Plants and yeasts have no known endogenous AMPylating enzymes, but animal genomes are endowed with a single copy of a gene encoding a Fic-domain AMPylase, that was likely acquired by an early ancestor of animals via horizontal gene transfer from a prokaryote. The human protein referred to commonly as FICD, had been previously identified as Huntingtin associated protein E (HypE; an assignment arising from a yeast two-hybrid screen, but of questionable relevance, as Huntingtin and HypE/FICD are localised to different cellular compartments). CG9523 Homologues in Drosophila melanogaster (CG9523) and C. elegans (Fic-1) have also received attention. In all animals FICD has a similar structure. It is a type II transmembrane domain protein, with a short cytoplasmic domain followed by membrane anchor that holds the protein in the endoplasmic reticulum (ER) and long C-terminal portion that resides in ER and encompasses tetratricopeptide repeats (TPRs) followed by a catalytic Fic domain.