EPPK1

Description

The EPPK1 (epiplakin 1) is a protein-coding gene located on chromosome 8.

Epiplakin is a protein encoded by the EPPK1 gene in humans. It belongs to the plakin protein family and is found in the human epidermis. Epiplakin consists of 13 domains similar to the B domain found in desmoplakin, a protein involved in cell-to-cell junctions. These domains share 46 to 70% homology with the B domain of desmoplakin. Epiplakin was first identified as an autoantigen in a person with a rare autoimmune skin disease. It contains 5065 amino acid residues and has a molecular weight of approximately 552 kDa. The EPPK1 gene is unique because its entire 15 kbp coding region is encoded by a single exon, lacking introns. Epiplakin binds to keratin filaments and may inhibit their growth. This is suggested by the observation that keratin-bound epiplakin is primarily located at branch points and endpoints of keratin filaments. Blocking epiplakin expression in cultured corneal epithelial cells using siRNA is associated with faster wound closure and increased migration of corneal cells.

Epiplakin is a cytoskeletal linker protein that connects to intermediate filaments and controls their reorganization in response to stress. It plays a role in cellular motility by slowing down keratinocyte migration and proliferation and accelerating keratin bundling in proliferating keratinocytes, thus contributing to tissue architecture. However, in wound healing in corneal epithelium, it also positively regulates cell differentiation and proliferation and negatively regulates migration, thereby controlling corneal epithelium morphogenesis and integrity. Epiplakin protects keratin filaments against disruption during cellular stress and plays a protective role by chaperoning disease-induced intermediate filament reorganization during liver and pancreas injuries. It interacts with keratin filaments, preferentially with assembled filaments rather than keratin monomers. Epiplakin interacts with KRT5, KRT14, and KRT5/KRT14 heterotetramer, KRT8, KRT18, and KRT8/KRT18 heterotetramer, and KRT1, VIM, and DES. Its interaction with KRT1 is stronger than with VIM or DES, and its interaction depends on the higher-order structure of the intermediate filament.

EPPK1 is also known as EPIPL, EPIPL1.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing