Recombinant Human Desmoglein-1 (DSG1), partial Protein

Function

A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:19717567). Promotes differentiation of keratinocytes via interaction with ERBIN. Reduces activation of RAS/ERK signaling pathways in keratinocytes via promoting ERBIN localization to the cell membrane and its interaction with SHOC2, this competitively reduces the formation of RAS-SHOC2 ERK-activating complexes (PubMed:23524970). Mediates the interaction between the desmosome and COP9 signalosome complex (CSN) protein complex (PubMed:28891468). As a result of this interaction, promotes keratinocyte differentiation via deneddylation of EGFR resulting in a reduction in EGFR protein stabilization and translocation away from the cell membrane (PubMed:28891468). Critical for epidermal integrity and barrier function of the skin (By similarity). Required for esophageal epithelial barrier integrity and correct intercellular spacing in differentiated esophageal epithelium (PubMed:24220297). Required for recovery of epidermal architecture and correct expression of differentiation markers following UVB exposure (PubMed:24594668). May also be required for OCLN involvement in tight junctions (By similarity)

Subcellular Location

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

Disease Association

Palmoplantar keratoderma 1, striate, focal, or diffuse (PPKS1) : A dermatological disorder characterized by thickening of the skin on the palms and soles, and longitudinal hyperkeratotic lesions on the palms, running the length of each finger. [The disease is caused by variants affecting the gene represented in this entry] | Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE (EPKHE) : A syndrome characterized by severe dermatitis, multiple allergies and metabolic wasting. Clinical features include erythroderma, yellowish papules and plaques arranged at the periphery of the palms, along the fingers and over weight-bearing areas of the feet, skin erosions and scaling, and hypotrichosis. Additionally, patients manifest severe food allergies, elevated immunoglobulin E (IgE) levels and recurrent infections with marked metabolic wasting. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in all suprabasal layers of the epidermis, with the highest expression seen in the granular layer (at protein level). Expressed in the suprabasal esophageal epithelium (at protein level) (PubMed:24220297)

Subunit

(Microbial infection) Interacts with Staphylococcus aureus protein SdrD; this interaction increases S.aureus adherence to keratinocytes

• Wheeler G.N. et al. Desmosomal glycoprotein DGI, a component of intercellular desmosome junctions, is related to the cadherin family of cell adhesion molecules. — Proc. Natl. Acad. Sci. U.S.A. (1991)
• Nilles L.A. et al. Structural analysis and expression of human desmoglein: a cadherin-like component of the desmosome. — J. Cell Sci. (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)
• Rickman L. et al. N-terminal deletion in a desmosomal cadherin causes the autosomal dominant skin disease striate palmoplantar keratoderma. — Hum. Mol. Genet. (1999)
• Hanakawa Y. et al. Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded skin syndrome. — J. Clin. Invest. (2002)
• 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)