TRIM72
Domain
The RING domain is flexible in both the dimer and oligomer (By similarity). Binding to the negatively charged phosphatidylserine lipids is mediated by the positively charged PRYSPRY domains and is inhibited by Ca(2+) (By similarity).
Function
Muscle-specific E3 ubiquitin-protein ligase that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at injury sites (PubMed:36944613). Its ubiquitination activity is mediated by E2 ubiquitin-conjugating enzymes UBE2D1, UBE2D2 and UBE2D3 (By similarity). Acts as a sensor of oxidation: upon membrane damage, entry of extracellular oxidative environment results in disulfide bond formation and homooligomerization at the injury site (By similarity). This oligomerization acts as a nucleation site for recruitment of TRIM72-containing vesicles to the injury site, leading to membrane patch formation (By similarity). Probably acts upstream of the Ca(2+)-dependent membrane resealing process (By similarity). Required for transport of DYSF to sites of cell injury during repair patch formation (By similarity). Regulates membrane budding and exocytosis (By similarity). May be involved in the regulation of the mobility of KCNB1-containing endocytic vesicles (By similarity).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Disulfide bond formation at Cys-242 occurs in case of membrane damage that cause the entry of the oxidized milieu of the extracellular space, resulting in homooligomerization.
S-nitrosylation at Cys-144 stabilizes TRIM72 and protects against oxidation-induced protein degradation and cell death.
Sequence Similarities
Belongs to the TRIM/RBCC family.
Cellular localization
- Cell membrane
- Sarcolemma
- Cytoplasmic vesicle membrane
- Tethered to plasma membrane and cytoplasmic vesicles via its interaction with phosphatidylserine.
Alternative names
MG53, TRIM72, Tripartite motif-containing protein 72, Mitsugumin-53, Mg53