DSP

Domain

Its association with epidermal and simple keratins is dependent on the tertiary structure induced by heterodimerization of these intermediate filaments proteins and most likely involves recognition sites located in the rod domain of these keratins.

The N-terminal region is required for localization to the desmosomal plaque and interacts with the N-terminal region of plakophilin 1.

The three tandem plakin repeat regions in the C-terminus mediate binding to intermediate filaments.

Function

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.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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.

Sequence similarities

Belongs to the plakin or cytolinker family.

Tissue specificity

Isoform DPI is apparently an obligate constituent of all desmosomes. Isoform DPII resides predominantly in tissues and cells of stratified origin.

Cellular localization

• Cell junction
• Desmosome
• Cytoplasm
• Cytoskeleton
• Cell membrane
• 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).

Alternative names

• Desmoplakin
• DP
• 250/210 kDa paraneoplastic pemphigus antigen
• DSP

Database links

• entrezGene:1832
• omim:125647
• swissprot:P15924

Target type

Proteins

Molecular weight

331774Da