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Gene Review

PPL  -  periplakin

Homo sapiens

Synonyms: 190 kDa paraneoplastic pemphigus antigen, 195 kDa cornified envelope precursor protein, KIAA0568, Periplakin
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Disease relevance of PPL


High impact information on PPL


Chemical compound and disease context of PPL


Biological context of PPL

  • Interspecific backcross mapping was used to place the murine periplakin gene (Ppl) 0.53 cM distal to marker D16mit32 on the proximal part of murine chromosome 16, close to the locus of mahoganoid (md), a mouse hair mutant [10].
  • Mapping of this gene in human and mouse will allow evaluation of periplakin as a candidate locus for disorders of epithelial fragility, with or without other phenotypes [10].
  • By expressing C-terminal PPL in transfectants, we established a pivotal role for this protein in FcgammaRI ligand binding, endocytosis, and antigen presentation [11].
  • Periplakin is the first protein described to modify the capacity of the melanin-concentrating hormone-1 receptor to initiate signal transduction [12].
  • By transient transfection of COS7 cells and primary human epidermal keratinocytes with deletion mutants of the periplakin C-terminus we mapped sequences required for intermediate filament interaction to two regions of the linker motif that are most highly conserved amongst the plakins [13].

Anatomical context of PPL


Associations of PPL with chemical compounds

  • Periplakin, a novel component of cornified envelopes and desmosomes that belongs to the plakin family and forms complexes with envoplakin [16].
  • Like the NH(2) terminus of desmoplakin, that of periplakin localized to desmosomes; however, in addition, the periplakin NH(2) terminus accumulated at cell surface microvilli in association with cortical actin [6].
  • Coexpression of the melanin-concentrating hormone-1 receptor with periplakin in human embryonic kidney 293 cells did not prevent agonist-mediated internalization of the receptor but did interfere with binding of (35)S-labeled guanosine 5'-3-O-(thio)triphosphate ([(35)S]GTPgammaS) to the G protein Galpha(o1) and the elevation of [Ca(2+)](i) [12].
  • These findings raise the possibility that envoplakin and periplakin bind to the plasma membrane upon elevation of intracellular [Ca(2+)] in differentiating keratinocytes, where they serve as a scaffold for cornified cell envelope assembly [15].
  • Biphasic cerebral uptake of tyrosine was observed during and immediately after PBZ and PPL infusion [17].

Physical interactions of PPL

  • Analysis of interactions between the C-terminal tail of the MOP-1 and MOP-1A variants of the human mu-opioid receptor with proteins derived from a human brain cDNA library resulted in identification of the actin and intermediate filament-binding protein periplakin [18].
  • Interactions between G-protein-coupled receptors and periplakin: a selective means to regulate G-protein activation [19].

Other interactions of PPL


Analytical, diagnostic and therapeutic context of PPL


  1. Molecular analysis of Spanish patients with AMP deaminase deficiency. Rubio, J.C., Martín, M.A., Del Hoyo, P., Bautista, J., Campos, Y., Segura, D., Navarro, C., Ricoy, J.R., Cabello, A., Arenas, J. Muscle Nerve (2000) [Pubmed]
  2. Envoplakin and periplakin are the paraneoplastic pemphigus antigens. Kiyokawa, C. The Kurume medical journal. (1999) [Pubmed]
  3. Sensitivity and specificity of clinical, histologic, and immunologic features in the diagnosis of paraneoplastic pemphigus. Joly, P., Richard, C., Gilbert, D., Courville, P., Chosidow, O., Roujeau, J.C., Beylot-Barry, M., D'incan, M., Martel, P., Lauret, P., Tron, F. J. Am. Acad. Dermatol. (2000) [Pubmed]
  4. Proteomic analysis of primary esophageal squamous cell carcinoma reveals downregulation of a cell adhesion protein, periplakin. Nishimori, T., Tomonaga, T., Matsushita, K., Oh-Ishi, M., Kodera, Y., Maeda, T., Nomura, F., Matsubara, H., Shimada, H., Ochiai, T. Proteomics (2006) [Pubmed]
  5. Kazrin, a novel periplakin-interacting protein associated with desmosomes and the keratinocyte plasma membrane. Groot, K.R., Sevilla, L.M., Nishi, K., DiColandrea, T., Watt, F.M. J. Cell Biol. (2004) [Pubmed]
  6. Subcellular distribution of envoplakin and periplakin: insights into their role as precursors of the epidermal cornified envelope. DiColandrea, T., Karashima, T., Määttä, A., Watt, F.M. J. Cell Biol. (2000) [Pubmed]
  7. The members of the plakin family of proteins recognized by paraneoplastic pemphigus antibodies include periplakin. Mahoney, M.G., Aho, S., Uitto, J., Stanley, J.R. J. Invest. Dermatol. (1998) [Pubmed]
  8. Carboplatin plus ifosfamide as salvage treatment of epithelial ovarian cancer: a pilot study. Lorusso, V., Catino, A., Leone, B., Rabinovich, M., Gargano, G., Paradiso, A., De Lena, M. J. Clin. Oncol. (1993) [Pubmed]
  9. Clinical trial of Ro 6-0787, a monovalent specific hapten inhibitor of penicillin allergy. De Weck, A.L., Jeunet, F., Schulz, K.H., Louis, P., Girard, J.P., Grilliat, J.P., Moneret-Vautrin, D., Storck, H., WUthrich, B., Spengler, H., Juhlin, L., Scheiffarth, F., Warnatz, H., Wortmann, F., Virgaay SRN, Schweiz, n.u.l.l. Zeitschrift für Immunitätsforschung, experimentelle und klinische Immunologie. (1975) [Pubmed]
  10. cDNA cloning, mRNA expression, and chromosomal mapping of human and mouse periplakin genes. Aho, S., McLean, W.H., Li, K., Uitto, J. Genomics (1998) [Pubmed]
  11. Direct interaction between FcgammaRI (CD64) and periplakin controls receptor endocytosis and ligand binding capacity. Beekman, J.M., Bakema, J.E., van de Winkel, J.G., Leusen, J.H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  12. Periplakin interferes with G protein activation by the melanin-concentrating hormone receptor-1 by binding to the proximal segment of the receptor C-terminal tail. Murdoch, H., Feng, G.J., Bächner, D., Ormiston, L., White, J.H., Richter, D., Milligan, G. J. Biol. Chem. (2005) [Pubmed]
  13. Interaction of periplakin and envoplakin with intermediate filaments. Karashima, T., Watt, F.M. J. Cell. Sci. (2002) [Pubmed]
  14. Unique role for the periplakin tail in intermediate filament association: specific binding to keratin 8 and vimentin. Kazerounian, S., Uitto, J., Aho, S. Exp. Dermatol. (2002) [Pubmed]
  15. Co-assembly of envoplakin and periplakin into oligomers and Ca(2+)-dependent vesicle binding: implications for cornified cell envelope formation in stratified squamous epithelia. Kalinin, A.E., Idler, W.W., Marekov, L.N., McPhie, P., Bowers, B., Steinert, P.M., Steven, A.C. J. Biol. Chem. (2004) [Pubmed]
  16. Periplakin, a novel component of cornified envelopes and desmosomes that belongs to the plakin family and forms complexes with envoplakin. Ruhrberg, C., Hajibagheri, M.A., Parry, D.A., Watt, F.M. J. Cell Biol. (1997) [Pubmed]
  17. Influence of adrenergic receptor blockade on circulatory and metabolic effects of disordered neurotransmitter function in stroke patients. Meyer, J.S., Miyakawa, Y., Welch, K.M., Itoh, Y., Ishihara, N., Chabi, E., Nell, J., Bartosh, K., Ericsson, A.D. Stroke (1976) [Pubmed]
  18. Selective interactions between helix VIII of the human mu-opioid receptors and the C terminus of periplakin disrupt G protein activation. Feng, G.J., Kellett, E., Scorer, C.A., Wilde, J., White, J.H., Milligan, G. J. Biol. Chem. (2003) [Pubmed]
  19. Interactions between G-protein-coupled receptors and periplakin: a selective means to regulate G-protein activation. Milligan, G., Murdoch, H., Kellett, E., White, J.H., Feng, G.J. Biochem. Soc. Trans. (2004) [Pubmed]
  20. Plakin proteins are coordinately cleaved during apoptosis but preferentially through the action of different caspases. Aho, S. Exp. Dermatol. (2004) [Pubmed]
  21. Characterization of periphilin, a widespread, highly insoluble nuclear protein and potential constituent of the keratinocyte cornified envelope. Kazerounian, S., Aho, S. J. Biol. Chem. (2003) [Pubmed]
  22. Paraneoplastic pemphigus resembling linear IgA bullous dermatosis. Lee, J.S., Ng, P.P., Tao, M., Lim, W.T. International journal of dermatology. (2006) [Pubmed]
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