Mesencephalic astrocyte-derived neurotrophic factor (MANF), Arginine-rich, mutated in early-stage tumors (ARMET), or arginine-rich protein (ARP) is a protein that in humans is encoded by the MANF housekeeping gene.
This gene encodes a highly conserved protein whose function is known. The protein was initially thought to be longer at the N-terminus and to contain an arginine-rich region but transcribed evidence indicates a smaller open reading frame that does not encode the arginine tract. The presence of a specific mutation changing the previously numbered codon 50 from ATG to AGG, or deletion of that codon, has been reported in a variety of solid tumors. With the protein size correction, this codon is now identified as the initiation codon.
MANF has cytoprotective effects in neurons and pancreatic β cells, both in vitro (cell culture) and in vivo (animal models of neurodegeneration and diabetes). Specifically, it protects dopamine neurons from endoplasmic reticulum (ER) stress-induced death. It exerts this action by binding to ERN1, the unfolded protein response (UPR) sensor in the ER, which results in the attenuation of UPR.
