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Symbol AMFR contributors: mct/npt - updated : 30-12-2015
HGNC name autocrine motility factor receptor
HGNC id 463
Type ubiquitous
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivepharynx   highly
Lymphoid/Immunelymph node   highly
Nervousbrain   highly
cell lineage
cell lines
  • a seven transmembrane domain
  • a leucine-zipper motif
  • two important domains, RING finger (a RING-H2 motif) and CUE domain showing preferential binding to the ubiquitin chain compared to monoubiquitin
  • G2BR domain is involved in ubiquitin chain synthesis by binding to the donor UBE2G2~UB and promoting ubiquitin transfer from the E2 in cis
  • conjugated GlycoP
    CATEGORY signaling , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • localizes to mitochondria-associated ER and targets the mitofusin (MFN1 and MFN2) mitochondrial fusion proteins for degradation
  • basic FUNCTION
  • RING finger-dependent ubiquitin protein ligase (E3) of the endoplasmic reticulum (ER) (Fang 2001)
  • tumor motility-stimulating protein secreted by tumor cells
  • required for sterol-regulated ubiquitination of reductase
  • membrane-anchored ubiquitin ligase, promoting degradation of misfolded endoplasmic reticulum (ER) proteins and sterol-regulated degradation of HMG-CoA reductase (Cao 2007)
  • participates in ERAD of the CFTR mutant CFTRDeltaF508, by specifically promoting ubiquitylation of CFTRDeltaF508 (Morito 2008)
  • E3 ubiquitin ligase involved in ER-associated degradation (ERAD)(Ying 2009)
  • facilitates the degradation of two ER-associated proteins SOD1 and ataxin-3 by ERAD pathway and suppresses their aggregation in the ER (Ying 2009)
  • AMFR and RNF139 are implicated in the sterol-regulated degradation of HMG-CoA reductase and INSIG1 through ER-associated degradation (ERAD)
  • regulates critical proteins via the ubiquitin-proteasome system to maintain cellular homeostasis, including its CUE domain, which is essential for function
  • INSIG-associated ubiquitin ligases AMFR and RNF139, is obligatory for extraction of reductase from lipid droplet-associated ER membranes into the cytosol for proteasome-mediated, ER-associated degradation (ERAD)
  • novel role for the ER-associated AMFR ubiquitin ligase and the MFN1 mitochondrial fusion factor in mitophagy
  • regulates mitochondrial antiviral signaling (MAVS) signaling through two parallel pathways: one pathway requires its E3 ubiquitin ligase and ERAD activity to directly degrade MAVS, whereas the other pathway requires its RING domain and occurs via a direct association between this region and MAVS
  • ubiquitin ligase that plays a vital role in endoplasmic reticulum (ER)-associated degradation (ERAD)
  • elongates of polyubiquitin chains from the distal end through the cooperation of its G2BR and CUE domains
  • AMFR and INSIG1, an E3 ubiquitin ligase complex, then catalyzed the K27-linked polyubiquitination of CISD2
  • essential role of the ER proteins AMFR and INSIG1 in innate immunity, revealing an important missing link in the CISD2 signaling pathway
  • AMFR is the cell surface receptor for autocrine motility factor (GPI), which prevents AMFR-dependent mitofusin degradation
  • GPI is a multifunctional protein that stimulates cell growth and migration, together with its receptor autocrine motility factor receptor (AMFR)
  • CELLULAR PROCESS cell communication
    a component
    small molecule
  • binds to INSIG1 (membrane-anchored ubiquitin ligase, associating with INSIG1 and coupling sterol-regulated ubiquitination to degradation of HMG CoA reductase)
  • cooperates with RNF5 in endoplasmic reticulum-associated degradation of CFTRDeltaF508 (Morito 2008)
  • interacting with UFD1L directly (interacts with AMFR and functions as a cofactor) (Cao 2007)
  • interacts with both SOD1 and ataxin-3 (AMFR functions in the regulation of SOD1 and ataxin-3 to target them for ERAD) (Ying 2009)
  • role for CD82 in promotion of cell proliferation and mammary gland hyperplasia by the AMFR ubiquitin ligase
  • ER membrane proteins, ERLIN2 and TMUB1, are associated proteins of mammalian AMFR, a membrane-bound ubiquitin ligase that mediates sterol-accelerated ERAD of the cholesterol biosynthetic enzyme HMGCR
  • sterol-induced ubiquitination and proteasomal degradation of reductase is dictated by the complex interplay of at least four proteins: INSIG1, INSIG2, AMFR, and RNF139
  • palmitoylation of RING finger cysteines therefore regulates AMFR distribution to the peripheral ER
  • ubiquitin ligase (E3) AMFR has been implicated in the sterol-regulated degradation of HMGCR and INSIG1 through ER-associated degradation (ERAD)
  • lipid droplet-associated, that is one of several proteins that copurify with AMFR, and involved in ubiquitination of HMGCR
  • ERAD E3 AMFR can ubiquitinate not only ERAD substrates, but also the machinery protein UBL4A, a key component of the BAG6 chaperone complex
  • USP13 is a AMFR-associated DUB that eliminates ubiquitin conjugates from UBL4A to maintain the functionality of BAG6
  • is critical for unglycosylated PRNP ubiquitylation and degradation
  • polyubiquitylation of GPI requires cooperative interaction between AMFR and the ubiquitin ligase TRIM25
  • DGAT2 is regulated by AMFR-associated ERAD at the post-translational level
  • regulation of close smooth ER-mitochondria contacts by MFN1 and of rough ER-mitochondria contacts by GPI-sensitive AMFR-mediated degradation of MFN2 define new mechanisms that regulate ER-mitochondria interactions
  • cell & other
    Other phosphorylated by the autocrine motility factor which acts to stimulate migratin of fibrosarcoma cells
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in gastric carcinoma with poor prognosis
    tumoral     --over  
    in many types of cancers including lung, stomach, colon, liver and skin cancer
    tumoral     --over  
    in prostate cancers especially early stage tumors
    Variant & Polymorphism
    Candidate gene
  • levels of autocrine motility factor receptor (AMFR) were concordantly lower in plasma of female osteoporosis patients
  • could be a putative biomarker for prostate cancer diagnosis
  • Therapy target
    may represent a potential target for the treatment of acute monocytic leukemia