MUL1 Recombinant Rabbit Monoclonal Antibody [PSH15-17]

Function

Mitochondrial E3 ubiquitin protein ligase 1 (MUL1) is an enzyme that in humans is encoded by the MUL1 gene on chromosome 1. This enzyme localizes to the outer mitochondrial membrane, where it regulates mitochondrial morphology and apoptosis through multiple pathways, including the Akt, JNK, and NF-κB. Its proapoptotic function thus implicates it in cancer and Parkinson's disease. Exhibits weak E3 ubiquitin-protein ligase activity. 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. 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 proteosomal degradation. Proposed to preferentially act as a SUMO E3 ligase at physiological concentrations. Is anchored in the outer mitochondrial membrane. Plays a role in the control of mitochondrial morphology. Promotes mitochondrial fragmentation and influences mitochondrial localization. The function may implicate its ability to sumoylate DNM1L. Has been observed to shuttle between the mitochondria and peroxisome, where it may also help regulate peroxisome fission. Inhibits cell growth. When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis. Involved in the modulation of innate immune defense against viruses by inhibiting DDX58-dependent antiviral response. Can mediate DDX58 sumoylation and disrupt its polyubiquitination. Can also activate NF-κB to initiate mitochondria-to-nucleus signaling under stress.

Background References

1. Lee MS et al. MUL1-RING recruits the substrate, p53-TAD as a complex with UBE2D2-UB conjugate. FEBS J. 2022 Jun

2. Huang Q et al. Ginsenoside compound K protects against cerebral ischemia/reperfusion injury via Mul1/Mfn2-mediated mitochondrial dynamics and bioenergy. J Ginseng Res. 2023 May

Subcellular Location

Mitochondrion outer membrane, Peroxisome.

UNIPROT

SwissProt: Q969V5 Human

SwissProt: Q8VCM5 Mouse

Entrez Gene: 298576 Rat

Synonyms