ID:DESP_HUMAN DESCRIPTION: RecName: Full=Desmoplakin; Short=DP; AltName: Full=250/210 kDa paraneoplastic pemphigus antigen; 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. SUBUNIT: Homodimer. Interacts with COL17A1 (via cytoplasmic region). Associates (via C-terminal) with KRT5-KRT14 (via rod region), KRT8-KRT18 and VIM intermediate filaments. Interacts with DSC2. SUBCELLULAR LOCATION: Cell junction, desmosome. Cytoplasm, cytoskeleton. Note=Innermost portion of the desmosomal plaque. Colocalizes with epidermal KRT5-KRT14 and simple KRT8-KRT18 keratins and VIM intermediate filaments network. TISSUE SPECIFICITY: Isoform DPI is apparently an obligate constituent of all desmosomes. Isoform DPII resides predominantly in tissues and cells of stratified origin. 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. DOMAIN: The N-terminal region is required for localization to the desmosomal plaque and interacts with the N-terminal region of plakophilin 1. DOMAIN: The three tandem plakin repeat regions in the C-terminus mediate binding to intermediate filaments. 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. PTM: Substrate of transglutaminase. Some glutamines and lysines are cross-linked to other desmoplakin molecules, to other proteins such as keratin, envoplakin, periplakin and involucrin, and to lipids like omega-hydroxyceramide. DISEASE: Defects in DSP are the cause of palmoplantar keratoderma striate type 2 (SPPK2) [MIM:612908]; also known as keratosis palmoplantaris striata II. SPPK2 is characterized by skin thickening in 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. DISEASE: Defects in DSP are the cause of cardiomyopathy dilated with woolly hair and keratoderma (DCWHK) [MIM:605676]; also known as Carvajal syndrome or palmoplantar keratoderma with left ventricular cardiomyopathy and woolly hair. DCWHK is an autosomal recessive cardiocutaneous syndrome characterized by a generalized striate keratoderma particularly affecting the palmoplantar epidermis, woolly hair, and dilated left ventricular cardiomyopathy. DISEASE: Defects in DSP are the cause of familial arrhythmogenic right ventricular dysplasia type 8 (ARVD8) [MIM:607450]; also known as arrhythmogenic right ventricular cardiomyopathy 8 (ARVC8). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall. DISEASE: Defects in DSP are the cause of skin fragility-woolly hair syndrome (SFWHS) [MIM:607655]. SFWHS is an autosomal recessive genodermatosis characterized by focal and diffuse palmoplantar keratoderma, hyperkeratotic plaques on the trunk and limbs, and woolly hair with varying degrees of alopecia. DISEASE: Defects in DSP are the cause of epidermolysis bullosa lethal acantholytic (EBLA) [MIM:609638]. EBLA is 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. SIMILARITY: Belongs to the plakin or cytolinker family. SIMILARITY: Contains 17 plectin repeats. SIMILARITY: Contains 1 SH3 domain. SIMILARITY: Contains 6 spectrin repeats. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/DSP"; WEB RESOURCE: Name=Wikipedia; Note=Desmoplakin entry; URL="http://en.wikipedia.org/wiki/Desmoplakin";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P15924
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0003723 RNA binding GO:0005080 protein kinase C binding GO:0005198 structural molecule activity GO:0005200 structural constituent of cytoskeleton GO:0005515 protein binding GO:0030674 protein binding, bridging GO:0050839 cell adhesion molecule binding GO:0086083 cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication GO:0097110 scaffold protein binding
Biological Process: GO:0002934 desmosome organization GO:0003223 ventricular compact myocardium morphogenesis GO:0008544 epidermis development GO:0018149 peptide cross-linking GO:0030216 keratinocyte differentiation GO:0031424 keratinization GO:0034332 adherens junction organization GO:0042060 wound healing GO:0043312 neutrophil degranulation GO:0043588 skin development GO:0045104 intermediate filament cytoskeleton organization GO:0045109 intermediate filament organization GO:0070268 cornification GO:0071896 protein localization to adherens junction GO:0086073 bundle of His cell-Purkinje myocyte adhesion involved in cell communication GO:0086091 regulation of heart rate by cardiac conduction GO:0098609 cell-cell adhesion GO:0098911 regulation of ventricular cardiac muscle cell action potential
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
