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IID00226
 UniprotQ9UKV5
ProteinE3 ubiquitin-protein ligase AMFR
GeneAMFR
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
 Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
643
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 313-393 Monomer :
 Evidence NMR 2lxh C Reference
       Region 2lxh C 313-326 disorder
       Region 2lxh C 327-384 order
       Region 2lxh C 384-384 high_rmsd
       Region 2lxh C 385-393 disorder
Seq 313-393,574-600 Hetero dimer : IID00307Complex
 Evidence X-RAY 4lad B Reference
       Region 4lad B 313-338 disorder
       Region 4lad B 339-380 order
       Region 4lad B 381-393 disorder
       Region 4lad B 574-599 order
       Region 4lad B 600-600 disorder
Seq 327-384,574-600 Hetero trimer : IID00307Complex
 Evidence NMR 2lxp B Reference
       Region 2lxp B 574-600 order
 Evidence NMR 2lxp C Reference
       Region 2lxp C 327-384 order
Seq 452-504 Monomer :
 Evidence NMR 2ejs A Reference
       Region 2ejs A 452-502 order
       Region 2ejs A 452-453 high_rmsd
       Region 2ejs A 502-502 high_rmsd
 Evidence NMR 2lvn C Reference
       Region 2lvn C 453-504 order
       Region 2lvn C 453-453 high_rmsd
       Region 2lvn C 502-504 high_rmsd
 Evidence X-RAY 4g3o A Reference
       Region 4g3o A 456-498 order
Seq 453-504 Hetero dimer : P0CG48
 Evidence NMR 2lvo C Reference
       Region 2lvo C 453-504 order
Seq 453-504 Hetero trimer : P0CG48
 Evidence NMR 2lvp C Reference
       Region 2lvp C 453-504 order
 Evidence NMR 2lvq D Reference
       Region 2lvq D 453-504 order
Seq 573-600 Hetero dimer : IID00307Complex
 Evidence X-RAY 3h8k B Reference
       Region 3h8k B 573-600 order
Seq 574-601 Hetero trimer : IID50078Complex
 Evidence X-RAY 3fsh C Reference
       Region 3fsh C 574-579 disorder
       Region 3fsh C 580-600 order
       Region 3fsh C 601-601 disorder
Seqdisorder 579-600
 Evidence NMR Reference
       Region 579-600 disorder
Seq 622-640 Hetero dimer : IID00201Complex
 Evidence X-RAY 3tiw C Reference
       Region 3tiw C 622-639 order
       Region 3tiw C 640-640 disorder
 Evidence X-RAY 3tiw D Reference
       Region 3tiw D 622-640 order
SeqProS verified 579-600 Hetero trimer : IID50078Complex
       Region 3fsh C 580-600 order
       Region 579-600 disorder
SeqProS verified 579-600 Hetero dimer : IID00307Complex
       Region 3h8k B 573-600 order
       Region 579-600 disorder
Seqphosphorylation
    542-542 Phosphoserine
    523-523 Phosphoserine
    516-516 Phosphoserine
 
Prediction
NeProc
Disorder 1-7,20-24,185-186,385-464,499-643
Order 8-19,25-42,49-184,187-384,465-498
ProS 1-7,20-24,185-186,418-438,567-571,580-600,623-639
AlphaFold
Disorder 1-12,39-67,285-287,337-338,384-424,429-430,433-434,436-436,438-453,499-571,573-573,601-621,640-643
Order 13-38,68-284,288-336,339-383,425-428,431-432,435-435,437-437,454-498,572-572,574-600,622-639
Pfam Hmmer
PF00097 341-378 2e-09
PF02845 456-497 5.9e-14
SEG 55-71 ,624-637
Function
Function in SwissProt
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 (PubMed:10456327, PubMed:11724934, PubMed:12670940, PubMed:19103148, PubMed:24424410, PubMed:28604676). Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of endoplasmic reticulum-associated degradation (ERAD) (PubMed:10456327, PubMed:11724934, PubMed:19103148, PubMed:24424410). 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 (PubMed:16168377, PubMed:22143767). 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 (PubMed:23223569). The ubiquitinated HMGCR is then released from the ER into the cytosol for subsequent destruction (PubMed:16168377, PubMed:22143767, PubMed:23223569). 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 (PubMed:28604676). Catalyzes ubiquitination and subsequent degradation of INSIG1 when cells are depleted of sterols (PubMed:17043353). Mediates polyubiquitination of INSIG2 at 'Cys-215' in some tissues, leading to its degradation (PubMed:31953408). Also regulates ERAD through the ubiquitination of UBL4A a component of the BAG6/BAT3 complex (PubMed:21636303). Also acts as a scaffold protein to assemble a complex that couples ubiquitination, retranslocation and deglycosylation (PubMed:21636303). Mediates tumor invasion and metastasis as a receptor for the GPI/autocrine motility factor (PubMed:10456327). 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 (PubMed:31073040).