The results obtained here show that LOC56985, though structurally similar to purple-acid phosphatases (figure 3), shows no sequence similarity to them (figure 1). The characteristic sequence motifs associated with PAPs indicate that LOC56985 shares some homology with them, however the conserved region (GNHE/D) appears common across all phosphoresterases. Vertical gene transmission appears to be the major form of evolution with the exception of Trypanosoma cruzi which may be a candidate for lateral gene transmission. Othologues have been found in α-proteobacteria and green sulfur bacteria, the protozoan T. cruzi, green algae, mosses, higher plants (tracheophytes), and vertebrates.
The substrate specificity of LOC56985 is still a mystery, however a recent, yet to be published manuscript provides experimental evidence that the rat ortholog, A9Y0H8 functions as a Mn2+ dependant ADP-ribose/ CDP-alcohol pyrophosphatase (ADPRibase-Mn), an intracellular regulator of ion channel activity (Canales et al. 2008). High-throughput gene expression data showed that LOC56985 and its orthologs are predominantly expressed in immune tissues in mammals. The restriction of LOC56985 orthologs to vertebrates among animals further supports the probability of an immune specific role. ADPRibase-Mn, and hence orthologs in other vertebrates, may have a signalling role in immune cells where ADP-Ribose acts as a second messenger of stress. ADP-Ribose is an activator of transient receptor potential melastatin channel-2 (TRPM2), which participates in Ca2+ mediated cell death.As demonstrated by tissue-specific expression in mammals, the cellular role(s) of LOC56985 orthologs are likely to differ between animals and plants. However, the relatively high degree of sequence conservation observed between animal and plant orthologs suggest that the principle biochemical role is likely to be similar in both kingdoms.
Further experiments are needed to ascertain substrates and metal ligands which associate with LOC56985 orthologs in various phyla. Additional crystal structures should be determined using specific substrates and ligands to better understand the mechanism of enzyme action. On current evidence, LOC56985 can be described as a PAP-like metallo-dependant phosphatase (PMDP).