Tripartite Motif Containing Protein 2 (TRIM2)

TRIM2 is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic filaments. Its function has not been identified. TRIM2, highly expressed in the nervous system, is an UbcH5a-dependent ubiquitin ligase. TRIM2 binds to neurofilament light subunit (NF-L) and regulates NF-L ubiquitination. Mice deficient in TRIM2 have increased NF-L level in axons and NF-L-filled axonal swellings in cerebellum, retina, spinal cord, and cerebral cortex. The axonopathy is followed by progressive neurodegeneration accompanied by juvenile-onset tremor and ataxia. TRIM2 is an ubiquitin ligase and point to a mechanism regulating NF-L metabolism through an ubiquitination pathway that, if deregulated, triggers neurodegeneration.