ADP-ribosylation factor-like protein 6-interacting protein 1, Reticulophagy regulator 3, and similar proteins
This family contains ADP-ribosylation factor-like 6 binding factor 1 (Arl6IP1 or Arl6ip-1) and the N-terminal reticulon-homology domain (RHD) of Reticulophagy regulators 1-3. Arl6IP1 is an endoplasmic reticulum (ER) protein that has an important role in cell conduction and material transport. Arl6IP1, a tetraspan membrane protein, is an anti-apoptotic protein specific to multicellular organisms, and is a potential player in shaping the ER tubules in mammalian cells. In Drosophila, knockdown of the Arl6IP1 gene leads to progressive motor deficit. An Arl6IP1 variant has also been associated with hereditary spastic paraplegia (HSP), motor and sensory polyneuropathy, and acromutilation. 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. Arl6IP1 shows some sequence similarity to the RHD of reticulophagy regulators, which may function in inducing membrane curvature.