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 as a receptor for the GPI/autocrine motility factor.
Specificity
Natural and recombinant Human E3 ubiquitin-protein ligase AMFR
Subcellular Location
Endoplasmic reticulum membrane Multi-pass membrane protein
Interacts with RNF5. Also forms an ERAD complex containing VCP/p97, NGLY1; PSMC1; SAKS1 AND RAD23B required for coupling retrotranslocation, ubiquitination and deglycosylation (By similarity). 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.
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: FUNCTION AS A UBIQUITIN LIGASE;SUBCELLULAR LOCATION;INTERACTION WITH UBE2G2
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: INTERACTION WITH INSIG1 AND VCP;FUNCTION;MUTAGENESIS OF CYS-356
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-516;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 622-640 IN COMPLEX WITH VCP;VIM MOTIF