UBE2D1-dependent E3 ubiquitin-protein ligase that mediates the ubiquitination of NEFL and of phosphorylated BCL2L11. Plays a neuroprotective function. May play a role in neuronal rapid ischemic tolerance. S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Interacts with myosin V; myosin V may not be a substrate for ubiquitination. Interacts with NEFL. Interacts with phosphorylated BCL2L11. Highly expressed in the cerebellum, hippocampus, retina and spinal cord. In the cerebellum, strongest expression in Purkinje cells and in the deep cerebellar nuclei. In retina, high expression in the ganglionic cell layer, inner nuclear layer and inthe outer plexiform layer. Particularly high expression in the hippocampus, in pyramidal cells of CA1-CA3 hippocampal areas and ingranule cells of the dentate gyrus. At 12.5 dpc, expressed in the developing nervous system, particularly in the spinal cord, dorsal rootganglia, hindbrain and midbrain. The interaction with myosin V is dependent upon its NHL repeats, which form a beta-propeller (NHL) domain containing six blades. RING-type zinc finger-dependent and UBE2D1-dependent autoubiquitination. Mutant mice are indistinguishable from wild type until about 1.5 months of age, when they begin to show intention tremor, followed by gait ataxia. At this stage, neurons exhibit axonal swellings, which consist of the accumulation of disorganized neurofilaments and microtubules, mitochondria and vesicles. In later stages, mutant animals suffer from episodes of spontaneous generalized seizures, a phenotype caused by progressive loss of Purkinje cells through apoptosis. At 4 months of age, retinas in mutant mice display decreased thickness of the inner nuclear layer and a reduced number of ganglionic cells. The outer plexiform layer is also reduced, whereas the size of the photoreceptor layer is not altered. Belongs to the TRIM/RBCC family. Extended N-terminus.