DSG3
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:31835537). Required for adherens and desmosome junction assembly in response to mechanical force in keratinocytes (PubMed:31835537). Required for desmosome-mediated cell-cell adhesion of cells surrounding the telogen hair club and the basal layer of the outer root sheath epithelium, consequently is essential for the anchoring of telogen hairs in the hair follicle (PubMed:9701552). Required for the maintenance of the epithelial barrier via promoting desmosome-mediated intercellular attachment of suprabasal epithelium to basal cells (By similarity). May play a role in the protein stability of the desmosome plaque components DSP, JUP, PKP1, PKP2 and PKP3 (PubMed:22294297). Required for YAP1 localization at the plasma membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, PKP1 and YWHAG (PubMed:31835537). May also be involved in the positive regulation of YAP1 target gene transcription and as a result cell proliferation (PubMed:31835537). Positively regulates cellular contractility and cell junction formation via organization of cortical F-actin bundles and anchoring of actin to tight junctions, in conjunction with RAC1 (PubMed:22796473). The cytoplasmic pool of DSG3 is required for the localization of CDH1 and CTNNB1 at developing adherens junctions, potentially via modulation of SRC activity (PubMed:22294297). Inhibits keratinocyte migration via suppression of p38MAPK signaling, may therefore play a role in moderating wound healing (PubMed:26763450).
Involvement in disease
Blistering, acantholytic, of oral and laryngeal mucosa
ABOLM
An autosomal recessive disorder characterized by recurrent, suprabasal acantholytic blisters in the oral and laryngeal mucosa. Skin, conjunctival and genital mucosa, nail folds, and nails are unaffected. Normal structure is observed in the scalp epidermis and hair follicle.
None
The disease may be caused by variants affecting the gene represented in this entry.
Tissue Specificity
Epidermis, tongue, tonsil, esophagus and carcinomas. Expressed in skin and mucosa (at protein level) (PubMed:22294297, PubMed:30528827). Expressed in the basal layer of the outer root sheath of the telogen hair club, specifically at the cell membrane between the apex of the cells and the surrounding hair club (at protein level) (PubMed:9701552). Expression is less abundant between the lateral margins of the outer root sheath basal cells (at protein level) (PubMed:9701552).
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Cell junction
- Desmosome
- Cytoplasm
- Cell junction
- Tight junction
- Cell junction
Alternative names
CDHF6, DSG3, Desmoglein-3, 130 kDa pemphigus vulgaris antigen, Cadherin family member 6, PVA