MGP Database

MGP000881

UniProt Annotations

Entry Information

Gene Name	desmoplakin
Protein Entry	DESP_HUMAN
UniProt ID	P15924
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=3; Name=DPI; Synonyms=DP1; IsoId=P15924-1; Sequence=Displayed; Name=DPII; Synonyms=DP2; IsoId=P15924-2; Sequence=VSP_005070; Name=DSPIa; IsoId=P15924-3; Sequence=VSP_053769; Note=Minor isoform.;
Disease	Arrhythmogenic right ventricular dysplasia, familial, 8 (ARVD8) [MIM:607450]: 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. {ECO:0000269\|PubMed:12373648, ECO:0000269\|PubMed:15941723, ECO:0000269\|PubMed:20031617}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Cardiomyopathy, dilated, with woolly hair and keratoderma (DCWHK) [MIM:605676]: An autosomal recessive cardiocutaneous syndrome characterized by a generalized striate keratoderma particularly affecting the palmoplantar epidermis, woolly hair, and dilated left ventricular cardiomyopathy. {ECO:0000269\|PubMed:11063735}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Cardiomyopathy, dilated, with woolly hair, keratoderma, and tooth agenesis (DCWHKTA) [MIM:615821]: A cardiocutaneous syndrome characterized by biventricular dilated cardiomyopathy, hyperkeratosis, woolly hair, palmoplantar keratoderma, and hypo/oligodontia. {ECO:0000269\|PubMed:16628197, ECO:0000269\|PubMed:20940358, ECO:0000269\|PubMed:22795705}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Epidermolysis bullosa, lethal acantholytic (EBLA) [MIM:609638]: 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. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Keratoderma, palmoplantar, striate 2 (SPPK2) [MIM:612908]: 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. {ECO:0000269\|PubMed:9887343}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Skin fragility-woolly hair syndrome (SFWHS) [MIM:607655]: 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. {ECO:0000269\|PubMed:11841538}. Note=The disease is caused by mutations affecting the gene represented in this entry.
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.
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.
Interaction	Q13835-2:PKP1; NbExp=2; IntAct=EBI-355041, EBI-9087684;
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. {ECO:0000269\|PubMed:18220336, ECO:0000269\|PubMed:18669648, ECO:0000269\|PubMed:20068231, ECO:0000269\|PubMed:21406692}.
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 (PubMed:9651377). {ECO:0000269\|PubMed:9651377}.
Similarity	Belongs to the plakin or cytolinker family. {ECO:0000305}.
Similarity	Contains 17 plectin repeats. {ECO:0000305}.
Similarity	Contains 1 SH3 domain. {ECO:0000305}.
Similarity	Contains 6 spectrin repeats. {ECO:0000305}.
Subcellular Location	Cell junction, desmosome {ECO:0000269\|PubMed:12802069}. Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:12802069}. Note=Innermost portion of the desmosomal plaque. Colocalizes with epidermal KRT5-KRT14 and simple KRT8-KRT18 keratins and VIM intermediate filaments network.
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. Interacts with PKP2. {ECO:0000269\|PubMed:12482924, ECO:0000269\|PubMed:21062920, ECO:0000269\|PubMed:22781308}.
Tissue Specificity	Isoform DPI is apparently an obligate constituent of all desmosomes. Isoform DPII resides predominantly in tissues and cells of stratified origin.
Web Resource	Name=Wikipedia; Note=Desmoplakin entry; URL="http://en.wikipedia.org/wiki/Desmoplakin";