ABSTRACTA gene (eft-1) encoding an elongation factor 2-like protein was isolated from a region adjacent to the polyubiquitin gene,ubq-1, ofCaenorhabditis elegans. Sequence analysis of genomic and cDNA clones revealed that the deduced amino acid sequence of the protein (EFT-1) is 38% identical to that of mammalian andDrosophilaelongation factor 2 (EF-2). The entireeft-1gene is approximately 3.8 kb in length and contains 5 exons separated by short introns of 46–75 bp. The 2,547-bp open reading frame predicts a protein of 849 amino acid residues (calculated Mr, 96,151). Conserved sequences shared among a variety of GTP-binding proteins including EF-2 are found in the amino-terminal third of EFT-1. The carboxy-terminal half contains regions with 40–57% similarity (including conservative changes) with segments characteristic of EF-2 and its prokaryotic homolog, EF-G. However, the histidyl residue target for ADP-ribosylation of EF-2 by diphtheria toxin is replaced by tyrosine in EFT-1. Southern and Northern blot analyses indicate thateft-1is a single-copy gene that is expressed at all stages of nematode development. Amplification of fragments encoding highly conserved regions of EF-2 using the polymerase chain reaction led to the isolation of a fragment encoding the modifiable histidyl residue and which likely represents part of theC. elegansEF-2 gene (eft-2). This suggests that EFT-1 is not theC. eleganshomolog of EF-2, but a closely related prot