| IED ID | IndEnz0002014507 |
| Enzyme Type ID | protease014507 |
| Protein Name |
E3 ubiquitin-protein ligase AMFR EC 2.3.2.36 Autocrine motility factor receptor AMF receptor RING finger protein 45 gp78 |
| Gene Name | AMFR RNF45 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MPLLFLERFPWPSLRTYTGLSGLALLGTIISAYRALSQPEAGPGEPDQLTASLQPEPPAPARPSAGGPRARDVAQYLLSDSLFVWVLVNTACCVLMLVAKLIQCIVFGPLRVSERQHLKDKFWNFIFYKFIFIFGVLNVQTVEEVVMWCLWFAGLVFLHLMVQLCKDRFEYLSFSPTTPMSSHGRVLSLLVAMLLSCCGLAAVCSITGYTHGMHTLAFMAAESLLVTVRTAHVILRYVIHLWDLNHEGTWEGKGTYVYYTDFVMELTLLSLDLMHHIHMLLFGNIWLSMASLVIFMQLRYLFHEVQRRIRRHKNYLRVVGNMEARFAVATPEELAVNNDDCAICWDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSLNIADNNRVREEHQGENLDENLVPVAAAEGRPRLNQHNHFFHFDGSRIASWLPSFSVEVMHTTNILGITQASNSQLNAMAHQIQEMFPQVPYHLVLQDLQLTRSVEITTDNILEGRIQVPFPTQRSDSIRPALNSPVERPSSDQEEGETSAQTERVPLDLSPRLEETLDFGEVEVEPSEVEDFEARGSRFSKSADERQRMLVQRKDELLQQARKRFLNKSSEDDAASESFLPSEGASSDPVTLRRRMLAAAAERRLQKQQTS |
| Enzyme Length | 643 |
| Uniprot Accession Number | Q9UKV5 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-S-ubiquitinyl-L-cysteine.; EC=2.3.2.36; Evidence={ECO:0000269|PubMed:28604676, ECO:0000269|PubMed:31953408}; |
| DNA Binding | |
| EC Number | 2.3.2.36 |
| Enzyme Function | 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 (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). {ECO:0000269|PubMed:10456327, ECO:0000269|PubMed:11724934, ECO:0000269|PubMed:12670940, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:17043353, ECO:0000269|PubMed:19103148, ECO:0000269|PubMed:21636303, ECO:0000269|PubMed:22143767, ECO:0000269|PubMed:23223569, ECO:0000269|PubMed:24424410, ECO:0000269|PubMed:28604676, ECO:0000269|PubMed:31073040, ECO:0000269|PubMed:31953408}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:11724934, ECO:0000269|PubMed:16168377}. |
| nucleotide Binding | |
| Features | Beta strand (5); Chain (1); Compositional bias (2); Domain (1); Frameshift (1); Helix (7); Modified residue (3); Mutagenesis (4); Natural variant (1); Region (4); Sequence caution (1); Sequence conflict (4); Transmembrane (7); Zinc finger (1) |
| Keywords | 3D-structure;Endoplasmic reticulum;Lipoprotein;Membrane;Metal-binding;Palmitate;Phosphoprotein;Receptor;Reference proteome;Transferase;Transmembrane;Transmembrane helix;Ubl conjugation pathway;Wnt signaling pathway;Zinc;Zinc-finger |
| Interact With | Itself; O75477; O94905; O15503; Q9BVT8; P60604; P55072; P60605 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:11724934, ECO:0000269|PubMed:22728137}; Multi-pass membrane protein {ECO:0000269|PubMed:11724934}. Note=Palmitoylation promotes localization to the peripheral endoplasmic reticulum. {ECO:0000269|PubMed:22728137}. |
| Modified Residue | MOD_RES 516; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:18669648; MOD_RES 523; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:24275569; MOD_RES 542; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163 |
| Post Translational Modification | PTM: Palmitoylation of the RING-type zing finger by ZDHHC6 promotes localization to the peripheral endoplasmic reticulum. {ECO:0000269|PubMed:22728137}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (7); X-ray crystallography (5) |
| Cross Reference PDB | 2EJS; 2LVN; 2LVO; 2LVP; 2LVQ; 2LXH; 2LXP; 3FSH; 3H8K; 3TIW; 4G3O; 4LAD; |
| Mapped Pubmed ID | 15215856; 15358861; 15362974; 16055502; 16275660; 17353931; 18264092; 18417469; 18775313; 19084021; 19223579; 19549727; 19560420; 19690564; 21343306; 21900206; 23123110; 23232094; 23942235; 24820123; 26611529; |
| Motif | |
| Gene Encoded By | |
| Mass | 72,996 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 2.3.2.27; |