Macrophage Phagocytosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 39813162
2023 Misdiagnosed myocarditis in arrhythmogenic cardiomyopathy induced by a homozygous variant of DSG2: a case report. Frontiers in cardiovascular medicine 5 37288269
2024 Prevalence and Correlates of Anti-DSG2 Antibodies in Arrhythmogenic Right Ventricular Cardiomyopathy and Myocarditis: Immunological Insights from a Multicenter Study. Journal of clinical medicine 4 39597880
2024 DSG2 and c-MYC Interact to Regulate the Expression of ADAM17 and Promote the Development of Cervical Cancer. Cancer management and research 3 38948682
2018 PKP2 and DSG2 genetic variations in Latvian arrhythmogenic right ventricular dysplasia/cardiomyopathy registry patients. Anatolian journal of cardiology 3 30391969
2025 DSG2 attenuates gemcitabine efficacy through PTX3 in lung adenocarcinoma. Biochimica et biophysica acta. Molecular basis of disease 2 40316058
2025 DSG2 promotes pancreatic cancer stem cell maintenance via support of tumour and macrophage cellular cross-talk. Cell death & disease 2 40615400
2021 CRISPR/Cas9-edited PKP2 knock-out (JMUi001-A-2) and DSG2 knock-out (JMUi001-A-3) iPSC lines as an isogenic human model system for arrhythmogenic cardiomyopathy (ACM). Stem cell research 2 33640690
2021 Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Probably Caused by DSG2 p.Val149Ile Mutation as Genetic Background When Carrying with Heterozygous PRRT2 p.Arg217ProfsTer8 Mutation: A Case Report. International medical case reports journal 2 34012299
2021 Molecular autopsy and subsequent functional analysis reveal de novo DSG2 mutation as cause of sudden death. European journal of medical genetics 2 34438094
2025 Case report: Severe arrhythmogenic cardiomyopathy in a young girl with compound heterozygous DSG2 and MYBPC3 variants with a 6-year follow-up. Frontiers in genetics 1 40115818
2025 Biventricular Dysfunction in Knock-in Mice With Dsg2 Variants Specific for Japanese Arrhythmogenic Right Ventricular Cardiomyopathy. Circulation journal : official journal of the Japanese Circulation Society 1 40887256
2025 Inflammatory Features in Homozygous DSG2 Cardiomyopathy Mimicking Cardiac Sarcoidosis. JACC. Case reports 1 40956261
2024 Case report: Additional variants induced sudden cardiac death among pediatric ACM with DSG2 homozygous mutant genotype: a report of three cases. Frontiers in genetics 1 39253717
2024 Four cardiomyopathy patients with a heterozygous DSG2 p.Arg119Ter variant. Human genome variation 1 39706847
2023 Toward the understanding of DSG2 and CD46 interaction with HAdV-11 fiber, a super-complex analysis. Journal of virology 1 37921471
2022 [Silencing CD46 and DSG2 in host A549 cells inhibits entry of human adenovirus type 3 and type 7 and reduces interleukin-8 release]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 1 36210707
2021 [Analysis of DSG2, TTN and GATA4 gene variants in patients with Brugada syndrome from Henan]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 33974263
2019 Correction to: Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion. Cellular and molecular life sciences : CMLS 1 31292664
2026 TROP2 Promotes Tumor Cell Migration through Downregulation of DSG2 Revealed by Super-Resolution Fluorescence Imaging. Analytical chemistry 0 41531208
2026 Desmoglein 2 (DSG2)-knockout human respiratory epithelial cell model to study species B adenovirus receptor usage. Virologica Sinica 0 41679545
2026 DSG2+ Cancer Stem Cells Co-Located With FAP+ Myofibroblasts in the Tumor Boundary That Determines the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41691490
2026 DSG2-Directed CAR-T Cells Safely and Universally Eliminate Solid Tumors. Research square 0 41727586
2026 Targeting PPAR-γ Reduces Fibrosis and Arrhythmogenic Remodeling in DSG2-Linked Arrhythmogenic Cardiomyopathy. Circulation. Genomic and precision medicine 0 41980193
2026 CD46 and DSG2 synergistically mediate human adenovirus type 7 infection. Journal of virology 0 41989164
2025 SFRP4 Knockdown Attenuates Dsg2-Deficient Arrhythmogenic Cardiomyopathy by Down-Regulating TGF-β and Smad3. Biochemical genetics 0 40019607
2025 Generation of the human iPSC line UNIPDi006-A from a patient with arrhythmogenic cardiomyopathy carrying the DSG2 c.1672C > T pathogenic variant. Stem cell research 0 40106965
2025 Oxymatrine ameliorates ulcerative colitis via improving epithelial barrier function through targeting DSG2. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41076918
2025 Right Atrial Myxoma in a Young Patient with a DSG-2 Genetic Mutation: A Case Report. Case reports in oncology 0 41158880
2025 The oncogenic role of lncRNA DSG2-AS1 and its functional link to SGK1 in laryngeal squamous cell carcinoma. Discover oncology 0 41350507
2025 Hirudin suppresses hematogenous metastasis by targeting desmosome junction transition in circulating tumor cell clusters via HIF-1α-DSG2 signaling. Experimental & molecular medicine 0 41381723
2024 Ser194Leu DSG2 mutation, associated with arrhythmogenic left ventricular cardiomyopathy and ventricular tachycardia. Pacing and clinical electrophysiology : PACE 0 38375917