AMFR siRNA – E3 Ubiquitin-Protein Ligase AMFR (Mouse)

AMFR: E3 ubiquitin-protein ligase that mediates the polyubiquitination of a number of proteins such as CD3D, CYP3A4, CFTR and APOB for proteasomal degradation. Component of a VCP/p97- AMFR/gp78 complex that participates in the final step of endoplasmic reticulum-associated degradation (ERAD). The VCP/p97- AMFR/gp78 complex is involved in the sterol-accelerated ERAD degradation of HMGCR through binding to the HMGCR-INSIG complex at the ER membrane and initiating ubiquitination of HMGCR. The ubiquitinated HMGCR is then released from the ER by the complex into the cytosol for subsequent destruction. Also acts as a scaffold protein to assemble a complex that couples ubiquitination, retranslocation and deglycosylation. Mediates tumor invasion and metastasis. Interacts with RNF5. Also forms an ERAD complex containing VCP/p97, NGLY1; PSMC1; SAKS1 AND RAD23B required for coupling retrotranslocation, ubiquitination and deglycosylation. Interacts with DRL1. Interacts (through a region distinct from the RING finger) with UBE2G2/UBC7. Component of the VCP/p97-AMFR/gp78 complex that enhances VCP/p97 binding to polyubiquitinated proteins for their degradation by the endoplasmic reticulum-associated degradation (ERAD) pathway. Interacts (via the VIM) with VCP/p97. Interacts (via its membrane domain) with INSIG1; the interaction initiates the sterol-mediated ubiquitination and degradation of HMGCR by the ERAD pathway. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: Membrane protein, integral; EC 6.3.2.-; Ubiquitin ligase; Membrane protein, multi-pass; Motility/polarity/chemotaxis; Ubiquitin conjugating system; EC 6.3.2.19; Ligase; Receptor, misc.; Endoplasmic reticulum

Cellular Component: endoplasmic reticulum membrane; protein complex; growth cone; membrane; cell soma; endoplasmic reticulum; perinuclear region of cytoplasm; integral to plasma membrane; dendrite; cytoplasm; integral to membrane; integral to endoplasmic reticulum membrane; nucleus

Molecular Function: protein binding; zinc ion binding; coenzyme F420-2 alpha-glutamyl ligase activity; UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D-alanyl-D-alanine ligase activity; metal ion binding; ribosomal S6-glutamic acid ligase activity; ubiquitin-protein ligase activity; nucleotide binding; coenzyme F420-0 gamma-glutamyl ligase activity; receptor activity; ligase activity

Biological Process: ubiquitin-dependent protein catabolic process; ER-associated protein catabolic process; protein polyubiquitination; unfolded protein response; cellular process; protein oligomerization