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N-terminal reticulon-homology domain of Reticulophagy regulator 1 Reticulophagy regulator 1 (RETR1 or RETREG1), also called reticulophagy receptor 1 or FAM134B (family with sequence similarity 134, member B), 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. Loss of function of FAM134B is associated with diseases and cancer, including hereditary sensory and autonomic neuropathy type IIB (HSAN IIB), colorectal adenocarcinoma, and oesophageal squamous cell carcinoma, and other progressive neuronal degenerative diseases. FAM134B is also implicated in the suppression of viral replication during Ebola, Dengue, Zika, and West Nile viral infections. RETREG1/FAM134B contains 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. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",