NmrA-Like Family Domain Containing 1 (NMRAL1), also known as NmrA-Like Redox Sensor 1, is a protein encoded by the NMRAL1 gene in humans. This protein plays a crucial role in cellular redox homeostasis and is involved in various biological processes, including the regulation of nitric oxide synthesis and the cellular antiviral response.
NMRAL1 functions as a redox sensor protein. It undergoes structural changes and subcellular redistribution in response to fluctuations in intracellular NADPH/NADP+ levels . At low NADPH concentrations, NMRAL1 exists primarily as a monomer and binds to argininosuccinate synthase (ASS1), an enzyme involved in nitric oxide synthesis . This binding impairs ASS1 activity, reducing nitric oxide production and preventing apoptosis . Under normal NADPH concentrations, NMRAL1 forms a stable dimer, which hides the binding site for ASS1 .
NMRAL1 negatively regulates the activity of NF-kappaB in a ubiquitylation-dependent manner . It also plays a critical role in the cellular antiviral response by negatively regulating the interferon response factor 3-mediated expression of interferon-beta . Alternative splicing of the NMRAL1 gene results in multiple transcript variants, which may have distinct regulatory functions .