Summary: Members of the armadillo family of proteins that are found in DESMOSOMES and interact with various proteins including desmocadherins; DESMOPLAKIN; ACTIN FILAMENTS; and KERATINS.

Top Publications

  1. Mertens C, Kuhn C, Franke W. Plakophilins 2a and 2b: constitutive proteins of dual location in the karyoplasm and the desmosomal plaque. J Cell Biol. 1996;135:1009-25 pubmed
    ..We conclude that plakophilins 2a and 2b are basic nuclear proteins that in certain cell types additionally assemble with other proteins to ..
  2. Syrris P, Ward D, Asimaki A, Sen Chowdhry S, Ebrahim H, Evans A, et al. Clinical expression of plakophilin-2 mutations in familial arrhythmogenic right ventricular cardiomyopathy. Circulation. 2006;113:356-64 pubmed
  3. Bass Zubek A, Godsel L, Delmar M, Green K. Plakophilins: multifunctional scaffolds for adhesion and signaling. Curr Opin Cell Biol. 2009;21:708-16 pubmed publisher
    Armadillo family proteins known as plakophilins have been characterized as structural components of desmosomes that stabilize and strengthen adhesion by enhancing attachments with the intermediate filament cytoskeleton...
  4. Hatzfeld M, Haffner C, Schulze K, Vinzens U. The function of plakophilin 1 in desmosome assembly and actin filament organization. J Cell Biol. 2000;149:209-22 pubmed
  5. Christensen A, Benn M, Bundgaard H, Tybjaerg Hansen A, Haunso S, Svendsen J. Wide spectrum of desmosomal mutations in Danish patients with arrhythmogenic right ventricular cardiomyopathy. J Med Genet. 2010;47:736-44 pubmed publisher
    ..Our study supports comprehensive desmosomal mutation screening beyond the first encountered mutation, whereas routine screening for genomic rearrangements does not seem indicated. ..
  6. Wolf A, Keil R, Götzl O, Mun A, Schwarze K, Lederer M, et al. The armadillo protein p0071 regulates Rho signalling during cytokinesis. Nat Cell Biol. 2006;8:1432-40 pubmed
    ..These findings support an essential role for p0071 in spatially regulating restricted Rho signalling during cytokinesis. ..
  7. Aigner K, Descovich L, Mikula M, Sultan A, Dampier B, Bonne S, et al. The transcription factor ZEB1 (deltaEF1) represses Plakophilin 3 during human cancer progression. FEBS Lett. 2007;581:1617-24 pubmed
    ..Hence, the transcriptional repression of PKP3 by ZEB1 contributes to ZEB1-mediated disintegration of intercellular adhesion and epithelial to mesenchymal transition. ..
  8. Antoniades L, Tsatsopoulou A, Anastasakis A, Syrris P, Asimaki A, Panagiotakos D, et al. Arrhythmogenic right ventricular cardiomyopathy caused by deletions in plakophilin-2 and plakoglobin (Naxos disease) in families from Greece and Cyprus: genotype-phenotype relations, diagnostic features and prognosis. Eur Heart J. 2006;27:2208-16 pubmed
    ..Non-invasive family screening may largely be based on T-wave inversion, right ventricular wall motion abnormalities, and frequent ventricular extrasystoles to identify mutation carriers. ..
  9. Furukawa C, Daigo Y, Ishikawa N, Kato T, Ito T, Tsuchiya E, et al. Plakophilin 3 oncogene as prognostic marker and therapeutic target for lung cancer. Cancer Res. 2005;65:7102-10 pubmed

More Information


  1. Kami K, Chidgey M, Dafforn T, Overduin M. The desmoglein-specific cytoplasmic region is intrinsically disordered in solution and interacts with multiple desmosomal protein partners. J Mol Biol. 2009;386:531-43 pubmed publisher
    ..Thus, the DSCR is an intrinsically disordered functional domain with an inducible structure that, along with the membrane proximal region, forms a flexible scaffold for cytoplasmic assembly at the desmosome. ..
  2. Bonne S, van Hengel J, van Roy F. Chromosomal mapping of human armadillo genes belonging to the p120(ctn)/plakophilin subfamily. Genomics. 1998;51:452-4 pubmed
    ..Although some of the Armadillo proteins are highly related to one another, the corresponding genes are dispersed throughout the human genome. ..
  3. Whittock N, Haftek M, Angoulvant N, Wolf F, Perrot H, Eady R, et al. Genomic amplification of the human plakophilin 1 gene and detection of a new mutation in ectodermal dysplasia/skin fragility syndrome. J Invest Dermatol. 2000;115:368-74 pubmed
    ..These results expand the database of plakophilin 1 mutations and demonstrate the importance of this protein in the stabilization of desmosomal adhesion in terminally differentiating keratinocytes. ..
  4. South A, Wan H, Stone M, Dopping Hepenstal P, Purkis P, Marshall J, et al. Lack of plakophilin 1 increases keratinocyte migration and reduces desmosome stability. J Cell Sci. 2003;116:3303-14 pubmed
    ..Thus, plakophilin 1 has a key role in increasing desmosomal protein content, in desmosome assembly, and in regulating cell migration. ..
  5. Hatzfeld M, Nachtsheim C. Cloning and characterization of a new armadillo family member, p0071, associated with the junctional plaque: evidence for a subfamily of closely related proteins. J Cell Sci. 1996;109 ( Pt 11):2767-78 pubmed
    ..We therefore suggest that family members exert similar functions and might be involved in cell signalling through cell contacts. ..
  6. Asimaki A, Tandri H, Huang H, Halushka M, Gautam S, Basso C, et al. A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy. N Engl J Med. 2009;360:1075-84 pubmed publisher
    ..Routine immunohistochemical analysis of a conventional endomyocardial-biopsy sample appears to be a highly sensitive and specific diagnostic test for ARVC. ..
  7. Klymkowsky M. Plakophilin, armadillo repeats, and nuclear localization. Microsc Res Tech. 1999;45:43-54 pubmed
    b>Plakophilins are armadillo-repeat containing proteins, identified through their localization to desmosomes. Expressed in a wide range of tissues, plakophilins are largely nuclear in most cell types [Schmidt et al...
  8. Sobolik Delmaire T, Katafiasz D, Wahl J. Carboxyl terminus of Plakophilin-1 recruits it to plasma membrane, whereas amino terminus recruits desmoplakin and promotes desmosome assembly. J Biol Chem. 2006;281:16962-70 pubmed
    b>Plakophilins are armadillo repeat-containing proteins, initially identified as desmosomal plaque proteins that have subsequently been shown to also localize to the nucleus...
  9. Kundu S, Gosavi P, Khapare N, Patel R, Hosing A, Maru G, et al. Plakophilin3 downregulation leads to a decrease in cell adhesion and promotes metastasis. Int J Cancer. 2008;123:2303-14 pubmed publisher
    ..These data indicate that plakophilin3 loss leads to a decrease in cell-cell adhesion leading to the stimulation of neoplastic progression and metastasis. ..
  10. Franke W, Borrmann C, Grund C, Pieperhoff S. The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins. Eur J Cell Biol. 2006;85:69-82 pubmed
  11. Bhuiyan Z, Jongbloed J, van der Smagt J, Lombardi P, Wiesfeld A, Nelen M, et al. Desmoglein-2 and desmocollin-2 mutations in dutch arrhythmogenic right ventricular dysplasia/cardiomypathy patients: results from a multicenter study. Circ Cardiovasc Genet. 2009;2:418-27 pubmed publisher
    ..Negative T waves on ECG were prevalent among mutation carriers (P<0.002). ..
  12. den Haan A, Tan B, Zikusoka M, Lladó L, Jain R, Daly A, et al. Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Cardiovasc Genet. 2009;2:428-35 pubmed publisher
    ..Compared with those without a desmosome gene mutation, individuals with a desmosome gene mutation had earlier-onset ARVD/C and were more likely to have ventricular tachycardia. ..
  13. Wolf A, Hatzfeld M. A role of plakophilins in the regulation of translation. Cell Cycle. 2010;9:2973-8 pubmed publisher
    b>Plakophilins 1-3 are members of the p120(ctn)-family of armadillo related proteins...
  14. Wu S, Wang P, Hou Y, Zhang X, Shan Z, Yu X, et al. Mutation of plakophilin-2 gene in arrhythmogenic right ventricular cardiomyopathy. Chin Med J (Engl). 2009;122:403-7 pubmed
    ..05). We discovered a plakophilin-2 mutation that prolongs the QT interval dispersion in the southern Chinese ARVC population. ..
  15. Lahtinen A, Lehtonen A, Kaartinen M, Toivonen L, Swan H, Widen E, et al. Plakophilin-2 missense mutations in arrhythmogenic right ventricular cardiomyopathy. Int J Cardiol. 2008;126:92-100 pubmed
    ..Our preliminary data also suggest that ultrastructural cell junction abnormalities may associate with plakophilin-2 mutations. ..
  16. Bass Zubek A, Hobbs R, Amargo E, Garcia N, Hsieh S, Chen X, et al. Plakophilin 2: a critical scaffold for PKC alpha that regulates intercellular junction assembly. J Cell Biol. 2008;181:605-13 pubmed publisher
    b>Plakophilins (PKPs) are armadillo family members related to the classical cadherin-associated protein p120(ctn)...
  17. Hatzfeld M, Kristjansson G, Plessmann U, Weber K. Band 6 protein, a major constituent of desmosomes from stratified epithelia, is a novel member of the armadillo multigene family. J Cell Sci. 1994;107 ( Pt 8):2259-70 pubmed
    ..The amino-terminal region of B6P (residues 1 to 263) shows no significant homology to any known protein sequence. It may therefore be involved in unique functions of B6P. ..
  18. Breuninger S, Reidenbach S, Sauer C, Strobel P, Pfitzenmaier J, Trojan L, et al. Desmosomal plakophilins in the prostate and prostatic adenocarcinomas: implications for diagnosis and tumor progression. Am J Pathol. 2010;176:2509-19 pubmed publisher
    The plakophilins, members of the armadillo-repeat family, consist of three different proteins (PKP1-3) that are specifically recruited to desmosomal plaques in a highly cell type-specific manner...
  19. Rickelt S, Rizzo S, Doerflinger Y, Zentgraf H, Basso C, Gerosa G, et al. A novel kind of tumor type-characteristic junction: plakophilin-2 as a major protein of adherens junctions in cardiac myxomata. Mod Pathol. 2010;23:1429-37 pubmed publisher
    ..We propose to examine the marker value of Pkp2 in clinical diagnoses of cardiac myxomata and to develop Pkp2-targeted therapeutic reagents...
  20. Hofmann I, Casella M, Schnolzer M, Schlechter T, Spring H, Franke W. Identification of the junctional plaque protein plakophilin 3 in cytoplasmic particles containing RNA-binding proteins and the recruitment of plakophilins 1 and 3 to stress granules. Mol Biol Cell. 2006;17:1388-98 pubmed
    ..Our results show that cytoplasmic PKP3 is constitutively associated with RNA-binding proteins and indicate an involvement in processes of translation and RNA metabolism. ..
  21. Schmidt A, Jäger S. Plakophilins--hard work in the desmosome, recreation in the nucleus?. Eur J Cell Biol. 2005;84:189-204 pubmed
    ..least three different types of proteins are found in the desmosomal plaque, one of which is represented by the plakophilins, a recently described sub-family of sequence-related armadillo-repeat proteins...
  22. Muller J, Ritt D, Copeland T, Morrison D. Functional analysis of C-TAK1 substrate binding and identification of PKP2 as a new C-TAK1 substrate. EMBO J. 2003;22:4431-42 pubmed
    ..Phosphorylation of PKP2 by C-TAK1 also generates a 14-3-3-binding site that influences PKP2 localization. These findings underscore the importance of C-TAK1 as a regulator of 14-3-3 binding and protein localization. ..
  23. Cox M, van der Smagt J, Noorman M, Wiesfeld A, Volders P, van Langen I, et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy diagnostic task force criteria: impact of new task force criteria. Circ Arrhythm Electrophysiol. 2010;3:126-33 pubmed publisher
    ..ECG criteria and pathogenic mutations especially contributed to new diagnosis. Newly proposed TFC have a major impact in increasing diagnostic yield of ARVD/C. ..
  24. Rickelt S, Winter Simanowski S, Noffz E, Kuhn C, Franke W. Upregulation of plakophilin-2 and its acquisition to adherens junctions identifies a novel molecular ensemble of cell-cell-attachment characteristic for transformed mesenchymal cells. Int J Cancer. 2009;125:2036-48 pubmed publisher
    ..We propose to examine its presence in transformed mesenchymal cells and related tumors and to use it as an additional diagnostic criterion. ..
  25. McMillan J, Haftek M, Akiyama M, South A, Perrot H, McGrath J, et al. Alterations in desmosome size and number coincide with the loss of keratinocyte cohesion in skin with homozygous and heterozygous defects in the desmosomal protein plakophilin 1. J Invest Dermatol. 2003;121:96-103 pubmed
    ..These findings attest to the molecular recruiting and stabilizing roles of PkP1 in desmosome formation, particularly in the LSB compartment. ..
  26. Qiu X, Liu W, Hu D, Zhu T, Li C, Li L, et al. Mutations of plakophilin-2 in Chinese with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Am J Cardiol. 2009;103:1439-44 pubmed publisher
    ..No significant difference was found in phenotype characteristics between patients with ARVD/C with and without PKP2 mutations. The decreased penetrance indicated that an ARVD/C diagnosis cannot solely rely on genotyping results. ..
  27. Keil R, Wolf A, Huttelmaier S, Hatzfeld M. Beyond regulation of cell adhesion: local control of RhoA at the cleavage furrow by the p0071 catenin. Cell Cycle. 2007;6:122-7 pubmed
    ..subfamily of armadillo proteins that also comprises p0071, delta-catenin, ARVCF and the more distantly related plakophilins 1-3...
  28. Setzer S, Calkins C, Garner J, Summers S, Green K, Kowalczyk A. Comparative analysis of armadillo family proteins in the regulation of a431 epithelial cell junction assembly, adhesion and migration. J Invest Dermatol. 2004;123:426-33 pubmed
    ..armadillo family protein related to both the adherens junction protein p120ctn and to the desmosomal proteins plakophilins 1-3...
  29. Fressart V, Duthoit G, Donal E, Probst V, Deharo J, Chevalier P, et al. Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice. Europace. 2010;12:861-8 pubmed publisher
    ..We wanted to address the potential impact of genotyping...
  30. Calkins C, Hoepner B, Law C, Novak M, Setzer S, Hatzfeld M, et al. The Armadillo family protein p0071 is a VE-cadherin- and desmoplakin-binding protein. J Biol Chem. 2003;278:1774-83 pubmed
  31. Demirag G, Sullu Y, Gurgenyatagi D, Okumus N, Yucel I. Expression of plakophilins (PKP1, PKP2, and PKP3) in gastric cancers. Diagn Pathol. 2011;6:1 pubmed publisher
    ..junction proteins (including armadillo proteins) in tumor biology is known, but limited with regard to plakophilins. We explored the relationship between plakophilins (PKP1, PKP2, PKP3) to gastric cancer via immunohistochemical ..
  32. Demirag G, Sullu Y, Yucel I. Expression of Plakophilins (PKP1, PKP2, and PKP3) in breast cancers. Med Oncol. 2012;29:1518-22 pubmed publisher
    b>Plakophilins (PKP) are desmosomal plague proteins, which belong to the p120ctn subfamily of armadillo repeat containing proteins. We aimed to analyze the role of plakophilins in breast cancer and its clinical progress...
  33. Hofmann I, Mertens C, Brettel M, Nimmrich V, Schnolzer M, Herrmann H. Interaction of plakophilins with desmoplakin and intermediate filament proteins: an in vitro analysis. J Cell Sci. 2000;113 ( Pt 13):2471-83 pubmed
    ..We postulate that (1) effective cellular regulatory mechanisms exist that prevent plakophilins from unscheduled IF-binding, and (2) specific desmoplakin interactions with either PKP1, PKP2 or PKP3, or ..
  34. Al Amoudi A, Castaño Diez D, Devos D, Russell R, Johnson G, Frangakis A. The three-dimensional molecular structure of the desmosomal plaque. Proc Natl Acad Sci U S A. 2011;108:6480-5 pubmed publisher
    ..b>Plakophilins are added as a molecular reinforcement to fill the gap between the formed plaque complexes and the plasma ..
  35. Petrof G, Mellerio J, McGrath J. Desmosomal genodermatoses. Br J Dermatol. 2012;166:36-45 pubmed publisher
  36. Kirchner F, Schuetz A, Boldt L, Martens K, Dittmar G, Haverkamp W, et al. Molecular insights into arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 missense mutations. Circ Cardiovasc Genet. 2012;5:400-11 pubmed publisher
  37. Steijlen P, van Steensel M, Jansen B, Blokx W, van de Kerkhof P, Happle R, et al. Cryptic splicing at a non-consensus splice-donor in a patient with a novel mutation in the plakophilin-1 gene. J Invest Dermatol. 2004;122:1321-4 pubmed
  38. Tsatsopoulou A, Protonotarios N, McKenna W. Arrhythmogenic right ventricular dysplasia, a cell adhesion cardiomyopathy: insights into disease pathogenesis from preliminary genotype--phenotype assessment. Heart. 2006;92:1720-3 pubmed
    ..The interesting finding of abnormal distribution of plakoglobin, independently of the primarily affected protein, might suggest a common pathway for plakoglobin in ARVC pathogenesis. ..
  39. Pieperhoff S, Franke W. The area composita of adhering junctions connecting heart muscle cells of vertebrates. VI. Different precursor structures in non-mammalian species. Eur J Cell Biol. 2008;87:413-30 pubmed publisher
  40. Sen Chowdhry S, Syrris P, McKenna W. Role of genetic analysis in the management of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol. 2007;50:1813-21 pubmed
  41. Sen Chowdhry S, Syrris P, Ward D, Asimaki A, Sevdalis E, McKenna W. Clinical and genetic characterization of families with arrhythmogenic right ventricular dysplasia/cardiomyopathy provides novel insights into patterns of disease expression. Circulation. 2007;115:1710-20 pubmed
    ..Recognition of disease variants with early and/or predominant LV involvement supports adoption of the broader term arrhythmogenic cardiomyopathy. ..
  42. Christensen A, Benn M, Tybjaerg Hansen A, Haunso S, Svendsen J. Missense variants in plakophilin-2 in arrhythmogenic right ventricular cardiomyopathy patients--disease-causing or innocent bystanders?. Cardiology. 2010;115:148-54 pubmed publisher
    ..We recommend conservative interpretation of missense variants in PKP2, functional characterization and large-scale sequencing to clarify normal variation in the gene. ..
  43. Bauce B, Nava A, Beffagna G, Basso C, Lorenzon A, Smaniotto G, et al. Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Heart Rhythm. 2010;7:22-9 pubmed publisher
    ..Even if multiple-mutation carriers show a wide variability in clinical expression, the extent of the disease is higher compared to that in single-mutation carriers. ..
  44. Watkins D, Hendricks N, Shaboodien G, Mbele M, Parker M, Vezi B, et al. Clinical features, survival experience, and profile of plakophylin-2 gene mutations in participants of the arrhythmogenic right ventricular cardiomyopathy registry of South Africa. Heart Rhythm. 2009;6:S10-7 pubmed publisher
    ..PKP2 gene mutations are common, have an allele dose effect, and a novel founder effect in white South Africans. ..
  45. Barth M, Schumacher H, Kuhn C, Akhyari P, Lichtenberg A, Franke W. Cordial connections: molecular ensembles and structures of adhering junctions connecting interstitial cells of cardiac valves in situ and in cell culture. Cell Tissue Res. 2009;337:63-77 pubmed publisher
  46. Gerull B, Heuser A, Wichter T, Paul M, Basson C, McDermott D, et al. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet. 2004;36:1162-4 pubmed
    ..In two kindreds with ARVC, disease was incompletely penetrant in most carriers of PKP2 mutations...
  47. Sobolik Delmaire T, Reddy R, Pashaj A, Roberts B, Wahl J. Plakophilin-1 localizes to the nucleus and interacts with single-stranded DNA. J Invest Dermatol. 2010;130:2638-46 pubmed publisher
    b>Plakophilins (Pkp-1, -2, and -3) comprise a family of armadillo repeat-containing proteins first identified as desmosomal plaque components, in which they link desmoplakin to the desmosomal cadherins...
  48. Wessagowit V, McGrath J. Clinical and molecular significance of splice site mutations in the plakophilin 1 gene in patients with ectodermal dysplasia-skin fragility syndrome. Acta Derm Venereol. 2005;85:386-8 pubmed
  49. Green K, Gaudry C. Are desmosomes more than tethers for intermediate filaments?. Nat Rev Mol Cell Biol. 2000;1:208-16 pubmed
    ..But desmosomes have also recently been recognized as sensors that respond to environmental and cellular cues by modulating their assembly state and, possibly, their signalling functions. ..
  50. Elliott P, O Mahony C, Syrris P, Evans A, Rivera Sorensen C, Sheppard M, et al. Prevalence of desmosomal protein gene mutations in patients with dilated cardiomyopathy. Circ Cardiovasc Genet. 2010;3:314-22 pubmed publisher
    ..This study suggests that both clinical presentations can be caused by mutations in desmosomal protein genes. ..
  51. Gandjbakhch E, Charron P, Fressart V, Lorin de la Grandmaison G, Simon F, Gary F, et al. Plakophilin 2A is the dominant isoform in human heart tissue: consequences for the genetic screening of arrhythmogenic right ventricular cardiomyopathy. Heart. 2011;97:844-9 pubmed publisher
    ..Variant splicing also has important consequences for the interpretation of mutation analysis and genetic counselling in ARVC and other hereditary cardiac diseases. ..
  52. Kannankeril P, Bhuiyan Z, Darbar D, Mannens M, Wilde A, Roden D. Arrhythmogenic right ventricular cardiomyopathy due to a novel plakophilin 2 mutation: wide spectrum of disease in mutation carriers within a family. Heart Rhythm. 2006;3:939-44 pubmed
    ..Premature truncation of the plakophilin-2 protein appears to be the predominant mechanism whereby PKP2 mutations elicit the ARVC phenotype. ..
  53. Awad M, Dalal D, Tichnell C, James C, Tucker A, Abraham T, et al. Recessive arrhythmogenic right ventricular dysplasia due to novel cryptic splice mutation in PKP2. Hum Mutat. 2006;27:1157 pubmed
    ..The possibility of cryptic or alternative splicing should be considered with identification of apparently synonymous nucleotide substitutions in this gene. ..