AMFR Protein, Human (Cell-Free, His)

AMFR, an E3 ubiquitin-protein ligase, orchestrates the polyubiquitination of target proteins, including CD3D, CYP3A4, CFTR, INSIG1, SOAT2/ACAT2, and APOB, marking them for proteasomal degradation. As a component of the VCP/p97-AMFR/gp78 complex, it plays a pivotal role in the endoplasmic reticulum-associated degradation (ERAD) process, facilitating the degradation of HMGCR and INSIG1 during sterol-accelerated ERAD. Through interaction with AUP1, AMFR engages with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase RNF139, contributing to sterol-induced HMGCR ubiquitination and subsequent degradation. Furthermore, AMFR participates in ubiquitination on cysteine residues, targeting SOAT2/ACAT2 and INSIG2 for degradation under specific cellular conditions. Acting as a scaffold protein, AMFR assembles a complex that couples ubiquitination, retranslocation, and deglycosylation. It serves as a receptor for GPI/autocrine motility factor, promoting tumor invasion and metastasis. Moreover, in collaboration with LMBR1L and UBAC2, AMFR negatively regulates the canonical Wnt signaling pathway by facilitating the ubiquitin-mediated degradation of CTNNB1 and Wnt receptors FZD6 and LRP6, and it modulates NF-kappa-B and MAPK signaling pathways by mediating 'Lys-27'-linked polyubiquitination of TAB3, leading to TAK1/MAP3K7 activation.