E3 ubiquitin-protein ligase AMFR (AMFR)

E3 ubiquitin-protein ligase that mediates the polyubiquitination of a number of proteins like CD3D, CYP3A4, CFTR and APOB for proteasomal degradation. Component of a VCP/p97- AMFR/gp78 complex that participates in the last step of endoplasmic reticulum-associated degradation (ERAD).

The VCP/p97- AMFR/gp78 complex is included in the sterol-accelerated ERAD degradation of HMGCR through binding to the HMGCR-INSIG complicated at the ER membrane and initiating ubiquitination of HMGCR. The ubiquitinated HMGCR is subsequently released from the ER from the complex into the cytosol for subsequent destruction.