Ferlins

Article summary

Ferlins are an ancient protein family involved in vesicle fusion and membrane trafficking. Ferlins are distinguished by their multiple tandem C2 domains, and sometimes a FerA and a DysF domain. Mutations in ferlins can cause human diseases such as muscular dystrophy and deafness. Abnormalities in expression of myoferlin, a human ferlin protein, is also directly associated with higher mortality rate and tumor recurrence in several types of cancer, including pancreatic, colorectal, breast, cervical, stomach, ovarian, cervical, thyroid, endometrial, and oropharyngeal squamous cell carcinoma. In other animals, ferlin mutations can cause infertility. Ferlins are type II transmembrane proteins (N-terminus on the cytoplasmic side of the membrane) and contain five to seven C2 domains linked in tandem and have a single-pass transmembrane domain located at the C-terminus. The C2 domains are denoted in order from amino-terminus to carboxyl-terminus as C2A to C2G. C2 domains are essentially calcium and phospholipid binding domains, evolved for cell membrane interactions. In fact, many proteins involved in signal transduction, membrane trafficking, and membrane fusion employ C2 domains to target the cell membrane. However, ferlins are unique for containing more C2 domains than any other proteins (between five and seven).…

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