NmrA-like family domain-containing protein 1 (NMRAL1)

NmrA-like family domain-containing protein 1 (NMRAL1, also known as HSCARG or SDR48A1) is a redox sensor protein widely conserved in mammals and other higher animals[1][5]. It contains a Rossmann fold and is structurally similar to, but functionally distinct from, enzymatic short-chain dehydrogenases/reductases (SDR): it binds NADPH selectively but does not catalyze metabolic reactions due to a lack of key catalytic residues[1]. NMRAL1/HSCARG acts as an intracellular NADPH sensor, existing primarily as a dimer under normal reducing conditions and as a monomer when NADPH levels fall, at which point it interacts with partners such as argininosuccinate synthase (ASS1), inhibiting nitric oxide production and modulating the immune response[2][5]. It negatively regulates the NF-κB and RLR innate immune signaling pathways, modulates cellular redox balance by suppressing ROS and NO production, and, during oxidative stress, relocates to the nucleus to influence the DNA damage response[1][3][5]. Although identified as playing roles in several disease contexts (notably some corneal dystrophies and possibly cancer and immune disorders), NMRAL1 is not currently considered a direct therapeutic target, and no drugs are known to act specifically on it[2][5].

Other names

HSCARGSDR48A1NmrA-like redox sensor 1FLJ25918short chain dehydrogenase/reductase family 48A member 1nmrA-like family domain containing 1