FNDC5
Description
The FNDC5 (fibronectin type III domain containing 5) is a protein-coding gene located on chromosome 1.
FNDC5, a gene encoding Fibronectin type III domain-containing protein 5, produces a type I transmembrane glycoprotein. Irisin, named after the Greek messenger goddess, is a cleaved version of FNDC5. The protein comprises a short cytoplasmic domain, a transmembrane segment, and an ectodomain containing a fibronectin type III (FNIII) domain. FNDC5 was discovered in 2002 through searches for fibronectin type III domains and peroxisomal proteins. The ectodomain was proposed to be cleaved into irisin, a soluble peptide hormone. Irisin was suggested to be secreted from muscle in response to exercise and potentially mediate beneficial effects of exercise, including weight loss and diabetes prevention. However, these findings have been debated. A 2021 review highlighted new roles for irisin in brain function and bone remodeling but criticized studies using commercial antibody assays to measure irisin levels. The review also questioned how an exercise hormone could have evolved. Subsequent research using FNDC5 knock-out mice and artificial elevation of circulating irisin levels demonstrated that irisin confers cognitive benefits associated with physical exercise and can act as an exercise mimetic in mice.
FNDC5 is also known as FRCP2, irisin.
