Epiplakin Explained

Epiplakin is a protein that in humans is encoded by the EPPK1 gene.^{[1] [2] [3]} It belongs to the family of plakin proteins and is found in the human epidermis. It consists of 13 domains which are all similar to the B domain located at the C terminus of the human epidermal and cardiac muscle protein desmoplakin.^[1] The domains in epiplakin range from 46 to 70% in their homology to this B domain in desmoplakin.^[4] It was first identified as an autoantigen in a person who suffers from a rare autoimmune skin disease. Epiplakin was sequenced to have a total of 5065 amino acid residues and based on its amino acid composition it has a molecular weight of about 552 kDa. The EPPK1 gene is notable for a lack of introns over its coding region - its entire 15 kbp coding region is encoded by a single exon.^[5]

Epiplakin has been found to bind to keratin filaments and may contribute to inhibiting the growth of the filaments. This is suspected due to keratin bound epiplakin being found primarily at branch-points and end-points of the keratin filaments.^[6] Blocking the expression of epiplakin in cultured corneal epithelial cells via siRNA has been associated with faster wound closure and faster migration of corneal cells.^[7] This may be due to the loss of epiplakin leading to a modification of the cytoskeleton in epithelial cells.

Further reading

• Fujiwara S, Kohno K, Iwamatsu A, Naito I, Shinkai H . Identification of a 450-kDa human epidermal autoantigen as a new member of the plectin family . The Journal of Investigative Dermatology . 106 . 5 . 1125–30 . May 1996 . 8618051 . 10.1111/1523-1747.ep12340171 . free .
• Blagoev B, Kratchmarova I, Ong SE, Nielsen M, Foster LJ, Mann M . A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling . Nature Biotechnology . 21 . 3 . 315–8 . March 2003 . 12577067 . 10.1038/nbt790 . 26838266 .
• Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides . Nature Biotechnology . 21 . 5 . 566–9 . May 2003 . 12665801 . 10.1038/nbt810 . 23783563 .
• Spazierer D, Fuchs P, Pröll V, Janda L, Oehler S, Fischer I, Hauptmann R, Wiche G . 6 . Epiplakin gene analysis in mouse reveals a single exon encoding a 725-kDa protein with expression restricted to epithelial tissues . The Journal of Biological Chemistry . 278 . 34 . 31657–66 . August 2003 . 12791695 . 10.1074/jbc.M303055200 . free .
• Takeo N, Wang W, Matsuo N, Sumiyoshi H, Yoshioka H, Fujiwara S . Structure and heterogeneity of the human gene for epiplakin (EPPK1) . The Journal of Investigative Dermatology . 121 . 5 . 1224–6 . November 2003 . 14708632 . 10.1046/j.1523-1747.2003.12550_5.x . free .
• Kim JE, Tannenbaum SR, White FM . Global phosphoproteome of HT-29 human colon adenocarcinoma cells . Journal of Proteome Research . 4 . 4 . 1339–46 . 2005 . 16083285 . 10.1021/pr050048h .
• Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R . Phosphoproteome analysis of the human mitotic spindle . Proceedings of the National Academy of Sciences of the United States of America . 103 . 14 . 5391–6 . April 2006 . 16565220 . 1459365 . 10.1073/pnas.0507066103 . 2006PNAS..103.5391N . free .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–48 . November 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . 6 . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .

Notes and References

1. Fujiwara S, Takeo N, Otani Y, Parry DA, Kunimatsu M, Lu R, Sasaki M, Matsuo N, Khaleduzzaman M, Yoshioka H . 6 . Epiplakin, a novel member of the Plakin family originally identified as a 450-kDa human epidermal autoantigen. Structure and tissue localization . The Journal of Biological Chemistry . 276 . 16 . 13340–7 . April 2001 . 11278896 . 10.1074/jbc.M011386200 . free .
2. Jang SI, Kalinin A, Takahashi K, Marekov LN, Steinert PM . Characterization of human epiplakin: RNAi-mediated epiplakin depletion leads to the disruption of keratin and vimentin IF networks . Journal of Cell Science . 118 . Pt 4 . 781–93 . February 2005 . 15671067 . 10.1242/jcs.01647 . 38183338 .
3. Web site: Entrez Gene: EPPK1 epiplakin 1.
4. Takeo N, Wang W, Matsuo N, Sumiyoshi H, Yoshioka H, Fujiwara S . Structure and heterogeneity of the human gene for epiplakin (EPPK1) . The Journal of Investigative Dermatology . 121 . 5 . 1224–6 . November 2003 . 14708632 . 10.1046/j.1523-1747.2003.12550_5.x . free .
5. Book: Stewart., Scherer. A short guide to the human genome. 2008. Cold Spring Harbor Laboratory Press. 978-0-87969-791-4. 301791139.
6. Wang W, Sumiyoshi H, Yoshioka H, Fujiwara S . Interactions between epiplakin and intermediate filaments . The Journal of Dermatology . 33 . 8 . 518–27 . August 2006 . 16923132 . 10.1111/j.1346-8138.2006.00127.x . 25372989 .
7. Kokado M, Okada Y, Miyamoto T, Yamanaka O, Saika S . Effects of epiplakin-knockdown in cultured corneal epithelial cells . BMC Research Notes . 9 . 1 . 278 . May 2016 . 27206504 . 4873999 . 10.1186/s13104-016-2082-7 . free .