E3 ubiquitin-protein ligase AMFR (AMFR)

E3 ubiquitin-protein ligase AMFR (commonly called autocrine motility factor receptor, AMFR, or gp78) is a multi-pass transmembrane glycoprotein that serves dual functions as a cell-surface receptor for autocrine motility factor (AMF; also known as glucose-6-phosphate isomerase) and as a RING-type E3 ubiquitin ligase primarily involved in ER-associated degradation (ERAD) of misfolded proteins[2][3][5][6][7]. At the cell surface, AMFR mediates signaling upon binding AMF, activating pathways that regulate cytoskeletal remodeling, cell motility, proliferation, apoptosis resistance, and metastasis—particularly relevant in malignancies such as breast, prostate, and musculoskeletal (bone and soft tissue) cancers[1][3][7]. Intracellularly, AMFR/gp78 resides in the endoplasmic reticulum membrane, where it ubiquitinates a variety of protein substrates, coordinating their degradation through the proteasomal pathway to maintain protein homeostasis[2][6]. The receptor is part of the RING finger E3 ligase family, containing characteristic domains (RING-type zinc finger, CUE domain, VCP/p97-interacting motif) essential for ligase activity and interaction with chaperones and other ERAD components[3]. AMFR expression is often upregulated in metastatic or aggressive tumors, and both AMF and AMFR are considered _moonlighting_ proteins that contribute to the altered metabolism and invasive phenotype of cancer cells[2][3][7]. Currently, AMFR is regarded as a promising therapeutic target for anti-metastatic strategies, though direct pharmacological inhibitors have not yet reached clinical application[3][7].

Other names

Autocrine motility factor receptorgp78RNF45AMF receptorRING finger protein 45SPG89RING-type E3 ubiquitin transferase AMFR

Proposed mechanisms for investigational inhibitors: inhibition of AMF-AMFR interaction, E3 ligase function blockade, suppression of signaling related to motility/metastasis[3].