Transmembrane channel-like protein 8 (TMC8), also known as Epidermodysplasia verruciformis protein 2 (EVER2), is a 726 amino acid member of the TMC family of proteins. Localized to the endoplasmic reticulum membrane, TMC8 is thought to form a transmembrane channel-like protein with eight predicted transmembrane domains and three leucine zipper motifs. Mutations in the genes encoding TMC8 and TMC6, another member of the TMC family, have been shown to cause epidermodysplasia verruciformis (EV), an autosomal recessive dermatosis characterized by abnormal susceptibility to human papillomaviruses (HPVs) and a high rate of progression to squamous cell carcinoma on sun-exposed skin. Infection by HPVs lead to persistent wart-like or macular lesions. TMC8 is expressed in placenta, prostate and testis, and three named isoforms exist as a result of alternative splicing events.
Function:
Epidermodysplasia verruciformis (EV) is an autosomal recessive genodermatosis associated with a high risk of skin cancers resulting from a high susceptibility to infection by specific human papillomaviruses. Mutations in two homologous genes EVER1 and EVER2 cause the majority of EV cases. These two proteins form a complex and interact with the zinc transporter ZnT-1 in the endoplasmic reticulum. Cells lacking EVER2 accumulated higher levels of zinc in the nucleolus and nucleus compare to those cells with and intact EVER2 gene, indicating that one role of EVER2 is to regulate the intracellular distribution of zinc. At least two isoforms of EVER2 are known to exist.
Subcellular Location:
Endoplasmic reticulum membrane; Multi pass membrane protein.
Tissue Specificity:
Expressed in placenta, prostate and testis.
DISEASE:
Defects in TMC8 are a cause of epidermodysplasia verruciformis (EV) [MIM:221280]. It is a rare autosomal recessive genodermatosis associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses. Infection leads to persistent wart-like or macular lesions.
Similarity:
Belongs to the TMC family.
SWISS:
Q8IU68
Gene ID:
147138
Database links:
Entrez Gene: 147138 Human
Entrez Gene: 217356 Mouse
Omim: 605829 Human
SwissProt: Q8IU68 Human
SwissProt: Q7TN58 Mouse
Unigene: 592102 Human
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