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FLASH GENE
Symbol AMFR contributors: mct/npt - updated : 30-12-2015
HGNC name autocrine motility factor receptor
HGNC id 463
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivepharynx   highly
Lymphoid/Immunelymph node   highly
Nervousbrain   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • 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
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY signaling , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • 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
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
    REGULATION
    Other phosphorylated by the autocrine motility factor which acts to stimulate migratin of fibrosarcoma cells
    ASSOCIATED DISORDERS
    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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • 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
    SystemTypeDisorderPubmed
    cancerhemopathy 
    may represent a potential target for the treatment of acute monocytic leukemia
    ANIMAL & CELL MODELS