NMRAL1

This gene encodes an NADPH sensor protein that preferentially binds to NADPH. The encoded protein also negatively regulates the activity of NF-kappaB in a ubiquitylation-dependent manner. It plays a key role in cellular antiviral response by negatively regulating the interferon response factor 3-mediated expression of interferon beta. Alternative splicing of this gene results in multiple transcript variants.

Full Name

NmrA-like family domain containing 1

Function

Redox sensor protein. Undergoes restructuring and subcellular redistribution in response to changes in intracellular NADPH/NADP+ levels. At low NADPH concentrations the protein is found mainly as a monomer, and binds argininosuccinate synthase (ASS1), the enzyme involved in nitric oxide synthesis. Association with ASS1 impairs its activity and reduces the production of nitric oxide, which subsecuently prevents apoptosis. Under normal NADPH concentrations, the protein is found as a dimer and hides the binding site for ASS1. The homodimer binds one molecule of NADPH. Has higher affinity for NADPH than for NADP+. Binding to NADPH is necessary to form a stable dimer.

Cellular Location

Cytoplasm
Cytoplasm, perinuclear region
Nucleus
Under normal redox growth conditions localizes in the cytoplasm and perinuclear region. Nuclear localization is promoted by increased intracellular nitric oxide and reduced NADPH/NADP+ ratios.