Protein: E3 ubiquitin-protein ligase AMFR (EC 2.3.2.36) (Autocrine motility factor receptor) (AMF receptor) (RING-type E3 ubiquitin transferase AMFR) (Q9R049)
Organism: Mus musculus (Mouse)
Function: E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins, such as CD3D, CYP3A4, CFTR, INSIG1, SOAT2/ACAT2 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-INSIG1 complex at the ER membrane. In addition, interaction of AMFR with AUP1 facilitates interaction of AMFR with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase RNF139, leading to sterol-induced HMGCR ubiquitination (By similarity). The ubiquitinated HMGCR is then released from the ER by the complex into the cytosol for subsequent destruction (By similarity). In addition to ubiquitination on lysine residues, catalyzes ubiquitination on cysteine residues: together with INSIG1, mediates polyubiquitination of SOAT2/ACAT2 at 'Cys-277', leading to its degradation when the lipid levels are low (By similarity). Catalyzes ubiquitination and subsequent degradation of INSIG1 when cells are depleted of sterols (By similarity). Mediates polyubiquitination of INSIG2 at 'Cys-215' in some tissues, leading to its degradation (By similarity). Also regulates ERAD through the ubiquitination of UBL4A a component of the BAG6/BAT3 complex (By similarity). Also acts as a scaffold protein to assemble a complex that couples ubiquitination, retranslocation and deglycosylation (By similarity). Mediates tumor invasion and metastasis as a receptor for the GPI/autocrine motility factor. In association with LMBR1L and UBAC2, negatively regulates the canonical Wnt signaling pathway in the lymphocytes by promoting the ubiquitin-mediated degradation of CTNNB1 and Wnt receptors FZD6 and LRP6.
Subcellular location: Endoplasmic reticulum membrane {ECO:0000269|PubMed:16987818}; Multi-pass membrane protein {ECO:0000255}. Note=Palmitoylation promotes localization to the peripheral endoplasmic reticulum. {ECO:0000250|UniProtKB:Q9UKV5}.
Interaction partners:
- Ubiquitin-conjugating enzyme E2 G2
- Transitional endoplasmic reticulum ATPase
- Insulin-induced gene 1 protein
- Derlin-1
- Protein sel-1 homolog 1
- Peptide-N
- FAS-associated factor 2
- Derlin-2
- UV excision repair protein RAD23 homolog B
- Erlin-2
Sequence:
MPLLFLERFPWPSLRTYTGLSGLALLGTIVSAYRALSQPEDGSGEPEPLTAPLQPEALAPARLTAGGPRARDVAQYLLSDSLFVWVLVNTACCVLMLVAKLIQCIVFGPLRVSERQHLKDKFWNFIFYKFIFIFGVLNVQTVEEVVMWCLWFAGLVFLHLMVQLCKDRFEYLSFSPTTPMSSHGRVLSLLIAMLLSCCGLAVVCCVTGYTHGMHTLAFMAAESLLVTVRTAHVILRYVIHLWDLNHEGTWEGKGTYVYYTDFVMELALLSLDLMHHIHMLLFGNIWLSMASLVIFMQLRYLFHEVQRRIRRHKNYLRVVGNMEARFAVATPEELAVNNDDCAICWDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSLNIADGSRAREDHQGENLDENLVPVAAAEGRPRLNQHNHFFHFDGSRIASWLPSFSVEVMHTTNILGITQASNSQLNAMAHQIQEMFPQVPYHLVLQDLQMTRSVEITTDNILEGRIQVPFPTQRSDSLRPALNSPVERPSPDLEEGEASVQTERVPLDLSPRLEETLDFSEVELEPIEVEDFEARGSRFSKSADERQRMLVQRKDDLLQQARKRFLNKSSEDDGASERLLPSEGTSSDPVTLRRRMLAAAAERRLQRQRTT