DALRD3 is an uncharacterized protein containing a carboxy-terminal sequence homologous to the “DALR” anticodon-binding domain found in arginyl tRNA synthetases from Archaea to Eukaryotes36. The DALR domain is named after characteristic conserved amino acids present in the primary protein sequence and folds into an all alpha helical structure as observed in S. cerevisiae arginyl tRNA synthetase36–38. In contrast to the carboxy-terminus, the amino-terminal portion of DALRD3 contains no recognizable motifs or domains and is specific only to DALRD3 homologs. While no DALRD3 homologs have yet been identified in single-celled eukaryotes or invertebrates, DALRD3 homologs can be detected in all sequenced vertebrates ranging from primitive jawless fishes to mammals39,40. Within vertebrates, the canonical DALR domain is found in cytoplasmic arginyl-tRNA synthetase 1 (RARS1) and mitochondrial arginyl-tRNA synthetase 2 (RARS2) in addition to DALRD3 (Fig. 1e). Unlike RARS1 and RARS2, however, DALRD3 lacks a recognizable tRNA synthetase catalytic motif, thereby suggesting a distinct function for DALRD3 outside of tRNA aminoacylation.
