DSG2
Domain
Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.
Function
A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:17559062, PubMed:38395410). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Required for proliferation and viability of embryonic stem cells in the blastocyst, thereby crucial for progression of post-implantation embryonic development (By similarity). Maintains pluripotency by regulating epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via interacting with and sequestering CTNNB1 to sites of cell-cell contact, thereby reducing translocation of CTNNB1 to the nucleus and subsequent transcription of CTNNB1/TCF-target genes (PubMed:29910125). Promotes pluripotency and the multi-lineage differentiation potential of hematopoietic stem cells (PubMed:27338829). Plays a role in endothelial cell sprouting and elongation via mediating the junctional-association of cortical actin fibers and CDH5 (PubMed:27338829). Promotes cardiomyocyte cell homeostasis and desmosome junction formation at intercalated disks, as a result plays a role in the maintenance of cardiac conduction and heart chamber integrity (By similarity). Positively regulates pancreatic islet development and maintenance of endothelial cell barrier integrity in the pancreas, therefore involved in the controlled release of insulin from islet cells into the circulation in response to glucose (By similarity). Plays a role in limiting inflammatory infiltration and the apoptotic response to injury in kidney tubular epithelial cells, potentially via its role in maintaining cell-cell adhesion and the epithelial barrier (PubMed:38395410). Acts as a positive modulator of CSK and EGFR activation via sequestering them away from lipid rafts, this is independent of its role in desmosome cell junctions (PubMed:26918609). Also disrupts the localization of CAV1 to lipid rafts resulting in its distribution throughout the cytoplasm (PubMed:26918609).
Involvement in disease
Arrhythmogenic right ventricular dysplasia, familial, 10
ARVD10
A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias.
None
The disease is caused by variants affecting the gene represented in this entry.
Cardiomyopathy, dilated, 1BB
CMD1BB
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Post-translational modifications
Cleaved by CASP3 in response to apoptosis which results in a loss of full length DSG2 at cell-cell adhesion junctions and a decrease in intercellular adhesion.
N-glycosylated; promotes localization to the plasma membrane and cell-cell adhesion junction strength.
Palmitoylated by ZDHHC5 at the plasma membrane.
Tissue Specificity
Expressed in undifferentiated pluripotent stem cells, expression decreases during differentiation (at protein level) (PubMed:29910125). Expressed in hematopoietic stem cells and circulating endothelial progenitor cells, expression decreases upon increasing cell lineage commitment (at protein level) (PubMed:27338829). Expressed on common myeloid progenitors, pro-myelocytes, pro-erythrocytes and B-cell linage progenitors (at protein level). Expression in mature cell types in the bone marrow and mature leukocyte populations is absent (PubMed:27338829). Expressed by foreskin fibroblasts, expression peaks during the early stage of differentiation reprogramming (at protein level) (PubMed:29910125). Expressed by endothelial cells in both arterioles and venules in the cervix (at protein level) (PubMed:27338829). Expressed in pancreatic alpha-cells, beta-cells and exocrine tissue (at protein level) (PubMed:36309486). Expressed in cardiomyocytes (at protein level) (PubMed:31845994, PubMed:38375917). Expressed in kidney tubular epithelial cells (PubMed:38395410).
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Cell junction
- Desmosome
- Cytoplasm
- Localized to intercalated disks in the heart (PubMed:31845994). Localizes to the cytoplasm following cleavage by CASP3 in response to apoptosis (PubMed:17559062). Glycosylation promotes localization to the plasma membrane (PubMed:30885746).
Alternative names
CDHF5, DSG2, Desmoglein-2, Cadherin family member 5, HDGC