N-terminal reticulon-homology domain of Reticulophagy regulators and similar proteins
This subfamily includes Reticulophagy regulators 1-3. Reticulophagy regulator 1 (RETREG1/FAM134B) is an endoplasmic reticulum (ER)-anchored autophagy receptor that regulates the size and shape of the ER. It regulates turnover of the ER by selective phagocytosis, mediating ER delivery into lysosomes through sequestration into autophagosomes. It promotes membrane remodeling and ER scission through its membrane bending activity, and targets the fragments into autophagosomes by interacting with ATG8 family modifier proteins such as MAP1LC3A, MAP1LC3B, GABARAP, GABARAPL1 and GABARAPL2. RETREG2/FAM134A and RETREG3/FAM134C has been shown to interact with ATG8 family modifier proteins MAP1LC3A, MAP1LC3B, GABARAP, and GABARAPL1. Members of this subfamily contain an N-terminal reticulon-homology domain (RHD) that shows sequence similarity to ADP-ribosylation factor-like 6 binding factor 1 (Arl6IP1 or Arl6ip-1), an ER protein that has an important role in cell conduction and material transport. The RHD may function in inducing membrane curvature.