Dihydrouridine synthase. Catalyzes the NADPH-dependent synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs (PubMed:15994936, PubMed:26429968, PubMed:30149704, PubMed:34798057). Negatively regulates the activation of EIF2AK2/PKR (PubMed:18096616). 5,6-dihydrouridine(20) in tRNA + NADP(+) = H(+) + NADPH + uridine(20) in tRNA Interacts with EPRS1. Interacts (via DRBM domain) with PRKRA and EIF2AK2/PKR (via DRBM 1 domain). Mainly at the endoplasmic reticulum. Weak expression in heart, placenta and skeletal muscle. Up-regulated in most lung cancer cells (at protein level). Efficient dihydrouridine synthesis requires the presence of both the catalytic domain and the C-terminal RNA-binding DRBM domain. Belongs to the Dus family. Dus2 subfamily.