InterPro domain: IPR022170

MUL1 is a multifunctional E3 ubiquitin ligase anchored in the outer mitochondrial membrane with its RING finger domain facing the cytoplasm. Mul1 functions as a ubiquitin ligase to ubiquitinate molecules such as mitofusin2 (Mfn2), Akt, p53 and ULK1, through its RING finger domain, leading to proteins degradation. Moreover, Mul1 can also act as a small ubiquitin-like modifiers (SUMO) E3 ligase to sumoylate proteins such as dynamin-related protein 1 (Drp1), enhancing protein stabilization [ 1 ]. It plays a role in the control of mitochondrial morphology, promotes mitochondrial fragmentation and influences mitochondrial localisation [ 2 ]. When over-expressed in human cells, it activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis [ 3 ]. MUL1 has also been shown to regulate RIG-I mediated antiviral response [ 4 ].

Ubiquitin E3 ligase SP1 associates with TOC (translocon at the outer envelope membrane of chloroplasts) complexes and mediates ubiquitination of TOC components, promoting their degradation. SP1-mediated regulation of chloroplast protein import contributes to the organellar proteome changes that occur during plant development [ 5 ]. It is also important for stress tolerance in plants [ 6 ].

This domain is found in mitochondrial ubiquitin ligase activator of NFKB 1 (MULAN, also known as MUL1) from animals and ubiquitin E3 Ligase SP1/SP2/SPL1/SPL2 from Arabidopsis.

1. Mitochondrial E3 ubiquitin ligase 1: A key enzyme in regulation of mitochondrial dynamics and functions. Mitochondrion 28, 49-53
2. Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers. Curr. Biol. 18, 102-8
3. GIDE is a mitochondrial E3 ubiquitin ligase that induces apoptosis and slows growth. Cell Res. 18, 900-10
4. Mitochondrially localised MUL1 is a novel modulator of antiviral signaling. Immunol. Cell Biol. 91, 321-30
5. Chloroplast biogenesis is regulated by direct action of the ubiquitin-proteasome system. Science 338, 655-9
6. Regulation of Chloroplast Protein Import by the Ubiquitin E3 Ligase SP1 Is Important for Stress Tolerance in Plants. Curr. Biol. 25, 2527-34