P15924

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. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=DPI; Synonyms=DP1; IsoId=P15924-1; Sequence=Displayed; Name=DPII; Synonyms=DP2; IsoId=P15924-2; Sequence=VSP_005070; 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"; GENE SYNONYMS:DSP. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 2871 AA; 331774 MW; 5770CC6B4F9F9F7B CRC64;

DESP_HUMAN

urn:biopax:ModificationFeature:DESP_HUMAN_1, urn:biopax:ModificationFeature:DESP_HUMAN_10, urn:biopax:ModificationFeature:DESP_HUMAN_11, urn:biopax:ModificationFeature:DESP_HUMAN_12, urn:biopax:ModificationFeature:DESP_HUMAN_13, urn:biopax:ModificationFeature:DESP_HUMAN_14, urn:biopax:ModificationFeature:DESP_HUMAN_15, urn:biopax:ModificationFeature:DESP_HUMAN_16, urn:biopax:ModificationFeature:DESP_HUMAN_17, urn:biopax:ModificationFeature:DESP_HUMAN_18, urn:biopax:ModificationFeature:DESP_HUMAN_19, urn:biopax:ModificationFeature:DESP_HUMAN_2, urn:biopax:ModificationFeature:DESP_HUMAN_20, urn:biopax:ModificationFeature:DESP_HUMAN_21, urn:biopax:ModificationFeature:DESP_HUMAN_3, urn:biopax:ModificationFeature:DESP_HUMAN_4, urn:biopax:ModificationFeature:DESP_HUMAN_5, urn:biopax:ModificationFeature:DESP_HUMAN_6, urn:biopax:ModificationFeature:DESP_HUMAN_7, urn:biopax:ModificationFeature:DESP_HUMAN_8, urn:biopax:ModificationFeature:DESP_HUMAN_9

MSCNGGSHPRINTLGRMIRAESGPDLRYEVTSGGGGTSRMYYSRRGVITDQNSDGYCQTGTMSRHQNQNTIQELLQNCSDCLMRAELIVQPELKYGDGIQLTRSRELDECFAQANDQMEILDSLIREMRQMGQPCDAYQKRLLQLQEQMRALYKAISVPRVRRASSKGGGGYTCQSGSGWDEFTKHVTSECLGWMRQQRAEMDMVAWGVDLASVEQHINSHRGIHNSIGDYRWQLDKIKADLREKSAIYQLEEEYENLLKASFERMDHLRQLQNIIQATSREIMWINDCEEEELLYDWSDKNTNIAQKQEAFSIRMSQLEVKEKELNKLKQESDQLVLNQHPASDKIEAYMDTLQTQWSWILQITKCIDVHLKENAAYFQFFEEAQSTEAYLKGLQDSIRKKYPCDKNMPLQHLLEQIKELEKEREKILEYKRQVQNLVNKSKKIVQLKPRNPDYRSNKPIILRALCDYKQDQKIVHKGDECILKDNNERSKWYVTGPGGVDMLVPSVGLIIPPPNPLAVDLSCKIEQYYEAILALWNQLYINMKSLVSWHYCMIDIEKIRAMTIAKLKTMRQEDYMKTIADLELHYQEFIRNSQGSEMFGDDDKRKIQSQFTDAQKHYQTLVIQLPGYPQHQTVTTTEITHHGTCQDVNHNKVIETNRENDKQETWMLMELQKIRRQIEHCEGRMTLKNLPLADQGSSHHITVKINELKSVQNDSQAIAEVLNQLKDMLANFRGSEKYCYLQNEVFGLFQKLENINGVTDGYLNSLCTVRALLQAILQTEDMLKVYEARLTEEETVCLDLDKVEAYRCGLKKIKNDLNLKKSLLATMKTELQKAQQIHSQTSQQYPLYDLDLGKFGEKVTQLTDRWQRIDKQIDFRLWDLEKQIKQLRNYRDNYQAFCKWLYDAKRRQDSLESMKFGDSNTVMRFLNEQKNLHSEISGKRDKSEEVQKIAELCANSIKDYELQLASYTSGLETLLNIPIKRTMIQSPSGVILQEAADVHARYIELLTRSGDYYRFLSEMLKSLEDLKLKNTKIEVLEEELRLARDANSENCNKNKFLDQNLQKYQAECSQFKAKLASLEELKRQAELDGKSAKQNLDKCYGQIKELNEKITRLTYEIEDEKRRRKSVEDRFDQQKNDYDQLQKARQCEKENLGWQKLESEKAIKEKEYEIERLRVLLQEEGTRKREYENELAKVRNHYNEEMSNLRNKYETEINITKTTIKEISMQKEDDSKNLRNQLDRLSRENRDLKDEIVRLNDSILQATEQRRRAEENALQQKACGSEIMQKKQHLEIELKQVMQQRSEDNARHKQSLEEAAKTIQDKNKEIERLKAEFQEEAKRRWEYENELSKVRNNYDEEIISLKNQFETEINITKTTIHQLTMQKEEDTSGYRAQIDNLTRENRSLSEEIKRLKNTLTQTTENLRRVEEDIQQQKATGSEVSQRKQQLEVELRQVTQMRTEESVRYKQSLDDAAKTIQDKNKEIERLKQLIDKETNDRKCLEDENARLQRVQYDLQKANSSATETINKLKVQEQELTRLRIDYERVSQERTVKDQDITRFQNSLKELQLQKQKVEEELNRLKRTASEDSCKRKKLEEELEGMRRSLKEQAIKITNLTQQLEQASIVKKRSEDDLRQQRDVLDGHLREKQRTQEELRRLSSEVEALRRQLLQEQESVKQAHLRNEHFQKAIEDKSRSLNESKIEIERLQSLTENLTKEHLMLEEELRNLRLEYDDLRRGRSEADSDKNATILELRSQLQISNNRTLELQGLINDLQRERENLRQEIEKFQKQALEASNRIQESKNQCTQVVQERESLLVKIKVLEQDKARLQRLEDELNRAKSTLEAETRVKQRLECEKQQIQNDLNQWKTQYSRKEEAIRKIESEREKSEREKNSLRSEIERLQAEIKRIEERCRRKLEDSTRETQSQLETERSRYQREIDKLRQRPYGSHRETQTECEWTVDTSKLVFDGLRKKVTAMQLYECQLIDKTTLDKLLKGKKSVEEVASEIQPFLRGAGSIAGASASPKEKYSLVEAKRKKLISPESTVMLLEAQAATGGIIDPHRNEKLTVDSAIARDLIDFDDRQQIYAAEKAITGFDDPFSGKTVSVSEAIKKNLIDRETGMRLLEAQIASGGVVDPVNSVFLPKDVALARGLIDRDLYRSLNDPRDSQKNFVDPVTKKKVSYVQLKERCRIEPHTGLLLLSVQKRSMSFQGIRQPVTVTELVDSGILRPSTVNELESGQISYDEVGERIKDFLQGSSCIAGIYNETTKQKLGIYEAMKIGLVRPGTALELLEAQAATGFIVDPVSNLRLPVEEAYKRGLVGIEFKEKLLSAERAVTGYNDPETGNIISLFQAMNKELIEKGHGIRLLEAQIATGGIIDPKESHRLPVDIAYKRGYFNEELSEILSDPSDDTKGFFDPNTEENLTYLQLKERCIKDEETGLCLLPLKEKKKQVQTSQKNTLRKRRVVIVDPETNKEMSVQEAYKKGLIDYETFKELCEQECEWEEITITGSDGSTRVVLVDRKTGSQYDIQDAIDKGLVDRKFFDQYRSGSLSLTQFADMISLKNGVGTSSSMGSGVSDDVFSSSRHESVSKISTISSVRNLTIRSSSFSDTLEESSPIAAIFDTENLEKISITEGIERGIVDSITGQRLLEAQACTGGIIHPTTGQKLSLQDAVSQGVIDQDMATRLKPAQKAFIGFEGVKGKKKMSAAEAVKEKWLPYEAGQRFLEFQYLTGGLVDPEVHGRISTEEAIRKGFIDGRAAQRLQDTSSYAKILTCPKTKLKISYKDAINRSMVEDITGLRLLEAASVSSKGLPSPYNMSSAPGSRSGSRSGSRSGSRSGSRSGSRRGSFDATGNSSYSYSYSFSSSSIGH