8.A.195.  The Erlin1/2 Complex (Erlin) Family 

The ERLIN1/ERLIN2 complex mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs). Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway. The erlin complex binds cholesterol and may promote ER retention of the SCAP-SREBF complex (Huber et al. 2013). It is required early in hepatitis C virus (HCV) infection to initiate RNA replication, and later in the infection to support infectious virus production (Whitten-Bauer et al. 2019). The binding of the erlin1/2 complex to the third intralumenal loop of the inositol triP receptor 1 (IP3R1; TC# 1.A.3.2.6) triggers its ubiquitin-proteasomal degradation (Gao et al. 2022). The Erlin1/2 complex is involved as part of the SV40 ER membrane penitration complex (TC# 1.P.1.1.1).