Hemojuvelin

Hemojuvelin (HJV/RGMc/HFE2) is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosis in humans, a severe form of hemochromatosis. In humans, the hemojuvelin protein is encoded by the HFE2 gene. HJV is also called RGMc, a member of a three gene family (in vertebrates) called the repulsive guidance molecules. Both RGMa and RGMb are found in the nervous system while RGMc is found in skeletal muscle and the liver.

Function

For many years the signal transduction pathways that regulate systemic iron homeostasis have been unknown. However it has been demonstrated that hemojuvelin interacts with bone morphogenetic protein (BMP), possibly as a co-receptor, and may signal via the SMAD pathway to regulate hepcidin expression. Associations with BMP2 and BMP4 have been described.

Mouse HJV knock-out models confirmed that HJV is the gene responsible for juvenile hemochromatosis. Hepcidin levels in the liver are dramatically depressed in these knockout animals.