DSP

DSP is a protein that anchors intermediate filaments to desmosomal plaques and forms an obligate component of functional desmosomes. Mutations in this gene are the cause of several cardiomyopathies and keratodermas, including skin fragility-woolly hair syndrome.

Full Name

Desmoplakin

Research Area

Major high molecular weight protein of desmosomes. Involved in the organization of the desmosomal cadherin-plakoglobin complexes into discrete plasma membrane domains and in the anchoring of intermediate filaments to the desmosomes.

Biological Process

Adherens junction organization Source: Ensembl
Bundle of His cell-Purkinje myocyte adhesion involved in cell communication Source: BHF-UCL
Cell-cell adhesion Source: GO_Central
Desmosome organization Source: BHF-UCL
Epidermis development Source: ProtInc
Epithelial cell-cell adhesion Source: MGI
Intermediate filament cytoskeleton organization Source: GO_Central
Intermediate filament organization Source: BHF-UCL
Keratinocyte differentiation Source: UniProtKB
Peptide cross-linking Source: UniProtKB
Protein localization to cell-cell junction Source: BHF-UCL
Regulation of heart rate by cardiac conduction Source: BHF-UCL
Regulation of ventricular cardiac muscle cell action potential Source: BHF-UCL
Skin development Source: GO_Central
Ventricular compact myocardium morphogenesis Source: BHF-UCL
Wound healing Source: GO_Central

Cellular Location

Cytoskeleton; Cell membrane; Desmosome. Innermost portion of the desmosomal plaque. Colocalizes with epidermal KRT5-KRT14 and simple KRT8-KRT18 keratins and VIM intermediate filaments network (PubMed:12802069). Localizes at the intercalated disk in cardiomyocytes (By similarity).

Involvement in disease

Keratoderma, palmoplantar, striate 2 (SPPK2):
A dermatological disorder characterized by thickening of the skin on the palms (linear pattern) and the soles (island-like pattern) and flexor aspect of the fingers. Abnormalities of the nails, the teeth and the hair are rarely present.
Cardiomyopathy, dilated, with woolly hair and keratoderma (DCWHK):
An autosomal recessive cardiocutaneous syndrome characterized by a generalized striate keratoderma particularly affecting the palmoplantar epidermis, woolly hair, and dilated left ventricular cardiomyopathy.
Arrhythmogenic right ventricular dysplasia, familial, 8 (ARVD8):
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.
Skin fragility-woolly hair syndrome (SFWHS):
An autosomal recessive genodermatosis characterized by skin fragility with blistering, focal and diffuse palmoplantar keratoderma, hyperkeratotic plaques on the trunk and limbs, and woolly hair with varying degrees of alopecia.
Epidermolysis bullosa, lethal acantholytic (EBLA):
A form of epidermolysis bullosa characterized by severe fragility of skin and mucous membranes. The phenotype is lethal in the neonatal period because of immense transcutaneous fluid loss. Typical features include universal alopecia, neonatal teeth, and nail loss. Histopathology of the skin shows suprabasal clefting and acantholysis throughout the spinous layer, mimicking pemphigus.
Cardiomyopathy, dilated, with woolly hair, keratoderma, and tooth agenesis (DCWHKTA):
A cardiocutaneous syndrome characterized by biventricular dilated cardiomyopathy, hyperkeratosis, woolly hair, palmoplantar keratoderma, and hypo/oligodontia.

PTM

Ser-2849 is probably phosphorylated by a cAMP-dependent protein kinase. Phosphorylation on Ser-2849 probably affects its association with epidermal, simple cytokeratins and VIM intermediate filaments.