| IED ID | IndEnz0002008910 |
| Enzyme Type ID | protease008910 |
| Protein Name |
E3 ubiquitin-protein ligase RNF139 EC 2.3.2.27 RING finger protein 139 RING-type E3 ubiquitin transferase RNF139 Translocation in renal carcinoma on chromosome 8 protein |
| Gene Name | RNF139 TRC8 |
| 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 | MAAVGPPQQQVRMAHQQVWAALEVALRVPCLYIIDAIFNSYPDSSQSRFCIVLQIFLRLFGVFASSIVLILSQRSLFKFYTYSSAFLLAATSVLVNYYASLHIDFYGAYNTSAFGIELLPRKGPSLWMALIVLQLTFGIGYVTLLQIHSIYSQLIILDLLVPVIGLITELPLHIRETLLFTSSLILTLNTVFVLAVKLKWFYYSTRYVYLLVRHMYRIYGLQLLMEDTWKRIRFPDILRVFWLTRVTAQATVLMYILRMANETDSFFISWDDFWDLICNLIISGCDSTLTVLGMSAVISSVAHYLGLGILAFIGSTEEDDRRLGFVAPVLFFILALQTGLSGLRPEERLIRLSRNMCLLLTAVLHFIHGMTDPVLMSLSASHVSSFRRHFPVLFVSACLFILPVLLSYVLWHHYALNTWLFAVTAFCVELCLKVIVSLTVYTLFMIDGYYNVLWEKLDDYVYYVRSTGSIIEFIFGVVMFGNGAYTMMFESGSKIRAFMMCLHAYFNIYLQAKNGWKTFMNRRTAVKKINSLPEIKGSRLQEINDVCAICYHEFTTSARITPCNHYFHALCLRKWLYIQDTCPMCHQKVYIEDDIKDNSNVSNNNGFIPPNETPEEAVREAAAESDRELNEDDSTDCDDDVQRERNGVIQHTGAAAEEFNDDTD |
| Enzyme Length | 664 |
| Uniprot Accession Number | Q8WU17 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; Evidence={ECO:0000269|PubMed:17016439}; |
| DNA Binding | |
| EC Number | 2.3.2.27 |
| Enzyme Function | FUNCTION: E3-ubiquitin ligase; acts as a negative regulator of cell proliferation through mechanisms involving G2/M arrest and cell death (PubMed:10500182, PubMed:12032852, PubMed:17016439). Required for MHC class I ubiquitination in cells expressing the cytomegalovirus protein US2 before dislocation from the endoplasmic reticulum (ER) (PubMed:19720873). Affects SREBP processing by hindering the SREBP-SCAP complex translocation from the ER to the Golgi, thereby reducing SREBF2 target gene expression (PubMed:19706601, PubMed:20068067). Involved in the sterol-accelerated degradation of HMGCR (PubMed:22143767, PubMed:23223569). This is achieved through binding of RNF139 to INSIG1 and/or INSIG2 at the ER membrane (PubMed:22143767). In addition, interaction of RNF139 with AUP1 facilitates interaction of RNF139 with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase AMFR, leading to ubiquitination of HMGCR (PubMed:23223569). The ubiquitinated HMGCR is then released from the ER into the cytosol for subsequent destruction (PubMed:22143767, PubMed:23223569). Required for INSIG1 ubiquitination (PubMed:20068067). May be required for EIF3 complex ubiquitination (PubMed:20068067). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:12032852, ECO:0000269|PubMed:17016439, ECO:0000269|PubMed:19706601, ECO:0000269|PubMed:19720873, ECO:0000269|PubMed:20068067, ECO:0000269|PubMed:22143767, ECO:0000269|PubMed:23223569}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:17016439, ECO:0000269|PubMed:22143767}. |
| nucleotide Binding | |
| Features | Chain (1); Initiator methionine (1); Modified residue (4); Mutagenesis (5); Region (1); Sequence conflict (2); Transmembrane (12); Zinc finger (1) |
| Keywords | Acetylation;Chromosomal rearrangement;Endoplasmic reticulum;Membrane;Metal-binding;Phosphoprotein;Receptor;Reference proteome;Transferase;Transmembrane;Transmembrane helix;Ubl conjugation;Ubl conjugation pathway;Zinc;Zinc-finger |
| Interact With | P54253; Q8TCT9; P40337 |
| Induction | INDUCTION: Down-regulated by sterols (at protein level). {ECO:0000269|PubMed:20068067}. |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:12032852}; Multi-pass membrane protein {ECO:0000269|PubMed:12032852}. |
| Modified Residue | MOD_RES 2; /note="N-acetylalanine"; /evidence="ECO:0007744|PubMed:22814378"; MOD_RES 634; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 635; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 663; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" |
| Post Translational Modification | PTM: Autoubiquitinated. Ubiquitination is induced by sterol and leads to ist degradation via the ubiquitin-proteasome pathway. {ECO:0000269|PubMed:19706601}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 17539022; 18264092; 18417469; 19084021; 19549727; 19690564; 21343306; 22689053; 23232094; 26210183; 27998983; 28662643; 29519897; 30563842; 34106407; |
| Motif | |
| Gene Encoded By | |
| Mass | 75,994 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |