MUL1
Domain
The zinc finger domain is required for E3 ligase activity.
Function
Exhibits weak E3 ubiquitin-protein ligase activity (PubMed:18591963, PubMed:19407830, PubMed:22410793). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates (PubMed:18591963, PubMed:19407830, PubMed:22410793). Can ubiquitinate AKT1 preferentially at 'Lys-284' involving 'Lys-48'-linked polyubiquitination and seems to be involved in regulation of Akt signaling by targeting phosphorylated Akt to proteasomal degradation (PubMed:22410793). Mediates polyubiquitination of cytoplasmic TP53 at 'Lys-24' which targets TP53 for proteasomal degradation, thus reducing TP53 levels in the cytoplasm and mitochondrion (PubMed:21597459). Proposed to preferentially act as a SUMO E3 ligase at physiological concentrations (PubMed:19407830). Plays a role in the control of mitochondrial morphology by promoting mitochondrial fragmentation, and influences mitochondrial localization (PubMed:18207745, PubMed:18213395, PubMed:19407830). Likely to promote mitochondrial fission through negatively regulating the mitochondrial fusion proteins MFN1 and MFN2, acting in a pathway that is parallel to the PRKN/PINK1 regulatory pathway (PubMed:24898855). May also be involved in the sumoylation of the membrane fission protein DNM1L (PubMed:18207745, PubMed:19407830). Inhibits cell growth (PubMed:18591963, PubMed:22410793). When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis (PubMed:23399697). Involved in the modulation of innate immune defense against viruses by inhibiting RIGI-dependent antiviral response (PubMed:23399697). Can mediate RIGI sumoylation and disrupt its polyubiquitination (PubMed:23399697).
Pathway
Protein modification; protein ubiquitination.
Protein modification; protein sumoylation.
Post-translational modifications
Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30.
Tissue Specificity
Widely expressed with highest levels in the heart, skeletal muscle, placenta, kidney and liver. Barely detectable in colon and thymus.
Cellular localization
- Mitochondrion outer membrane
- Multi-pass membrane protein
- Peroxisome
- Transported in mitochondrion-derived vesicles from the mitochondrion to the peroxisome.
Alternative names
C1orf166, GIDE, MAPL, MULAN, RNF218, MUL1, Mitochondrial ubiquitin ligase activator of NFKB 1, E3 SUMO-protein ligase MUL1, E3 ubiquitin-protein ligase MUL1, Growth inhibition and death E3 ligase, Mitochondrial-anchored protein ligase, Protein Hades, Putative NF-kappa-B-activating protein 266, RING finger protein 218, RING-type E3 ubiquitin transferase NFKB 1