Recombinant Human Desmoglein-3 (DSG3), partial

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)

Subcellular Location

Cell membrane (Single-pass type I membrane protein); Cell junction, desmosome; Cytoplasm; Cell junction, tight junction; Cell junction

Disease Association

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. [The disease may be caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed throughout the basal and spinous layer of the epidermis with weak expression in the granular layer (at protein level) (PubMed:19717567). Expressed in skin and mucosa (at protein level) (PubMed:22294297, PubMed:30528827). Expressed throughout the esophageal mucosa (at protein level) (PubMed:24220297). 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). Also expressed in the tongue, tonsil and esophagus (PubMed:16740002)

Subunit

Homodimer (PubMed:19717567). Part of a complex that contains DSG3, PKP1, YAP1 and YWHAG; the complex is required for localization of DSG3 and YAP1 to the cell membrane in keratinocytes (PubMed:31835537). Interacts with PKP2 (PubMed:11790773). Interacts with CTNND1; the interaction facilitates DSG3 localization and retention at cell-cell junctions (PubMed:18343367). Interacts with CDH1; the interaction is required for CDH1 localization to developing adherens junctions (PubMed:22294297). Interacts with RAC1; the interaction is required for DSG3 translocation to cell-cell junctions, organization of cortical F-actin bundles and actin anchoring at cell-cell junctions (PubMed:22796473). Interacts with DSC3; the interaction may limit the interaction of DSC3 with p38MAPK family members and therefore repress p38MAPK signaling activation (By similarity)

• Amagai M. et al. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. — Cell (1991)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Nusbaum C. et al. DNA sequence and analysis of human chromosome 18. — Nature (2005)
• Koch P.J. et al. Desmoglein 3 anchors telogen hair in the follicle. — J. Cell Sci. (1998)
• Chen X. et al. Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta -catenin signaling. — J. Biol. Chem. (2002)
• Ramachandran P. et al. Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry. — J. Proteome Res. (2006)
• Kanno M. et al. P120-catenin is a novel desmoglein 3 interacting partner: identification of the p120-catenin association site of desmoglein 3. — Exp. Cell Res. (2008)
• Spindler V. et al. Desmocollin 3-mediated binding is crucial for keratinocyte cohesion and is impaired in pemphigus. — J. Biol. Chem. (2009)