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P15924 (DESP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 181. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Desmoplakin

Short name=DP
Alternative name(s):
250/210 kDa paraneoplastic pemphigus antigen
Gene names
Name:DSP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length2871 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 structure

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. Ref.13 Ref.23 Ref.25

Subcellular location

Cell junctiondesmosome. Cytoplasmcytoskeleton. Note: Innermost portion of the desmosomal plaque. Colocalizes with epidermal KRT5-KRT14 and simple KRT8-KRT18 keratins and VIM intermediate filaments network. Ref.14

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. Ref.26 Ref.27

The N-terminal region is required for localization to the desmosomal plaque and interacts with the N-terminal region of plakophilin 1. Ref.26 Ref.27

The three tandem plakin repeat regions in the C-terminus mediate binding to intermediate filaments. Ref.26 Ref.27

Post-translational modification

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.

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 (Ref.9).

Involvement in 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.28 Ref.32 Ref.33

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.29

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.

Sequence similarities

Belongs to the plakin or cytolinker family.

Contains 17 plectin repeats.

Contains 1 SH3 domain.

Contains 6 spectrin repeats.

Ontologies

Keywords
   Cellular componentCell junction
Cytoplasm
Cytoskeleton
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseCardiomyopathy
Disease mutation
Epidermolysis bullosa
Palmoplantar keratoderma
   DomainCoiled coil
Repeat
   PTMLipoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadherens junction organization

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Traceable author statement. Source: Reactome

bundle of His cell to Purkinje myocyte communication

Inferred from mutant phenotype Ref.25. Source: BHF-UCL

cellular component disassembly involved in execution phase of apoptosis

Traceable author statement. Source: Reactome

desmosome organization

Inferred from sequence or structural similarity PubMed 16917092. Source: BHF-UCL

epidermis development

Traceable author statement Ref.10. Source: ProtInc

intermediate filament organization

Inferred from sequence or structural similarity PubMed 16917092. Source: BHF-UCL

keratinocyte differentiation

Inferred from direct assay PubMed 10908733. Source: UniProtKB

peptide cross-linking

Inferred from direct assay PubMed 10908733. Source: UniProtKB

protein localization to adherens junction

Inferred from sequence or structural similarity PubMed 16917092. Source: BHF-UCL

regulation of heart rate by cardiac conduction

Inferred from mutant phenotype Ref.25. Source: BHF-UCL

single organismal cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

ventricular cardiac muscle cell action potential

Inferred from mutant phenotype Ref.25. Source: BHF-UCL

ventricular compact myocardium morphogenesis

Inferred from sequence or structural similarity PubMed 16917092. Source: BHF-UCL

wound healing

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentbasolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

cornified envelope

Inferred from direct assay PubMed 10908733. Source: UniProtKB

desmosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 19199708PubMed 20458337PubMed 23376485. Source: UniProt

fascia adherens

Inferred from electronic annotation. Source: Ensembl

intercalated disc

Inferred from direct assay PubMed 22889254. Source: BHF-UCL

intermediate filament

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 21630459. Source: UniProt

plasma membrane

Inferred from direct assay PubMed 16917092. Source: BHF-UCL

   Molecular_functionpoly(A) RNA binding

Inferred from direct assay PubMed 22658674. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.13. Source: UniProtKB

protein binding, bridging

Inferred from direct assay PubMed 10908733. Source: UniProtKB

protein kinase C binding

Inferred from physical interaction PubMed 18474624. Source: BHF-UCL

scaffold protein binding

Inferred from physical interaction PubMed 10852826. Source: BHF-UCL

structural constituent of cytoskeleton

Traceable author statement Ref.10. Source: ProtInc

structural molecule activity

Inferred from direct assay PubMed 10908733. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PKP1Q13835-22EBI-355041,EBI-9087684

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform DPI (identifier: P15924-1)

Also known as: DP1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform DPII (identifier: P15924-2)

Also known as: DP2;

The sequence of this isoform differs from the canonical sequence as follows:
     1195-1793: Missing.
Isoform DSPIa (identifier: P15924-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1351-1793: Missing.
Note: Minor isoform.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 28712871Desmoplakin
PRO_0000078144

Regions

Repeat178 – 27194Spectrin 1
Repeat272 – 375104Spectrin 2
Repeat376 – 44671Spectrin 3a
Domain447 – 51569SH3
Repeat516 – 54530Spectrin 3b
Repeat546 – 62782Spectrin 4
Repeat654 – 769116Spectrin 5
Repeat770 – 883114Spectrin 6
Repeat2009 – 204537Plectin 1
Repeat2046 – 208338Plectin 2
Repeat2084 – 212138Plectin 3
Repeat2122 – 215938Plectin 4
Repeat2163 – 219735Plectin 5
Repeat2198 – 223336Plectin 6
Repeat2251 – 228838Plectin 7
Repeat2289 – 232638Plectin 8
Repeat2327 – 236438Plectin 9
Repeat2365 – 240238Plectin 10
Repeat2406 – 244035Plectin 11
Repeat2456 – 249338Plectin 12
Repeat2507 – 254438Plectin 13
Repeat2610 – 264738Plectin 14
Repeat2648 – 268538Plectin 15
Repeat2724 – 276138Plectin 16
Repeat2762 – 279938Plectin 17
Region1 – 10561056Globular 1
Region1 – 584584Interacts with plakophilin 1 and junction plakoglobin
Region1057 – 1945889Central fibrous rod domain
Region1946 – 2871926Globular 2
Region1960 – 22082494.5 X 38 AA tandem repeats (Domain A)
Region2244 – 24462034.5 X 38 AA tandem repeats (Domain B)
Region2609 – 28222144.5 X 38 AA tandem repeats (Domain C)
Region2824 – 2847246 X 4 AA tandem repeats of G-S-R-[SR]
Coiled coil1018 – 1945928 Potential

Amino acid modifications

Modified residue221Phosphoserine Ref.24
Modified residue1651Phosphoserine Ref.17
Modified residue1661Phosphoserine Ref.17
Modified residue1761Phosphoserine Ref.17
Modified residue20241Phosphoserine Ref.17 Ref.21
Modified residue22071Phosphoserine Ref.21
Modified residue22091Phosphoserine Ref.17 Ref.21 Ref.24
Modified residue28151Phosphoserine Ref.17 Ref.21
Modified residue28201Phosphoserine Ref.24
Modified residue28211Phosphoserine Ref.17
Modified residue28251Phosphoserine Ref.15 Ref.17 Ref.21 Ref.24
Modified residue28491Phosphoserine Ref.17
Modified residue28531Phosphothreonine Ref.17
Modified residue28681Phosphoserine Ref.17
Lipidation24801Omega-hydroxyceramide glutamate ester Potential

Natural variations

Alternative sequence1195 – 1793599Missing in isoform DPII.
VSP_005070
Alternative sequence1351 – 1793443Missing in isoform DSPIa.
VSP_053769
Natural variant2871N → K in SFWHS. Ref.29
VAR_015569
Natural variant2991S → R in ARVD8. Ref.28 Ref.32 Ref.33
Corresponds to variant rs121912992 [ dbSNP | Ensembl ].
VAR_015402
Natural variant3051I → F. Ref.33 Ref.34
Corresponds to variant rs17604693 [ dbSNP | Ensembl ].
VAR_033862
Natural variant4451I → V in ARVD8.
VAR_065693
Natural variant12551R → K in ARVD8. Ref.32 Ref.33
VAR_023814
Natural variant15051A → V. Ref.33
VAR_065694
Natural variant15121Y → C. Ref.33 Ref.34
Corresponds to variant rs2076299 [ dbSNP | Ensembl ].
VAR_020468
Natural variant15261N → K. Ref.33 Ref.34
Corresponds to variant rs28763966 [ dbSNP | Ensembl ].
VAR_065695
Natural variant15371R → C. Ref.33 Ref.34
Corresponds to variant rs28763967 [ dbSNP | Ensembl ].
VAR_065696
Natural variant17381R → Q. Ref.33 Ref.34
Corresponds to variant rs6929069 [ dbSNP | Ensembl ].
VAR_023815
Natural variant17751R → I in ARVD8. Ref.32 Ref.33
Corresponds to variant rs34738426 [ dbSNP | Ensembl ].
VAR_023816
Natural variant18331E → V. Ref.23 Ref.34
Corresponds to variant rs78652302 [ dbSNP | Ensembl ].
VAR_065697
Natural variant23661R → C in SFWHS. Ref.29
Corresponds to variant rs28931610 [ dbSNP | Ensembl ].
VAR_015570
Natural variant23751G → R in a case of recessive arrhythmogenic right ventricular cardiomyopathy with skin abnormalities and woolly hair. Ref.30
VAR_018158

Experimental info

Mutagenesis28491S → G: Increases association with KRT5-KRT14, KRT8-KRT18 or VIM intermediate filaments. Ref.14
Sequence conflict9051A → R in AAA85135. Ref.1
Sequence conflict11201D → R in AAA35766. Ref.5
Sequence conflict2687 – 26882RL → SV in AAA85135. Ref.1
Sequence conflict2687 – 26882RL → SV in AAA35766. Ref.5

Secondary structure

................................................................................................................................. 2871
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform DPI (DP1) [UniParc].

Last modified October 3, 2006. Version 3.
Checksum: 5770CC6B4F9F9F7B

FASTA2,871331,774
        10         20         30         40         50         60 
MSCNGGSHPR INTLGRMIRA ESGPDLRYEV TSGGGGTSRM YYSRRGVITD QNSDGYCQTG 

        70         80         90        100        110        120 
TMSRHQNQNT IQELLQNCSD CLMRAELIVQ PELKYGDGIQ LTRSRELDEC FAQANDQMEI 

       130        140        150        160        170        180 
LDSLIREMRQ MGQPCDAYQK RLLQLQEQMR ALYKAISVPR VRRASSKGGG GYTCQSGSGW 

       190        200        210        220        230        240 
DEFTKHVTSE CLGWMRQQRA EMDMVAWGVD LASVEQHINS HRGIHNSIGD YRWQLDKIKA 

       250        260        270        280        290        300 
DLREKSAIYQ LEEEYENLLK ASFERMDHLR QLQNIIQATS REIMWINDCE EEELLYDWSD 

       310        320        330        340        350        360 
KNTNIAQKQE AFSIRMSQLE VKEKELNKLK QESDQLVLNQ HPASDKIEAY MDTLQTQWSW 

       370        380        390        400        410        420 
ILQITKCIDV HLKENAAYFQ FFEEAQSTEA YLKGLQDSIR KKYPCDKNMP LQHLLEQIKE 

       430        440        450        460        470        480 
LEKEREKILE YKRQVQNLVN KSKKIVQLKP RNPDYRSNKP IILRALCDYK QDQKIVHKGD 

       490        500        510        520        530        540 
ECILKDNNER SKWYVTGPGG VDMLVPSVGL IIPPPNPLAV DLSCKIEQYY EAILALWNQL 

       550        560        570        580        590        600 
YINMKSLVSW HYCMIDIEKI RAMTIAKLKT MRQEDYMKTI ADLELHYQEF IRNSQGSEMF 

       610        620        630        640        650        660 
GDDDKRKIQS QFTDAQKHYQ TLVIQLPGYP QHQTVTTTEI THHGTCQDVN HNKVIETNRE 

       670        680        690        700        710        720 
NDKQETWMLM ELQKIRRQIE HCEGRMTLKN LPLADQGSSH HITVKINELK SVQNDSQAIA 

       730        740        750        760        770        780 
EVLNQLKDML ANFRGSEKYC YLQNEVFGLF QKLENINGVT DGYLNSLCTV RALLQAILQT 

       790        800        810        820        830        840 
EDMLKVYEAR LTEEETVCLD LDKVEAYRCG LKKIKNDLNL KKSLLATMKT ELQKAQQIHS 

       850        860        870        880        890        900 
QTSQQYPLYD LDLGKFGEKV TQLTDRWQRI DKQIDFRLWD LEKQIKQLRN YRDNYQAFCK 

       910        920        930        940        950        960 
WLYDAKRRQD SLESMKFGDS NTVMRFLNEQ KNLHSEISGK RDKSEEVQKI AELCANSIKD 

       970        980        990       1000       1010       1020 
YELQLASYTS GLETLLNIPI KRTMIQSPSG VILQEAADVH ARYIELLTRS GDYYRFLSEM 

      1030       1040       1050       1060       1070       1080 
LKSLEDLKLK NTKIEVLEEE LRLARDANSE NCNKNKFLDQ NLQKYQAECS QFKAKLASLE 

      1090       1100       1110       1120       1130       1140 
ELKRQAELDG KSAKQNLDKC YGQIKELNEK ITRLTYEIED EKRRRKSVED RFDQQKNDYD 

      1150       1160       1170       1180       1190       1200 
QLQKARQCEK ENLGWQKLES EKAIKEKEYE IERLRVLLQE EGTRKREYEN ELAKVRNHYN 

      1210       1220       1230       1240       1250       1260 
EEMSNLRNKY ETEINITKTT IKEISMQKED DSKNLRNQLD RLSRENRDLK DEIVRLNDSI 

      1270       1280       1290       1300       1310       1320 
LQATEQRRRA EENALQQKAC GSEIMQKKQH LEIELKQVMQ QRSEDNARHK QSLEEAAKTI 

      1330       1340       1350       1360       1370       1380 
QDKNKEIERL KAEFQEEAKR RWEYENELSK VRNNYDEEII SLKNQFETEI NITKTTIHQL 

      1390       1400       1410       1420       1430       1440 
TMQKEEDTSG YRAQIDNLTR ENRSLSEEIK RLKNTLTQTT ENLRRVEEDI QQQKATGSEV 

      1450       1460       1470       1480       1490       1500 
SQRKQQLEVE LRQVTQMRTE ESVRYKQSLD DAAKTIQDKN KEIERLKQLI DKETNDRKCL 

      1510       1520       1530       1540       1550       1560 
EDENARLQRV QYDLQKANSS ATETINKLKV QEQELTRLRI DYERVSQERT VKDQDITRFQ 

      1570       1580       1590       1600       1610       1620 
NSLKELQLQK QKVEEELNRL KRTASEDSCK RKKLEEELEG MRRSLKEQAI KITNLTQQLE 

      1630       1640       1650       1660       1670       1680 
QASIVKKRSE DDLRQQRDVL DGHLREKQRT QEELRRLSSE VEALRRQLLQ EQESVKQAHL 

      1690       1700       1710       1720       1730       1740 
RNEHFQKAIE DKSRSLNESK IEIERLQSLT ENLTKEHLML EEELRNLRLE YDDLRRGRSE 

      1750       1760       1770       1780       1790       1800 
ADSDKNATIL ELRSQLQISN NRTLELQGLI NDLQRERENL RQEIEKFQKQ ALEASNRIQE 

      1810       1820       1830       1840       1850       1860 
SKNQCTQVVQ ERESLLVKIK VLEQDKARLQ RLEDELNRAK STLEAETRVK QRLECEKQQI 

      1870       1880       1890       1900       1910       1920 
QNDLNQWKTQ YSRKEEAIRK IESEREKSER EKNSLRSEIE RLQAEIKRIE ERCRRKLEDS 

      1930       1940       1950       1960       1970       1980 
TRETQSQLET ERSRYQREID KLRQRPYGSH RETQTECEWT VDTSKLVFDG LRKKVTAMQL 

      1990       2000       2010       2020       2030       2040 
YECQLIDKTT LDKLLKGKKS VEEVASEIQP FLRGAGSIAG ASASPKEKYS LVEAKRKKLI 

      2050       2060       2070       2080       2090       2100 
SPESTVMLLE AQAATGGIID PHRNEKLTVD SAIARDLIDF DDRQQIYAAE KAITGFDDPF 

      2110       2120       2130       2140       2150       2160 
SGKTVSVSEA IKKNLIDRET GMRLLEAQIA SGGVVDPVNS VFLPKDVALA RGLIDRDLYR 

      2170       2180       2190       2200       2210       2220 
SLNDPRDSQK NFVDPVTKKK VSYVQLKERC RIEPHTGLLL LSVQKRSMSF QGIRQPVTVT 

      2230       2240       2250       2260       2270       2280 
ELVDSGILRP STVNELESGQ ISYDEVGERI KDFLQGSSCI AGIYNETTKQ KLGIYEAMKI 

      2290       2300       2310       2320       2330       2340 
GLVRPGTALE LLEAQAATGF IVDPVSNLRL PVEEAYKRGL VGIEFKEKLL SAERAVTGYN 

      2350       2360       2370       2380       2390       2400 
DPETGNIISL FQAMNKELIE KGHGIRLLEA QIATGGIIDP KESHRLPVDI AYKRGYFNEE 

      2410       2420       2430       2440       2450       2460 
LSEILSDPSD DTKGFFDPNT EENLTYLQLK ERCIKDEETG LCLLPLKEKK KQVQTSQKNT 

      2470       2480       2490       2500       2510       2520 
LRKRRVVIVD PETNKEMSVQ EAYKKGLIDY ETFKELCEQE CEWEEITITG SDGSTRVVLV 

      2530       2540       2550       2560       2570       2580 
DRKTGSQYDI QDAIDKGLVD RKFFDQYRSG SLSLTQFADM ISLKNGVGTS SSMGSGVSDD 

      2590       2600       2610       2620       2630       2640 
VFSSSRHESV SKISTISSVR NLTIRSSSFS DTLEESSPIA AIFDTENLEK ISITEGIERG 

      2650       2660       2670       2680       2690       2700 
IVDSITGQRL LEAQACTGGI IHPTTGQKLS LQDAVSQGVI DQDMATRLKP AQKAFIGFEG 

      2710       2720       2730       2740       2750       2760 
VKGKKKMSAA EAVKEKWLPY EAGQRFLEFQ YLTGGLVDPE VHGRISTEEA IRKGFIDGRA 

      2770       2780       2790       2800       2810       2820 
AQRLQDTSSY AKILTCPKTK LKISYKDAIN RSMVEDITGL RLLEAASVSS KGLPSPYNMS 

      2830       2840       2850       2860       2870 
SAPGSRSGSR SGSRSGSRSG SRSGSRRGSF DATGNSSYSY SYSFSSSSIG H 

« Hide

Isoform DPII (DP2) [UniParc].

Checksum: 84F0CD39B48E1339
Show »

FASTA2,272260,119
Isoform DSPIa [UniParc].

Checksum: B26951DA08A0620C
Show »

FASTA2,428278,916

References

« Hide 'large scale' references
[1]"Molecular structure of the human desmoplakin I and II amino terminus."
Virata M.L.A., Wagner R.M., Parry D.A.D., Green K.J.
Proc. Natl. Acad. Sci. U.S.A. 89:544-548(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DPI).
Tissue: Foreskin.
[2]"Identification and characterization of DSPIa, a novel isoform of human desmoplakin."
Cabral R.M., Wan H., Cole C.L., Abrams D.J., Kelsell D.P., South A.P.
Cell Tissue Res. 341:121-129(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DSPIA).
[3]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DPII).
[5]"Structure of the human desmoplakins. Implications for function in the desmosomal plaque."
Green K.J., Parry D.A.D., Steinert P.M., Virata M.L.A., Wagner R.M., Angst B.D., Nilles L.A.
J. Biol. Chem. 265:2603-2612(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1120-2871 (ISOFORM DPI).
Tissue: Foreskin.
[6]Erratum
Green K.J., Parry D.A.D., Steinert P.M., Virata M.L.A., Wagner R.M., Angst B.D., Nilles L.A.
J. Biol. Chem. 265:11406-11407(1990) [PubMed] [Europe PMC] [Abstract]
[7]"Striate palmoplantar keratoderma resulting from desmoplakin haploinsufficiency."
Whittock N.V., Ashton G.H., Dopping-Hepenstal P.J., Gratian M.J., Keane F.M., Eady R.A.J., McGrath J.A.
J. Invest. Dermatol. 113:940-946(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2854-2871.
Tissue: Skin.
[8]"The amino-terminal domain of desmoplakin binds to plakoglobin and clusters desmosomal cadherin-plakoglobin complexes."
Kowalczyk A.P., Bornslaeger E.A., Borgwardt J.E., Palka H.L., Dhaliwal A.S., Corcoran C.M., Denning M.F., Green K.J.
J. Cell Biol. 139:773-784(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[9]"Ceramides are bound to structural proteins of the human foreskin epidermal cornified cell envelope."
Marekov L.N., Steinert P.M.
J. Biol. Chem. 273:17763-17770(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: LIPIDATION.
[10]"Haploinsufficiency of desmoplakin causes a striate subtype of palmoplantar keratoderma."
Armstrong D.K., McKenna K.E., Purkis P.E., Green K.J., Eady R.A.J., Leigh I.M., Hughes A.E.
Hum. Mol. Genet. 8:143-148(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SPPK2.
[11]Erratum
Armstrong D.K., McKenna K.E., Purkis P.E., Green K.J., Eady R.A.J., Leigh I.M., Hughes A.E.
Hum. Mol. Genet. 8:943-943(1999)
[12]"Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma."
Norgett E.E., Hatsell S.J., Carvajal-Huerta L., Cabezas J.-C.R., Common J., Purkis P.E., Whittock N.V., Leigh I.M., Stevens H.P., Kelsell D.P.
Hum. Mol. Genet. 9:2761-2766(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN DCWHK.
[13]"Analysis of the interactions between BP180, BP230, plectin and the integrin alpha6beta4 important for hemidesmosome assembly."
Koster J., Geerts D., Favre B., Borradori L., Sonnenberg A.
J. Cell Sci. 116:387-399(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH COL17A1.
[14]"Interaction of the bullous pemphigoid antigen 1 (BP230) and desmoplakin with intermediate filaments is mediated by distinct sequences within their COOH terminus."
Fontao L., Favre B., Riou S., Geerts D., Jaunin F., Saurat J.H., Green K.J., Sonnenberg A., Borradori L.
Mol. Biol. Cell 14:1978-1992(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH KERATIN FILAMENTS, MUTAGENESIS OF SER-2849, SUBCELLULAR LOCATION.
[15]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2825, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[17]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165; SER-166; SER-176; SER-2024; SER-2209; SER-2815; SER-2821; SER-2825; SER-2849; THR-2853 AND SER-2868, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[18]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[21]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2024; SER-2207; SER-2209; SER-2815 AND SER-2825, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"Mechanistic insights into arrhythmogenic right ventricular cardiomyopathy caused by desmocollin-2 mutations."
Gehmlich K., Syrris P., Peskett E., Evans A., Ehler E., Asimaki A., Anastasakis A., Tsatsopoulou A., Vouliotis A.I., Stefanadis C., Saffitz J.E., Protonotarios N., McKenna W.J.
Cardiovasc. Res. 90:77-87(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DSC2, VARIANT VAL-1833.
[24]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22; SER-2209; SER-2820 AND SER-2825, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]"Molecular insights into arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 missense mutations."
Kirchner F., Schuetz A., Boldt L.H., Martens K., Dittmar G., Haverkamp W., Thierfelder L., Heinemann U., Gerull B.
Circ. Cardiovasc. Genet. 5:400-411(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PKP2.
[26]"Structures of two intermediate filament-binding fragments of desmoplakin reveal a unique repeat motif structure."
Choi H.J., Park-Snyder S., Pascoe L.T., Green K.J., Weis W.I.
Nat. Struct. Biol. 9:612-620(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 2209-2456, X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 2609-2822, DOMAIN PLAKIN REPEATS.
[27]"Crystal structure of a rigid four-spectrin-repeat fragment of the human desmoplakin plakin domain."
Choi H.J., Weis W.I.
J. Mol. Biol. 409:800-812(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 178-627, DOMAIN SPECTRIN REPEATS, DOMAIN SH3.
[28]"Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy."
Rampazzo A., Nava A., Malacrida S., Beffagna G., Bauce B., Rossi V., Zimbello R., Simionati B., Basso C., Thiene G., Towbin J.A., Danieli G.A.
Am. J. Hum. Genet. 71:1200-1206(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARVD8 ARG-299.
[29]"Compound heterozygosity for non-sense and mis-sense mutations in desmoplakin underlies skin fragility/woolly hair syndrome."
Whittock N.V., Wan H., Morley S.M., Garzon M.C., Kristal L., Hyde P., McLean W.H.I., Pulkkinen L., Uitto J., Christiano A.M., Eady R.A.J., McGrath J.A.
J. Invest. Dermatol. 118:232-238(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SFWHS LYS-287 AND CYS-2366.
[30]"A recessive mutation in desmoplakin causes arrhythmogenic right ventricular dysplasia, skin disorder, and woolly hair."
Alcalai R., Metzger S., Rosenheck S., Meiner V., Chajek-Shaul T.
J. Am. Coll. Cardiol. 42:319-327(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARRHYTHMOGENIC CARDIOMYOPATHY ARG-2375.
[31]"Loss of desmoplakin tail causes lethal acantholytic epidermolysis bullosa."
Jonkman M.F., Pasmooij A.M.G., Pasmans S.G.M.A., van den Berg M.P., Ter Horst H.J., Timmer A., Pas H.H.
Am. J. Hum. Genet. 77:653-660(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN LETHAL ACANTHOLYTIC EPIDERMOLYSIS BULLOSA.
[32]"Clinical profile of four families with arrhythmogenic right ventricular cardiomyopathy caused by dominant desmoplakin mutations."
Bauce B., Basso C., Rampazzo A., Beffagna G., Daliento L., Frigo G., Malacrida S., Settimo L., Danieli G., Thiene G., Nava A.
Eur. Heart J. 26:1666-1675(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARVD8 ARG-299; LYS-1255 AND ILE-1775.
[33]"Comprehensive desmosome mutation analysis in North Americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy."
den Haan A.D., Tan B.Y., Zikusoka M.N., Llado L.I., Jain R., Daly A., Tichnell C., James C., Amat-Alarcon N., Abraham T., Russell S.D., Bluemke D.A., Calkins H., Dalal D., Judge D.P.
Circ. Cardiovasc. Genet. 2:428-435(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARVD8 ARG-299; LYS-1255 AND ILE-1775, VARIANTS PHE-305; VAL-1505; CYS-1512; LYS-1526; CYS-1537 AND GLN-1738.
[34]"Role of genetic testing in arrhythmogenic right ventricular cardiomyopathy/dysplasia."
Barahona-Dussault C., Benito B., Campuzano O., Iglesias A., Leung T.L., Robb L., Talajic M., Brugada R.
Clin. Genet. 77:37-48(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHE-305; CYS-1512; LYS-1526; CYS-1537; CYS-1537; GLN-1738 AND VAL-1833.
+Additional computationally mapped references.

Web resources

Wikipedia

Desmoplakin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M77830 mRNA. Translation: AAA85135.1.
HM151899 mRNA. Translation: ADI58529.1.
AL031058 Genomic DNA. Translation: CAA19927.1.
BC140802 mRNA. Translation: AAI40803.1.
J05211 mRNA. Translation: AAA35766.1.
AF139065 mRNA. Translation: AAF19785.1.
CCDSCCDS4501.1. [P15924-1]
CCDS47368.1. [P15924-2]
PIRA38194.
RefSeqNP_001008844.1. NM_001008844.1. [P15924-2]
NP_004406.2. NM_004415.2. [P15924-1]
UniGeneHs.519873.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LM5X-ray1.80A/B2609-2822[»]
1LM7X-ray3.00A/B2209-2456[»]
3R6NX-ray2.95A/B178-627[»]
ProteinModelPortalP15924.
SMRP15924. Positions 178-627, 2209-2448, 2613-2808.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108166. 53 interactions.
DIPDIP-109N.
IntActP15924. 21 interactions.
MINTMINT-1157663.
STRING9606.ENSP00000369129.

PTM databases

PhosphoSiteP15924.

Polymorphism databases

DMDM115502381.

Proteomic databases

MaxQBP15924.
PaxDbP15924.
PeptideAtlasP15924.
PRIDEP15924.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379802; ENSP00000369129; ENSG00000096696. [P15924-1]
ENST00000418664; ENSP00000396591; ENSG00000096696. [P15924-2]
GeneID1832.
KEGGhsa:1832.
UCSCuc003mxp.1. human. [P15924-1]
uc003mxq.1. human. [P15924-2]

Organism-specific databases

CTD1832.
GeneCardsGC06P007541.
GeneReviewsDSP.
HGNCHGNC:3052. DSP.
HPACAB037324.
MIM125647. gene.
605676. phenotype.
607450. phenotype.
607655. phenotype.
609638. phenotype.
612908. phenotype.
neXtProtNX_P15924.
Orphanet293899. Familial isolated arrhythmogenic ventricular dysplasia, biventricular form.
293888. Familial isolated arrhythmogenic ventricular dysplasia, left dominant form.
293910. Familial isolated arrhythmogenic ventricular dysplasia, right dominant form.
2032. Idiopathic pulmonary fibrosis.
50942. Keratosis palmoplantaris striata.
158687. Lethal acantholytic epidermolysis bullosa.
293165. Skin fragility-woolly hair-palmoplantar keratoderma syndrome.
65282. Woolly hair-palmoplantar keratoderma-dilated cardiomyopathy syndrome.
PharmGKBPA27505.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG12793.
HOGENOMHOG000112198.
HOVERGENHBG081434.
InParanoidP15924.
KOK10381.
OMAKRSMSFQ.
OrthoDBEOG7TQTZV.
PhylomeDBP15924.
TreeFamTF106435.

Enzyme and pathway databases

ReactomeREACT_578. Apoptosis.

Gene expression databases

ArrayExpressP15924.
BgeeP15924.
CleanExHS_DSP.
GenevestigatorP15924.

Family and domain databases

Gene3D3.90.1290.10. 5 hits.
InterProIPR028462. Desmoplakin.
IPR001101. Plectin_repeat.
IPR018159. Spectrin/alpha-actinin.
[Graphical view]
PANTHERPTHR11915:SF234. PTHR11915:SF234. 1 hit.
PfamPF00681. Plectin. 8 hits.
[Graphical view]
SMARTSM00250. PLEC. 18 hits.
SM00150. SPEC. 3 hits.
[Graphical view]
SUPFAMSSF75399. SSF75399. 5 hits.
ProtoNetSearch...

Other

ChiTaRSDSP. human.
EvolutionaryTraceP15924.
GeneWikiDesmoplakin.
GenomeRNAi1832.
NextBio35495766.
PROP15924.
SOURCESearch...

Entry information

Entry nameDESP_HUMAN
AccessionPrimary (citable) accession number: P15924
Secondary accession number(s): B2RTT2 expand/collapse secondary AC list , D7RX09, O75993, Q14189, Q9UHN4
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: October 3, 2006
Last modified: July 9, 2014
This is version 181 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM