Protein family FAM241 in human and mouse.

FAM241B was isolated in a genome-wide inactivation screen for generation of enlarged lysosomes. FAM241B and FAM241A comprise protein family FAM241 encoding proteins of 121 and 132 amino acid residues, respectively. The proteins exhibit 25% amino acid sequence identity and contain a domain of unknown function (DUF4605; pfam15378) that is conserved from primitive multicellular eukaryotes through vertebrates.

Neuronal activity regulates Matrin 3 abundance and function in a calcium-dependent manner through calpain-mediated cleavage and calmodulin binding.

RNA-binding protein (RBP) dysfunction is a fundamental hallmark of amyotrophic lateral sclerosis (ALS) and related neuromuscular disorders. Abnormal neuronal excitability is also a conserved feature in ALS patients and disease models, yet little is known about how activity-dependent processes regulate RBP levels and functions. Mutations in the gene encoding the RBP Matrin 3 (MATR3) cause familial disease, and MATR3 pathology has also been observed in sporadic ALS, suggesting a key role for MATR3 in disease pathogenesis.