NHL repeat domain of the tripartite motif-containing protein 2 (TRIM2) and related proteins
The E3 ubiquitin-protein ligase TRIM2 is responsible for ubiquinating the apoptosis-inducing Bcl-2-interacting mediator of cell death (Bim), when the latter is phosphorylated by p42/p44 MAPK. TRIM2 regulates the ubiquitination of neurofilament light subunit (NF-L), deficiencies in TRIM2 result in increased NF-L levels in axons and subsequent axonopathy. TRIM2 is also involved in regulating axon outgrowth during development; it contains RING and BBOX domains, the NHL repeat domain is located at its C-terminus. The NHL (NCL-1, HT2A and LIN-41) repeat is found in multiple tandem copies, typically as 6 instances. It is about 40 residues long and resembles the WD repeat and other beta-propeller structures.