DSP
Domain
The N-terminal region is required for localization to the desmosomal plaque and interacts with the N-terminal region of PKP1.
Function
A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:25733715). Critical for cell-cell adhesion in early stage blastocysts and progression through proamniotic cavity formation (By similarity). Not required for preimplantation morphogenic process in blastocysts (By similarity). Required for keratin filament anchoring at the desmosome junction and subsequent organization of the keratin intermediate filament network within the cytoplasm (By similarity). Required for anchoring of desmosomes to the microtubule architecture, via its interaction with NIN (By similarity). Plays a key role in adhesion and organization of the dermal epithelial barrier (By similarity). Critical for the maintenance of the neural tube structure following formation and organization of the neuroepithelium (By similarity). Facilitates outgrowth and repair of motor neuron fibers in regenerating axons following injury, probably by promoting recruitment of a complex containing DSP, CDH2, VIM and JUP to the outgrowth tips (By similarity). Required for the normal formation of the heart, also required for development of vascular capillary structures and intact endothelial cell barriers (By similarity). Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundance (By similarity). Maintains cardiac rhythmicity by ensuring correct cell-cell adhesion within the sinoatrial node, via stabilization of protein components of both desmosome and Gap junctions (By similarity). Involved in maintaining the protein stability and recruitment of GJA1 to functional gap junctions, via inhibition of KRAS-mediated MAPK1/MAPK3 phosphorylation of GJA1 (By similarity). Required for the survival and maintenance of germ cells in the gonads during embryonic development (By similarity). Binds to telomere DNA (via C-terminus) and acts to prevent telomere damage and maintain telomere length via its interaction with TRF2 (PubMed:31595153).
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.
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
Methylation by PRMT1 promotes GSK3B-mediated phosphorylation cascade of multiple serine residues at the C-terminus resulting in trafficking to desmosome cell-cell junctions.
Phosphorylation by GSK3B occurs sequentially from Ser-2849 along multiple serine residue at the C-terminus. Hyperphosphorylation by GSK3B results in recruitment to desmosome cell-cell junction and promotion of intercellular adhesion (PubMed:25733715). Phosphorylation at Ser-2849 increases association with intermediate filament cytokeratin, potentially facilitating interaction between desmosome junctions and intermediate filament architecture (PubMed:33596089).
Sequence Similarities
Belongs to the plakin or cytolinker family.
Tissue Specificity
Expressed in oral mucosa (at protein level) (PubMed:30479852). Expressed in arrector pili muscle (at protein level) (PubMed:29034528). Expressed in the heart in the heart (at protein level) (PubMed:18662195).
Isoform DPI
Apparently an obligate constituent of all desmosomes.
Isoform DPII
Resides predominantly in tissues and cells of stratified origin.
Cellular localization
- Cell projection
- Axon
- Cell junction
- Desmosome
- Cell membrane
- Cytoplasm
- Nucleus
- Localizes to desmosome precursor particles in the cytoplasm (PubMed:25208567). Localizes to the cytoplasm in undifferentiated keratinocytes however becomes localizes to both lateral and tricellular cell-cell contacts as differentiation progresses and as epithelial sheet formation completes (By similarity). Localizes to the interface of the cortical keratin network and endodermal cell periphery in developing embryos (By similarity).
Alternative names
Desmoplakin, DP, 250/210 kDa paraneoplastic pemphigus antigen, DSP