Affinage

DSG2

Desmoglein-2 · UniProt Q14126

Length
1118 aa
Mass
122.3 kDa
Annotated
2026-06-09
78 papers in source corpus 33 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DSG2 is the ubiquitously expressed desmosomal cadherin that forms the adhesive core of desmosomes in simple and stratified epithelia, myocardium, and other desmosome-bearing tissues (PMID:8143788, PMID:8641550). Its extracellular domains mediate Ca2+-dependent homophilic strand-swap dimerization, whose free-energy landscape reflects a high activation barrier characteristic of strand-swap binding (PMID:29062102), and it also engages in heterophilic trans interactions with DSG3 and with P-cadherin, the latter providing strand-swap dimers that facilitate desmosome assembly (PMID:33193387). Progressive ordering of the DSG2 ectodomain accompanies the maturation and strengthening of assembling desmosomes (PMID:38566311). The cytoplasmic tail couples to the desmosomal plaque through high-affinity binding to plakoglobin (JUP) via the fourth armadillo repeat (PMID:8749329), and in cardiomyocytes DSG2 associates with plakophilin-2, connexin 43, and plakin cytolinkers in a tension-dependent interactome. Beyond adhesion, DSG2 functions as a signaling hub: it activates EGFR through a c-Src– and caveolin-1–dependent lipid-raft mechanism, driving STAT3, PI3K/AKT, MEK-MAPK, and NF-κB signaling that promotes proliferation, apoptosis resistance, and tumorigenesis (PMID:26918609, PMID:17284515), with EGFR engagement occurring through direct heterotypic surface binding that can also direct EGFR toward junctional adhesion rather than proliferation (PMID:29980799); phosphorylation of DSG2 at Thr730 by PRKD2 further amplifies EGFR/Src/AKT/ERK signaling to promote carcinoma invasion (PMID:38411280). In the heart, loss-of-function and missense DSG2 mutations disrupt desmosome integrity and force transmission within and between sarcomeres (PMID:39706847), causing arrhythmogenic/dilated cardiomyopathy with myocyte necrosis as the initiating injury (PMID:19635863); misfolded mutant DSG2 is recognized by BiP and triggers PERK-ATF4–driven TGF-β1 fibrosis (PMID:39227800), while DSG2 deficiency impairs mTOR-4EBP1-PPARα–dependent fatty acid β-oxidation and drives STAT3/SMAD3- and PPARγ/β-catenin-mediated lipid accumulation and fibrosis (PMID:36815030, PMID:36291052, PMID:41980193). DSG2 additionally serves as a cell-surface receptor for species B human adenoviruses (HAdV-B3/B7/B14/B55) (PMID:22457526, PMID:34224109) and, through sialylated N-glycans, as a counter-receptor for Siglec-9 that suppresses macrophage phagocytosis of tumor cells (PMID:39813162).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1994 High

    Establishing DSG2 as the ubiquitous desmoglein isoform defined which tissues depend on it for desmosomal adhesion, distinguishing it from the restricted DSG1/DSG3.

    Evidence cDNA cloning, sequence determination, and immunocytochemistry across multiple tissues

    PMID:8143788 PMID:8641550

    Open questions at the time
    • Does not address adhesive binding mechanism or signaling roles
    • Tissue distribution alone does not establish function
  2. 1995 High

    Mapping the plakoglobin-binding determinant resolved how the DSG2 cytoplasmic tail couples to the desmosomal plaque.

    Evidence In vitro binding assays with recombinant plakoglobin deletion mutants

    PMID:8749329

    Open questions at the time
    • Affinity quantification incomplete
    • Does not address plakophilin or desmoplakin linkage in vivo
  3. 2009 High

    A dominant-negative cardiac DSG2 mutant model showed that DSG2 dysfunction causes arrhythmogenic cardiomyopathy and identified myocyte necrosis as the initiating lesion.

    Evidence Cardiac-specific DSG2 mutant transgenic mice with dose-dependent phenotyping and human tissue correlation

    PMID:19635863

    Open questions at the time
    • Molecular trigger of necrosis not defined
    • Link between adhesion loss and electrical instability unresolved
  4. 2016 High

    Connecting DSG2 to EGFR through lipid-raft remodeling reframed DSG2 as a signaling platform rather than a purely structural adhesion molecule.

    Evidence siRNA knockdown/overexpression, sucrose fractionation, STED imaging, and cholesterol depletion in A431 cells

    PMID:17284515 PMID:26918609 PMID:29980799

    Open questions at the time
    • Stoichiometry of DSG2-EGFR-Cav1-Src complex unresolved
    • How adhesion vs proliferation signaling outputs are selected remains incomplete
  5. 2017 High

    Single-molecule force spectroscopy showed ARVC mutations weaken DSG2 homophilic binding kinetically without disrupting the strand-swap motif, linking biophysical adhesion defects to disease.

    Evidence AFM single-molecule force spectroscopy and dispase dissociation assays with WT/mutant DSG2

    PMID:29062102

    Open questions at the time
    • How altered binding kinetics translate to tissue-level failure not shown
    • Heterophilic binding contributions not tested here
  6. 2020 High

    Demonstrating heterophilic DSG2-DSG3 catch-bond binding revealed a partner-mixing mechanism that can buffer adhesion loss, with relevance to pemphigus.

    Evidence Cell-free AFM single-molecule binding and IP with autoantibody inhibition

    PMID:33193387 PMID:33387800

    Open questions at the time
    • In vivo significance of heterophilic rescue not established
    • Quantitative contribution to tissue cohesion unclear
  7. 2012 High

    Identifying DSG2 as a species B adenovirus receptor explained tropism of HAdV-B and established a non-adhesive surface function.

    Evidence Human DSG2 transgenic mice and GFP-reporter HAdV-B transduction; later gain/loss-of-function in cell lines for HAdV-B55

    PMID:22457526 PMID:34224109

    Open questions at the time
    • Receptor-binding interface on DSG2 not mapped
    • Whether viral binding perturbs desmosomal adhesion not addressed
  8. 2022 High

    Cardiac-specific DSG2 knockouts uncovered metabolic and fibrotic mechanisms—impaired mTOR-PPARα fatty acid oxidation and STAT3/SMAD3-driven fibrosis—linking adhesion loss to heart failure.

    Evidence CS-Dsg2-/- mice with rapamycin, mTOR/4EBP1 overexpression, fenofibrate, and AAV9-Pparα rescue

    PMID:36291052 PMID:36815030

    Open questions at the time
    • How loss of a junctional protein controls metabolic transcription unresolved
    • Causal ordering of metabolic vs structural defects unclear
  9. 2024 High

    Knock-in models defined a proteostatic disease mechanism: misfolded DSG2 mutant engages BiP and triggers PERK-ATF4-TGF-β1 fibrosis, and PRKD2 phosphorylation at Thr730 was identified as a signaling-amplifying modification.

    Evidence Dsg2 F536C knock-in mice with BiP co-IP and PERK-ATF4 inhibition; PRKD2 kinase-substrate identification by MS and phosphomutant assays

    PMID:38411280 PMID:39227800

    Open questions at the time
    • Generality of ER-stress mechanism across DSG2 mutations not established
    • Physiological substrates and regulation of T730 phosphorylation incompletely defined
  10. 2025 High

    DSG2 was established as a sialic-acid-dependent Siglec-9 counter-receptor functioning as a 'don't eat me' signal, and P-cadherin was shown to nucleate desmosome assembly via strand-swap dimers with DSG2.

    Evidence Proximity labeling/CRISPR screen and phagocytosis assays for Siglec-9; single-molecule AFM, mutagenesis, and rescue assays for P-cadherin (preprint)

    PMID:39813162

    Open questions at the time
    • Structural basis of Siglec-9 glycan recognition not defined
    • P-cadherin findings remain preprint and require peer review

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dual structural and signaling functions of DSG2 are integrated and selectively engaged across epithelial homeostasis, cancer, cardiac mechanotransduction, and immune evasion remains unresolved.
  • No unified structural model of the DSG2 adhesive-signaling complex
  • Mechanism coupling junctional adhesion state to transcriptional/metabolic output undefined
  • Whether signaling roles are conserved across tissues unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 4 GO:0060089 molecular transducer activity 3 GO:0001618 virus receptor activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-162582 Signal Transduction 3 R-HSA-397014 Muscle contraction 2
Partners
CDH3DSG3EGFRJUPPKP2PRKD2SIGLEC9TROP2
Complex memberships
desmosomeintercalated disc

Evidence

Reading pass · 37 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 including simple epithelia, myocardium, and non-epithelial tissues; unlike DSG1 and DSG3, DSG2 is the largest family member (1069 aa) and is the only DSG isoform detected in many tissues such as simple epithelia and myocardium. cDNA cloning, amino acid sequence determination, Northern/Southern blotting, immunocytochemistry Experimental cell research High 8143788
1996 DSG2 protein localizes to desmosomes in all desmosome-containing tissues (stratified and simple epithelia, myocardium, lymph node follicles); antibodies against the extracellular domain of DSG2 also react with 'half-desmosomes' on the surface of uncoupled epithelial cells. In stratified squamous epithelia, DSG2 is restricted to the basal cell layer. Immunocytochemistry with monoclonal and polyclonal antibodies against N-terminal extracellular and C-terminal cytoplasmic domains; immunoelectron microscopy Differentiation; research in biological diversity High 8641550
1992 The DSG2 gene was mapped to human chromosome 18, co-localizing with DSG1. PCR-based chromosomal assignment assay Genomics Medium 1612610
1995 The fourth armadillo repeat of plakoglobin is required for its high-affinity binding to the cytoplasmic domain of DSG2 (and E-cadherin and APC); a 12-repeat plakoglobin lacking the fourth armadillo repeat binds DSG2 with lower affinity than the full 13-repeat form. In vitro binding assay using bacterially expressed recombinant plakoglobin constructs; deletion mutagenesis Journal of biochemistry High 8749329
2007 Suprabasal overexpression of DSG2 in transgenic mouse epidermis causes epidermal hyperplasia, increased keratinocyte proliferation, and apoptosis resistance through activation of multiple signaling pathways including PI3K/AKT, MEK-MAPK, STAT3, and NF-κB; this requires EGFR activation and NF-κB activity for anchorage-independent survival. Involucrin-promoter-driven DSG2 transgenic mice; cultured keratinocytes; EGFR inhibition; NF-κB inhibition; chemical carcinogenesis assays Journal of cell science High 17284515
2009 Cardiac overexpression of dominant-negative DSG2-N271S (mouse equivalent of human N266S) in transgenic mice causes ARVC features including biventricular dilatation, ventricular arrhythmias, and sudden death; myocyte necrosis was identified as the key initiator of myocardial injury, preceding inflammation, calcification, and fibrous replacement. Transgenic mouse model with cardiac-specific DSG2 mutant overexpression; histopathology; electrophysiology; multiple transgene expression levels demonstrating dose-dependence The Journal of experimental medicine High 19635863
2016 DSG2 activates EGFR signaling via a c-Src and Caveolin-1 (Cav1)-dependent mechanism using lipid rafts as signaling platforms; DSG2 overexpression displaces Cav1, EGFR, and c-Src from light-density lipid raft fractions, and DSG2 knockdown abrogates EGFR, c-Src, and STAT3 activation in response to EGF, increasing cell proliferation and migration through EGFR/c-Src. siRNA knockdown, sucrose density fractionation, STED super-resolution imaging, overexpression in A431 cells, cholesterol chelation (MβCD), proliferation and migration assays Oncotarget High 26918609
2018 DSG2 directly interacts with EGFR and undergoes heterotypic binding via its extracellular domain on the surface of living enterocytes; DSG2 is required for EGFR localization at intercellular junctions and for Src-mediated EGFR activation, directing EGFR signaling towards cell adhesion rather than proliferation. DSG2-deficient enterocytes show impaired barrier properties and increased proliferation. Atomic force microscopy (AFM) on living cells, co-immunoprecipitation, Src/EGFR inhibitors, DSG2 knockout/knockdown, transepithelial resistance measurement Cellular and molecular life sciences : CMLS High 29980799
2017 ARVC-associated DSG2 mutations (tested by single-molecule force spectroscopy) alter the kinetics and thermodynamics of DSG2 homophilic binding without directly affecting the strand-swapping binding motif; the free energy landscape of Dsg2 dimerization shows a high activation barrier consistent with strand-swap binding, and mutations significantly reduce homophilic binding strength in a cell dissociation assay. Single-molecule force spectroscopy (AFM), Jarzynski's equality thermodynamic analysis, dispase cell dissociation assay with DSG2 WT and mutant overexpressing HT1080 cells Scientific reports High 29062102
2019 ARVC-associated DSG2 mutations alter the N-glycosylation pattern of desmoglein-2 protein even when the mutations do not directly affect N-glycosylation consensus sequences, indicating complex molecular interactions between DSG2 mutations and N-glycosylations. De-glycosylation assays, lectin blot analysis, genetic inhibition of glycosylation, in vitro cell transfection Journal of molecular and cellular cardiology Medium 30885746
2010 Ectopic superficial expression of DSG2 (via involucrin promoter transgene) reduces the extent of epidermal blister formation induced by pemphigus foliaceus antibodies and staphylococcal exfoliative toxin ETA, and enhances retention of DSG1 at cell borders, supporting a direct role for DSG2 in epithelial adhesion. Neonatal transgenic mouse injection with PF IgG or ETA; histology; immunofluorescence for DSG1 isoforms Dermatology research and practice Medium 20631906
2012 Human DSG2 functions as a receptor for adenovirus species B (HAdV-B3, B7, B14) and mediates efficient viral transduction of epithelial cells; transgenic mice expressing human DSG2 at physiological levels show hDSG2-dependent transduction of bronchial/alveolar epithelial cells (intranasal) and intestinal/colon epithelial cells (intravenous) by HAdV-B3. hDSG2 transgenic mouse generation; GFP-expressing HAdV-B3 vector administration; qRT-PCR and immunohistochemistry for GFP Journal of virology High 22457526
2021 Human DSG2 is a receptor for HAdV-B55; 3T3 rodent cells (which do not express human DSG2) became susceptible to HAdV-B55 infection after transfection with pcDNA3.1-DSG2; siRNA knockdown of hDSG2 in A549 cells impaired infection by HAdV-B3, B14, and B55; immunofluorescence confocal microscopy confirmed Cy3-conjugated HAdV-B55 enters cells via binding DSG2. Heterologous expression (pcDNA3.1-DSG2 in 3T3 cells), siRNA knockdown, immunofluorescence confocal microscopy Virologica Sinica High 34224109
2006 UV radiation down-regulates DSG2 in human lens epithelial cells via a pathway involving EGFR transactivation, Rac2 translocation, and NADPH oxidase-dependent reactive oxygen species generation. Cultured human lens epithelial cells; UV/H2O2 treatment; ROS measurement; EGFR activation assay; Rac2 translocation assay; NADPH oxidase inhibition International journal of molecular medicine Medium 16820949
2018 DSG2 regulates β-catenin/Slug-mediated epithelial-to-mesenchymal transition to maintain self-renewal and pluripotency in human pluripotent stem cells; depletion of DSG2 markedly decreased hPSC proliferation and pluripotency marker expression, and DSG2-negative hPSC populations show suppressed embryoid body and teratoma formation. Monoclonal antibody generation and target identification; siRNA knockdown; pluripotency marker analysis; embryoid body and teratoma formation assays; β-catenin/Slug pathway analysis Stem cell reports Medium 29910125
2020 DSG2 undergoes heterophilic binding with DSG3; DSG2-DSG3 heterophilic interactions show binding frequency, strength, Ca2+-dependency, and catch-bond behavior comparable to homophilic Dsg3-Dsg3 interactions, but with longer lifetime than homophilic Dsg2-Dsg2 interactions. PV autoantibodies inhibit homophilic DSG3 interactions more strongly than heterophilic DSG2-DSG3 interactions, suggesting heterophilic binding as a rescue mechanism. Immunoprecipitation, cell-free atomic force microscopy (AFM), DSG3-deficient keratinocytes, pemphigus autoantibody inhibition experiments, anti-DSG2 inhibitory antibody Frontiers in immunology High 33193387
2020 DSG2 knockdown in anaplastic thyroid cancer cells increases cell migration and invasion through the c-Met/Src/Rac1 signaling axis without altering EMT-related molecule expression; specific c-Met inhibition blocks the motility increase caused by DSG2 depletion, placing DSG2 upstream of c-Met-dependent motility control. shRNA DSG2 knockdown, migration/invasion assays in vitro, in vivo distant metastasis models, c-Met/Src/Rac1 pathway analysis, c-Met inhibitor treatment Endocrine-related cancer Medium 33022637
2018 DSG2 overexpression in basal keratinocytes (K5 promoter transgenic mice) accelerates full-thickness wound closure, increases wound-adjacent keratinocyte proliferation, and induces increased secretion and proteolytic processing of urokinase-type plasminogen activator receptor (uPAR); uPAR upregulation correlates with increased laminin-332 in transgenic skin upon wounding. K5-promoter DSG2 transgenic mice, wound healing assay, antibody profiler secretome array, immunohistochemistry for uPAR and laminin-332 The Journal of investigative dermatology Medium 29753032
2015 DSG2 regulates cystatin A (CSTA) expression; siRNA/shRNA knockdown of DSG2 reduces CSTA expression, while siRNA knockdown of CSTA leads to cytoplasmic mislocalization of DSG2, perturbed cytokeratin 14 staining, and reduced desmoplakin levels under mechanical stretching. Combined knockdown of DSG2 and CSTA has synergistic loss of cell adhesion in dispase assays. siRNA and shRNA knockdown, microarray and qPCR, immunoblotting, immunohistochemistry, dispase-based cell adhesion assay PloS one Medium 25785582
2022 In Dsg2-deficient (CS-Dsg2-/-) cardiac-specific knockout mice, cardiac lipid accumulation and heart failure result from impaired mTOR-4EBP1-PPARα-dependent fatty acid β-oxidation; rapamycin worsened the phenotype, while mTOR and 4EBP1 overexpression rescued FA β-oxidation. Fenofibrate or AAV9-Pparα treatment restored cardiac function. Cardiac-specific Dsg2 knockout mice, rapamycin treatment, AAV9-mTOR/4EBP1 overexpression, fenofibrate/AAV9-Pparα treatment, lipid staining, echocardiography Acta pharmaceutica Sinica. B High 36815030
2022 Loss of DSG2 in cardiac-specific knockout mice leads to increased cardiac fibrosis via PPARα deficiency and hyperactivation of STAT3 and SMAD3; Stat3 siRNA reduced fibrotic markers; PPARα activation by fenofibrate or AAV9-Pparα reduced cardiac fibrosis and decreased phosphorylation of STAT3, SMAD3, and AKT. CS-Dsg2-/- mice, Masson staining, Western blot, Stat3 siRNA in HL-1 cells, fenofibrate treatment, AAV9-Pparα administration Cells Medium 36291052
2024 DSG2-F531C (F536C in mice) mutant protein undergoes misfolding, is recognized by BiP in the endoplasmic reticulum, triggering ER stress and activation of PERK-ATF4 signaling; increased ATF4 promotes TGF-β1 expression in cardiomyocytes, which activates cardiac fibroblasts via paracrine signaling leading to cardiac fibrosis. PERK-ATF4 pathway inhibition attenuated fibrosis in Dsg2 F536C/F536C knock-in mice. Dsg2 F536C knock-in mice (CRISPR), neonatal and adult mouse ventricular myocytes, transcriptomic analysis, mass spectrometry, BiP co-immunoprecipitation, PERK-ATF4 inhibitor treatment BMC medicine High 39227800
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. Interactome/co-IP analysis plus mass spectrometry identification of PRKD2 as DSG2 kinase; T730A/D phosphomutant functional assays; ESCC cell migration/invasion assays; Western blot for downstream signaling The Journal of pathology High 38411280
2022 TROP2 interacts with DSG2 in gastric cancer cells (identified by co-immunoprecipitation and mass spectrometry); TROP2 overexpression decreases DSG2 levels and desmosome adhesion, promoting cell invasion and migration through EGFR/AKT and DSG2/plakoglobin/β-catenin pathways. Co-immunoprecipitation with mass spectrometry, TROP2 overexpression/knockdown, cell adhesion assays, electron microscopy of desmosomes, Western blotting of EGFR/AKT and DSG2/PG/β-catenin pathway components Current cancer drug targets Medium 35392784
2024 DSG2 ectodomain organization (measured by fluorescence polarization microscopy) increases gradually over 8 hours during desmosome assembly, coinciding with increasing adhesive strength; a similar increase in ectodomain order occurs in desmosomes assembling at the leading edge of migratory cells during wound healing, indicating that cadherin ectodomain organization is a hallmark of desmosome maturity. Fluorescence polarization microscopy of Dsg2 ectodomain, scratch wound assay, time-course imaging of assembly Cell adhesion & migration Medium 38566311
2021 A DSG2 nonsense mutation (p.S363X) located in the extracellular domain results in absence of the truncated DSG2 protein at the plasma membrane, as demonstrated by in vitro cell transfection experiments; this supports the pathogenic mechanism of loss of membrane-targeted DSG2 in arrhythmogenic cardiomyopathy. In vitro cell transfection, immunofluorescence of plasma membrane localization International journal of molecular sciences Medium 34202524
2025 DSG2 is a dominant counter receptor of Siglec-9 in melanoma cells; the DSG2-Siglec-9 interaction is primarily dependent on sialic acid-bearing N-glycans on DSG2; blocking this trans interaction significantly enhances macrophage phagocytosis of melanoma cells. Proximity labeling combined with CRISPR knockout screening; co-immunoprecipitation; sialic acid manipulation; phagocytosis assays Advanced science High 39813162
2024 Loss of DSG2 in cardiomyocytes leads to reduced contractility; iPSC-CMs carrying a heterozygous truncating DSG2 variant (p.Arg119Ter) showed reduced contractility in microforce testing; immunohistochemical analysis showed reduced desmoglein-2 AND desmoplakin expression, with widened and fragmented desmosomes and widened intercalated disc gaps by electron microscopy. iPSC-CM microforce contractility assay, immunohistochemistry, transmission electron microscopy, endomyocardial biopsy analysis Human genome variation Medium 39706847
2025 DSG2 promotes pancreatic cancer stem cell stemness via an IL-8/CXCR2 axis that activates Wnt/β-catenin signaling; DSG2 knockdown suppressed IL-4 and GM-CSF expression and reduced tumour-associated macrophage niche support. The IL-8/CXCR2-DSG2 interaction promotes gemcitabine resistance. DSG2 knockdown (shRNA), cytokine expression analysis, Wnt/β-catenin pathway analysis, macrophage co-culture, gemcitabine resistance assays Cell death & disease Medium 40615400
2025 In Dsg2-mutant knock-in mice, loss of DSG2 function leads to Z-disc structural defects and increased myosin detachment rate; Ca2+-activated force was reduced in permeabilized left ventricular cardiac muscle bundles but preserved in isolated permeabilized cardiomyocytes, demonstrating that DSG2 is required for force transmission between as well as within sarcomeres. Homozygous Dsg2 mutant knock-in mice; permeabilized cardiac muscle bundle and isolated cardiomyocyte mechanical assays; electron microscopy of Z-discs bioRxivpreprint Medium
2025 Pathogenic autoantibodies from ACM patients bind to DSG2 in hiPSC-CMs, cleave DSG2, and reduce DSG2 interaction at the molecular level; these antibodies activate GSK-3β (upstream of p38MAPK), leading to phosphorylation and junctional loss of β-catenin, causing loss of cardiomyocyte cohesion. GSK-3β inhibition rescued antibody-induced loss of cohesion. hiPSC-CM cohesion assays, Western blotting for DSG2 cleavage, GSK-3β/p38MAPK/β-catenin pathway analysis, GSK-3β inhibitor rescue experiments bioRxivpreprint Medium
2025 P-cadherin (Pcad) facilitates desmosome assembly by forming heterophilic trans strand-swap dimers with DSG2 on opposing cells; the interaction requires flexibility of the hinge on the swapped β-strands (terminating in conserved Trp residues); strand-swap deficient Pcad fails to rescue desmosome assembly in cells lacking classical cadherins, while strand-swap competent Pcad rescues assembly. Single-molecule AFM, super-resolution and confocal imaging, mutagenesis of strand-swap residues, atomistic simulations, cell-based desmosome assembly rescue assays bioRxivpreprint Medium
2025 The DSG2 interactome in primary neonatal cardiomyocytes (identified by proximity labeling and quantitative mass spectrometry) includes over 300 proteins; connexin 43 and plakin family cytolinker proteins are unique to DSG2 (vs N-cadherin); plakoglobin (JUP) and plakophilin-2 (PKP2) are the most abundant shared proteins between DSG2 and N-cadherin interactomes. PKP2 membrane recruitment in cardiomyocytes is tension-dependent. Proximity labeling (BioID or similar) combined with quantitative mass spectrometry in primary neonatal cardiomyocytes bioRxivpreprint Medium
2024 DSG2 interacts with c-MYC (demonstrated by co-immunoprecipitation) in cervical cancer cells; DSG2 overexpression combined with c-MYC inhibition significantly decreases ADAM17 expression, cell proliferation, and migration compared to DSG2 overexpression alone, indicating DSG2 regulates ADAM17 expression through c-MYC interaction. Co-immunoprecipitation, c-MYC inhibitor treatment, ADAM17 qPCR and Western blot, cell proliferation and migration assays Cancer management and research Low 38948682
2025 DSG2 knockdown in lung adenocarcinoma cells enhances gemcitabine-induced apoptosis by downregulating the NFκB/STAT3/PTX3 signaling axis; adding recombinant PTX3 protein to DSG2 knockdown cells restores STAT3 activation and reduces gemcitabine efficacy, demonstrating DSG2 mediates gemcitabine resistance through PTX3. DSG2 siRNA knockdown, gemcitabine treatment, apoptosis assays, NFκB/STAT3/PTX3 pathway Western blot, recombinant PTX3 rescue experiment Biochimica et biophysica acta. Molecular basis of disease Medium 40316058
2025 Oxymatrine (OMT) directly binds to DSG2 (confirmed by CETSA, DARTS, and microscale thermophoresis), stabilizing DSG2 and inhibiting caspase-8-dependent DSG2 cleavage; DSG2 knockdown diminishes the therapeutic effects of OMT in intestinal epithelial cells, demonstrating that OMT's barrier-protective effects require DSG2. CETSA, DARTS, microscale thermophoresis binding assays; caspase-8 activity assay; lentiviral Dsg2 knockdown; intestinal epithelial barrier function assays Phytomedicine Medium 41076918
2025 In Dsg2 knock-in mice with the F531C mutation, DSG2 deficiency leads to nuclear accumulation of β-catenin and PPAR-γ, promoting triacylglycerol biosynthesis, oxidative stress, cardiomyocyte death, and calcium-handling abnormalities; epicardial epithelial-to-mesenchymal transition and paracrine fibroblast activation via IL-6 and PDGF-BB contribute to fibrotic remodeling. PPAR-γ antagonist GW9662 treatment attenuated these features. CRISPR/Cas9 knock-in mice (Dsg2 F531C), transcriptomic profiling, in vitro cardiomyocyte/fibroblast assays, ex vivo optical mapping, GW9662 treatment, immunostaining Circulation. Genomic and precision medicine High 41980193

Source papers

Stage 0 corpus · 78 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 168 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 53 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 46 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
2018 Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion. Cellular and molecular life sciences : CMLS 29 29980799
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
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 20 30885746
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 19 36815030
2017 Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2. BMC medical genetics 19 28818065
2025 Natural History and Clinical Outcomes of Patients With DSG2/DSC2 Variant-Related Arrhythmogenic Right Ventricular Cardiomyopathy. Circulation 17 40123482
2019 A common indel polymorphism of the Desmoglein-2 (DSG2) is associated with sudden cardiac death in Chinese populations. Forensic science international 17 31220685
2022 Activation of PPARα Ameliorates Cardiac Fibrosis in Dsg2-Deficient Arrhythmogenic Cardiomyopathy. Cells 16 36291052
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
2021 Desmoglein 2 (DSG2) Is A Receptor of Human Adenovirus Type 55 Causing Adult Severe Community-Acquired Pneumonia. Virologica Sinica 15 34224109
2010 Superficial dsg2 expression limits epidermal blister formation mediated by pemphigus foliaceus antibodies and exfoliative toxins. Dermatology research and practice 15 20631906
2020 Dsg2-mediated c-Met activation in anaplastic thyroid cancer motility and invasion. Endocrine-related cancer 14 33022637
2018 Enhancement of Cutaneous Wound Healing by Dsg2 Augmentation of uPAR Secretion. The Journal of investigative dermatology 13 29753032
2024 Hyperactivation of ATF4/TGF-β1 signaling contributes to the progressive cardiac fibrosis in Arrhythmogenic cardiomyopathy caused by DSG2 Variant. BMC medicine 12 39227800
2023 Molecular insight into arrhythmogenic cardiomyopathy caused by DSG2 mutations. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 12 37696084
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
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
2022 Properties of Adenovirus Vectors with Increased Affinity to DSG2 and the Potential Benefits of Oncolytic Approaches and Gene Therapy. Viruses 9 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 9 30129429
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
2024 Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression. The Journal of pathology 8 38411280
2015 Arrhythmogenic right ventricular cardiomyopathy with left ventricular involvement: a novel splice site mutation in the DSG2 gene. Cardiology 8 25660657
2024 Dsg2 ectodomain organization increases throughout desmosome assembly. Cell adhesion & migration 7 38566311
2019 Distal myopathy induced arrhythmogenic right ventricular cardiomyopathy in a pedigree carrying novel DSG2 null variant. International journal of cardiology 7 31653443
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) 6 39813162
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
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 5 39597880
2023 Misdiagnosed myocarditis in arrhythmogenic cardiomyopathy induced by a homozygous variant of DSG2: a case report. Frontiers in cardiovascular medicine 5 37288269
2018 PKP2 and DSG2 genetic variations in Latvian arrhythmogenic right ventricular dysplasia/cardiomyopathy registry patients. Anatolian journal of cardiology 4 30391969
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
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
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 2 39253717
2023 Toward the understanding of DSG2 and CD46 interaction with HAdV-11 fiber, a super-complex analysis. Journal of virology 2 37921471
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 Ser194Leu DSG2 mutation, associated with arrhythmogenic left ventricular cardiomyopathy and ventricular tachycardia. Pacing and clinical electrophysiology : PACE 1 38375917
2024 Four cardiomyopathy patients with a heterozygous DSG2 p.Arg119Ter variant. Human genome variation 1 39706847
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
2026 TGFA promotes the development of cervical cancer via interacting with DSG2. Cell cycle (Georgetown, Tex.) 0 42154444
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

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