Summary: A group of desmosomal cadherins with cytoplasmic tails that are divergent from those of classical CADHERINS. Their intracytoplasmic domains bind PLAKOGLOBIN; PLAKOPHILINS; and DESMOPLAKINS.

Top Publications

  1. Ishida Yamamoto A, Igawa S, Kishibe M. Order and disorder in corneocyte adhesion. J Dermatol. 2011;38:645-54 pubmed publisher
    ..Abnormal corneodesmosome degradation is also found in more common skin diseases including ichthyosis vulgaris, atopic dermatitis, psoriasis vulgaris, lichen planus and soap-induced xerosis...
  2. Chidgey M, Yue K, Gould S, Byrne C, Garrod D. Changing pattern of desmocollin 3 expression accompanies epidermal organisation during skin development. Dev Dyn. 1997;210:315-27 pubmed
    The adhesive core of the desmosome is composed of cadherin-like glycoproteins of 2 families, desmocollins and desmogleins...
  3. Kowalczyk A, Bornslaeger E, Borgwardt J, Palka H, Dhaliwal A, Corcoran C, et al. The amino-terminal domain of desmoplakin binds to plakoglobin and clusters desmosomal cadherin-plakoglobin complexes. J Cell Biol. 1997;139:773-84 pubmed
    ..Desmosomes contain two classes of cadherins, desmogleins, and desmocollins, that bind to the cytoplasmic protein plakoglobin...
  4. Kurzen H, Münzing I, Hartschuh W. Expression of desmosomal proteins in squamous cell carcinomas of the skin. J Cutan Pathol. 2003;30:621-30 pubmed
    ..Plakophilin 1, desmoglein 1, and the desmocollins 1-3 were found to be heterogeneously expressed in all neoplasms without significant correlation to aggressive ..
  5. Oshiro M, Watts G, Wozniak R, Junk D, Munoz Rodriguez J, Domann F, et al. Mutant p53 and aberrant cytosine methylation cooperate to silence gene expression. Oncogene. 2003;22:3624-34 pubmed
    ..These results suggest that cancer treatments that target both genetic and epigenetic facets of gene regulation may be a useful strategy towards the therapeutic transcriptional reprogramming of cancer cells. ..
  6. Alazawi W, Morris L, Stanley M, Garrod D, Coleman N. Altered expression of desmosomal components in high-grade squamous intraepithelial lesions of the cervix. Virchows Arch. 2003;443:51-6 pubmed
  7. Smith E, Fuchs E. Defining the interactions between intermediate filaments and desmosomes. J Cell Biol. 1998;141:1229-41 pubmed
    ..As epidermal cells differentiate, PP1 is added as a molecular reinforcement to the plaque, enhancing anchorage to IFs and accounting at least partially for the increase in numbers and stability of desmosomes in suprabasal cells. ..
  8. Troyanovsky S, Troyanovsky R, Eshkind L, Leube R, Franke W. Identification of amino acid sequence motifs in desmocollin, a desmosomal glycoprotein, that are required for plakoglobin binding and plaque formation. Proc Natl Acad Sci U S A. 1994;91:10790-4 pubmed
    ..harbor, in a mutually exclusive pattern, the information for assembly of the IF-anchoring desmosomal plaque in desmocollins and for formation of the alpha-/beta-catenin- and vinculin-containing, actin filament-anchoring plaque in E- ..
  9. Düker I, Schaller J, Rose C, Zillikens D, Hashimoto T, Kunze J. Subcorneal pustular dermatosis-type IgA pemphigus with autoantibodies to desmocollins 1, 2, and 3. Arch Dermatol. 2009;145:1159-62 pubmed publisher
    ..Because pemphigus seems to be a heterogeneous disorder, further studies are needed to evaluate the complexity of the disease. ..

More Information


  1. De Bortoli M, Beffagna G, Bauce B, Lorenzon A, Smaniotto G, Rigato I, et al. The p.A897KfsX4 frameshift variation in desmocollin-2 is not a causative mutation in arrhythmogenic right ventricular cardiomyopathy. Eur J Hum Genet. 2010;18:776-82 pubmed publisher
  2. Gehmlich K, Syrris P, Peskett E, Evans A, Ehler E, Asimaki A, et al. Mechanistic insights into arrhythmogenic right ventricular cardiomyopathy caused by desmocollin-2 mutations. Cardiovasc Res. 2011;90:77-87 pubmed publisher
    ..However, the underlying molecular processes are poorly understood...
  3. Mechanic S, Raynor K, Hill J, Cowin P. Desmocollins form a distinct subset of the cadherin family of cell adhesion molecules. Proc Natl Acad Sci U S A. 1991;88:4476-80 pubmed
    The desmosomal adhesive core is formed by four major components: desmoglein (Mr, 165,000), desmocollins I and II (Mr, 120,000 and 110,000, respectively), and a Mr 22,000 protein...
  4. Collins J, Legan P, Kenny T, MacGarvie J, Holton J, Garrod D. Cloning and sequence analysis of desmosomal glycoproteins 2 and 3 (desmocollins): cadherin-like desmosomal adhesion molecules with heterogeneous cytoplasmic domains. J Cell Biol. 1991;113:381-91 pubmed
    Desmosomal glycoproteins 2 and 3 (dg2 and 3) or desmocollins have been implicated in desmosome adhesion. We have obtained a 5.0-kb-long clone for dg3 from a bovine nasal epidermal lambda gt11 cDNA library...
  5. Gehmlich K, Lambiase P, Asimaki A, Ciaccio E, Ehler E, Syrris P, et al. A novel desmocollin-2 mutation reveals insights into the molecular link between desmosomes and gap junctions. Heart Rhythm. 2011;8:711-8 pubmed publisher
    ..In particular, the newly identified interaction between the desmocollin-2a isoform and connexin43 provides novel insights into the molecular link between desmosomes and gap junctions. ..
  6. Windoffer R, Borchert Stuhlträger M, Leube R. Desmosomes: interconnected calcium-dependent structures of remarkable stability with significant integral membrane protein turnover. J Cell Sci. 2002;115:1717-32 pubmed
    ..Taken together, our observations suggest that desmosomes are pliable structures capable of fine adjustment to functional demands despite their overall structural stability and relative immobility. ..
  7. Merritt A, Berika M, Zhai W, Kirk S, Ji B, Hardman M, et al. Suprabasal desmoglein 3 expression in the epidermis of transgenic mice results in hyperproliferation and abnormal differentiation. Mol Cell Biol. 2002;22:5846-58 pubmed
    ..Our results contrast markedly with those recently obtained by expressing Dsg3 in epidermis under the involucrin promoter. Possible reasons for this difference are considered in this paper. ..
  8. Cui T, Chen Y, Yang L, Mireskandari M, Knösel T, Zhang Q, et al. Diagnostic and prognostic impact of desmocollins in human lung cancer. J Clin Pathol. 2012;65:1100-6 pubmed publisher
    ..Two main members of desmosomal cadherins, desmogleins (DSGs) and desmocollins (DSCs), are involved in carcinogenesis. However, their role in human lung cancer remained elusive...
  9. Ishii K, Norvell S, Bannon L, Amargo E, Pascoe L, Green K. Assembly of desmosomal cadherins into desmosomes is isoform dependent. J Invest Dermatol. 2001;117:26-35 pubmed
    ..contain multiple representatives of the desmosomal cadherin family, which includes three desmogleins and three desmocollins. Rules governing the assembly of desmosomal cadherin isoforms into desmosomes of different cell types are ..
  10. Caubet C, Jonca N, Brattsand M, Guerrin M, Bernard D, Schmidt R, et al. Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. J Invest Dermatol. 2004;122:1235-44 pubmed
    ..These results strongly suggest that the two kalikreins are involved in desquamation. A model is proposed for desquamation that could be regulated by a precisely controlled protease-protease inhibitor balance. ..
  11. Oshiro M, Kim C, Wozniak R, Junk D, Munoz Rodriguez J, Burr J, et al. Epigenetic silencing of DSC3 is a common event in human breast cancer. Breast Cancer Res. 2005;7:R669-80 pubmed
  12. Wang L, Liu T, Wang Y, Cao L, Nishioka M, Aguirre R, et al. Altered expression of desmocollin 3, desmoglein 3, and beta-catenin in oral squamous cell carcinoma: correlation with lymph node metastasis and cell proliferation. Virchows Arch. 2007;451:959-66 pubmed
  13. Awad M, Calkins H, Judge D. Mechanisms of disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Nat Clin Pract Cardiovasc Med. 2008;5:258-67 pubmed publisher
  14. Muller R, Heber B, Hashimoto T, Messer G, Mullegger R, Niedermeier A, et al. Autoantibodies against desmocollins in European patients with pemphigus. Clin Exp Dermatol. 2009;34:898-903 pubmed publisher
    ..Thus, IgG and IgA reactivity against Dsc was restricted to cases of PNP, IgA pemphigus and atypical pemphigus. These findings support the concept that desmocollins are not important autoantigens in PV.
  15. Barahona Dussault C, Benito B, Campuzano O, Iglesias A, Leung T, Robb L, et al. Role of genetic testing in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Clin Genet. 2010;77:37-48 pubmed publisher
  16. Gadhavi P, Greenwood M, Strom M, King I, Buxton R. The regulatory region of the human desmocollin 3 promoter forms a DNA four-way junction. Biochem Biophys Res Commun. 2001;281:520-8 pubmed
    Adhesion between desmosomal junctions is mediated by structural proteins of the cadherin family, viz. three desmocollins (DSC) and three desmogleins (DSG)...
  17. Arnemann J, Sullivan K, Magee A, King I, Buxton R. Stratification-related expression of isoforms of the desmosomal cadherins in human epidermis. J Cell Sci. 1993;104 ( Pt 3):741-50 pubmed
    Desmosomal junctions are abundant in epidermis and contain two classes of transmembrane glycoprotein, the desmocollins and the desmogleins, which are members of the cadherin superfamily of Ca(2+)-dependent cell adhesion molecules...
  18. Chitaev N, Troyanovsky S. Direct Ca2+-dependent heterophilic interaction between desmosomal cadherins, desmoglein and desmocollin, contributes to cell-cell adhesion. J Cell Biol. 1997;138:193-201 pubmed
    ..The observed specific coimmunoprecipitation of MPg by anti-Dsc antibodies in coculture indicates that an intercellular interaction between Dsc1 and Dsg is involved in cell-cell adhesion. ..
  19. King I, Angst B, Hunt D, Kruger M, Arnemann J, Buxton R. Hierarchical expression of desmosomal cadherins during stratified epithelial morphogenesis in the mouse. Differentiation. 1997;62:83-96 pubmed
    Desmosomes contain two heterogeneous families of specialized cadherins (desmogleins or Dsgs and desmocollins or Dscs), subtypes of which are known to be expressed in tissue-specific and differentiation-dependent patterns in adult ..
  20. Marcozzi C, Burdett I, Buxton R, Magee A. Coexpression of both types of desmosomal cadherin and plakoglobin confers strong intercellular adhesion. J Cell Sci. 1998;111 ( Pt 4):495-509 pubmed
    ..unique intercellular junctions in that they invariably contain two types of transmembrane cadherin molecule, desmocollins and desmogleins...
  21. Wahl JK3rd -, Nieset J, Sacco Bubulya P, Sadler T, Johnson K, Wheelock M. The amino- and carboxyl-terminal tails of (beta)-catenin reduce its affinity for desmoglein 2. J Cell Sci. 2000;113 ( Pt 10):1737-45 pubmed
    ..In the desmosome plakoglobin links the desmosomal cadherins, the desmogleins and the desmocollins, to the intermediate filament cytoskeleton. beta-catenin is not a component of the desmosome...
  22. Koch P, Goldschmidt M, Walsh M, Zimbelmann R, Schmelz M, Franke W. Amino acid sequence of bovine muzzle epithelial desmocollin derived from cloned cDNA: a novel subtype of desmosomal cadherins. Differentiation. 1991;47:29-36 pubmed
    ..The cDNA-deduced amino-acid sequence of desmocollin (presently we cannot decide to which of the two desmocollins, DC I or DC II, this clone relates) defines a polypeptide with a calculated molecular weight of 85,000, with a ..
  23. Arnemann J, Spurr N, Wheeler G, Parker A, Buxton R. Chromosomal assignment of the human genes coding for the major proteins of the desmosome junction, desmoglein DGI (DSG), desmocollins DGII/III (DSC), desmoplakins DPI/II (DSP), and plakoglobin DPIII (JUP). Genomics. 1991;10:640-5 pubmed
    ..major proteins of the desmosome type of cell junction, the desmosomal cadherins DGI (desmoglein) and DGII/III (desmocollins), and the plaque proteins DPI/II (desmoplakin) and DPIII (plakoglobin) and used them to test human-mouse and ..
  24. Hanakawa Y, Amagai M, Shirakata Y, Sayama K, Hashimoto K. Different effects of dominant negative mutants of desmocollin and desmoglein on the cell-cell adhesion of keratinocytes. J Cell Sci. 2000;113 ( Pt 10):1803-11 pubmed
    ..These findings lead us to speculate that Dsc interacts with components of the adherens junctions through beta-catenin, and plays a role in nucleating desmosomes after the adherens junctions have been established. ..
  25. Fang W, Gu W, Li E, Wu Z, Shen Z, SHEN J, et al. Reduced membranous and ectopic cytoplasmic expression of DSC2 in esophageal squamous cell carcinoma: an independent prognostic factor. Hum Pathol. 2010;41:1456-65 pubmed publisher
    ..These data suggest that desmocollin 2 is involved in the transformation and development of esophageal tumors and that desmocollin 2 expression level and intracellular localization may serve as a predictor for patient outcomes...
  26. 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...
  27. 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. ..
  28. 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. ..
  29. Troyanovsky S, Eshkind L, Troyanovsky R, Leube R, Franke W. Contributions of cytoplasmic domains of desmosomal cadherins to desmosome assembly and intermediate filament anchorage. Cell. 1993;72:561-74 pubmed
  30. Lorimer J, Hall L, Clarke J, Collins J, Fleming T, Garrod D. Cloning, sequence analysis and expression pattern of mouse desmocollin 2 (DSC2), a cadherin-like adhesion molecule. Mol Membr Biol. 1994;11:229-36 pubmed
    b>Desmocollins are cadherin-like adhesion molecules of desmosomes...
  31. Klus G, Rokaeus N, Bittner M, Chen Y, Korz D, Sukumar S, et al. Down-regulation of the desmosomal cadherin desmocollin 3 in human breast cancer. Int J Oncol. 2001;19:169-74 pubmed
  32. Funakoshi S, Ezaki T, Kong J, Guo R, Lynch J. Repression of the desmocollin 2 gene expression in human colon cancer cells is relieved by the homeodomain transcription factors Cdx1 and Cdx2. Mol Cancer Res. 2008;6:1478-90 pubmed publisher
    ..The regulation of desmosomal junctions by Cdx contributes to normal intestinal epithelial columnar morphology and likely antagonizes the epithelial-to-mesenchymal transition necessary for the metastasis of colon cancer cells in humans...
  33. Beffagna G, De Bortoli M, Nava A, Salamon M, Lorenzon A, Zaccolo M, et al. Missense mutations in desmocollin-2 N-terminus, associated with arrhythmogenic right ventricular cardiomyopathy, affect intracellular localization of desmocollin-2 in vitro. BMC Med Genet. 2007;8:65 pubmed
    ..Identification of additional DSC2 mutations associated with ARVC may result in increased diagnostic accuracy with implications for genetic counseling. ..
  34. Kowalczyk A, Palka H, Luu H, Nilles L, Anderson J, Wheelock M, et al. Posttranslational regulation of plakoglobin expression. Influence of the desmosomal cadherins on plakoglobin metabolic stability. J Biol Chem. 1994;269:31214-23 pubmed
    ..The desmosomal glycoproteins, desmogleins and desmocollins, are members of the cadherin family of adhesion molecules...
  35. Syed S, Trinnaman B, Martin S, Major S, Hutchinson J, Magee A. Molecular interactions between desmosomal cadherins. Biochem J. 2002;362:317-27 pubmed
    b>Desmocollins (Dscs) and desmogleins (Dsgs) are cell-adhesion molecules involved in the formation of desmosome cell-cell junctions and share structural similarities to classical cadherins such as E-cadherin...
  36. Hachem J, Wagberg F, Schmuth M, Crumrine D, Lissens W, Jayakumar A, et al. Serine protease activity and residual LEKTI expression determine phenotype in Netherton syndrome. J Invest Dermatol. 2006;126:1609-21 pubmed
    ..These studies provide a mechanistic basis for phenotypic variations in NS, and describe compensatory mechanisms that permit survival of NS patients in the face of unrelenting SP attack. ..
  37. Hardman M, Liu K, Avilion A, Merritt A, Brennan K, Garrod D, et al. Desmosomal cadherin misexpression alters beta-catenin stability and epidermal differentiation. Mol Cell Biol. 2005;25:969-78 pubmed
    ..Furthermore, the first function for a "b-type" desmocollin cadherin was demonstrated. ..
  38. Nuber U, Schafer S, Stehr S, Rackwitz H, Franke W. Patterns of desmocollin synthesis in human epithelia: immunolocalization of desmocollins 1 and 3 in special epithelia and in cultured cells. Eur J Cell Biol. 1996;71:1-13 pubmed
    ..specifically react, in immunoblot and immunolocalization experiments, with the human desmosomal cadherins, desmocollins Dsc1 (mAb Dsc1-U100) and Dsc3 (mAb Dsc3-U114), have allowed to study systematically the synthesis of these ..
  39. Heuser A, Plovie E, Ellinor P, Grossmann K, Shin J, Wichter T, et al. Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2006;79:1081-8 pubmed
    ..These data identify DSC2 mutations as a cause of ARVC in humans and demonstrate that physiologic levels of DSC2 are crucial for normal cardiac desmosome formation, early cardiac morphogenesis, and cardiac function. ..
  40. Hisamatsu Y, Amagai M, Garrod D, Kanzaki T, Hashimoto T. The detection of IgG and IgA autoantibodies to desmocollins 1-3 by enzyme-linked immunosorbent assays using baculovirus-expressed proteins, in atypical pemphigus but not in typical pemphigus. Br J Dermatol. 2004;151:73-83 pubmed
    ..This result indicates either that Dscs expressed by baculovirus may not adopt the correct conformation or that Dscs may need association with other molecules to express all the epitopes for autoantibodies. ..
  41. King I, Sullivan K, Bennett R, Buxton R. The desmocollins of human foreskin epidermis: identification and chromosomal assignment of a third gene and expression patterns of the three isoforms. J Invest Dermatol. 1995;105:314-21 pubmed
    ..The expression of the three human desmocollins was examined in foreskin epidermis by in situ hybridization with 3'-untranslated riboprobes and by ..
  42. Koch P, Goldschmidt M, Zimbelmann R, Troyanovsky R, Franke W. Complexity and expression patterns of the desmosomal cadherins. Proc Natl Acad Sci U S A. 1992;89:353-7 pubmed
    ..are intercellular junctions that contain two major kinds of transmembrane glycoproteins, desmoglein and desmocollins I and II, involved in cell-cell adhesion...
  43. Bannon L, Cabrera B, Stack M, Green K. Isoform-specific differences in the size of desmosomal cadherin/catenin complexes. J Invest Dermatol. 2001;117:1302-6 pubmed
    ..The transmembrane components of the desmosome, the desmogleins and desmocollins, are members of the cadherin family of cell-cell adhesion molecules...
  44. Parrish E, Marston J, Mattey D, Measures H, Venning R, Garrod D. Size heterogeneity, phosphorylation and transmembrane organisation of desmosomal glycoproteins 2 and 3 (desmocollins) in MDCK cells. J Cell Sci. 1990;96 ( Pt 2):239-48 pubmed
    ..and immunoprecipitation with specific antibodies to bovine desmosomal glycoproteins 2 and 3 (dg2 and dg3: desmocollins) reveals a triplet of polypeptides of Mr 115,000, 107,000 and 104,000 in MDCK cells...
  45. 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. ..
  46. Lorch J, Klessner J, Park J, Getsios S, Wu Y, Stack M, et al. Epidermal growth factor receptor inhibition promotes desmosome assembly and strengthens intercellular adhesion in squamous cell carcinoma cells. J Biol Chem. 2004;279:37191-200 pubmed
    ..Our results suggest that EGFR inhibition promotes desmosome assembly in oral squamous cell carcinoma cells, resulting in increased cell-cell adhesion. ..
  47. Getsios S, Amargo E, Dusek R, Ishii K, Sheu L, Godsel L, et al. Coordinated expression of desmoglein 1 and desmocollin 1 regulates intercellular adhesion. Differentiation. 2004;72:419-33 pubmed
    ..Collectively, these observations demonstrate that Dsg1 promotes the formation of intercellular adhesion complexes and suggest that the relative level of Dsg and Dsc expressed at the cell surface regulates this adhesive process. ..
  48. Nuber U, Schafer S, Schmidt A, Koch P, Franke W. The widespread human desmocollin Dsc2 and tissue-specific patterns of synthesis of various desmocollin subtypes. Eur J Cell Biol. 1995;66:69-74 pubmed
  49. 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
  50. Khan K, Hardy R, Haq A, Ogunbiyi O, Morton D, Chidgey M. Desmocollin switching in colorectal cancer. Br J Cancer. 2006;95:1367-70 pubmed
    The desmocollins are members of the desmosomal cadherin family of cell-cell adhesion molecules...
  51. Schmitt C, Franke W, Goerdt S, Falkowska Hansen B, Rickelt S, Peitsch W. Homo- and heterotypic cell contacts in malignant melanoma cells and desmoglein 2 as a novel solitary surface glycoprotein. J Invest Dermatol. 2007;127:2191-206 pubmed
    ..Future studies will have to clarify the diagnostic and prognostic significance of these different adhesion protein subtypes. ..
  52. Syrris P, Ward D, Evans A, Asimaki A, Gandjbakhch E, Sen Chowdhry S, et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. Am J Hum Genet. 2006;79:978-84 pubmed
    ..For the first time, we have identified mutations in desmocollin-2 in patients with ARVD/C, a finding that is consistent with the hypothesis that ARVD/C is a disease of the desmosome. ..
  53. Roberts G, Burdett I, Pidsley S, King I, Magee A, Buxton R. Antisense expression of a desmocollin gene in MDCK cells alters desmosome plaque assembly but does not affect desmoglein expression. Eur J Cell Biol. 1998;76:192-203 pubmed
    The desmocollins are one of two types of putative adhesive proteins present in the desmosome type of cell junctions, the other type being the desmogleins; both are members of the cadherin superfamily...