An Evolutionary Perspective on the Origin, Conservation and Binding Partner Acquisition of Tankyrases

Abstract

Tankyrases are poly-ADP-ribosyltransferases that regulate many crucial and diverse cellular processes in humans such as Wnt signaling, telomere homeostasis, mitotic spindle formation and glucose metabolism. While tankyrases are present in most animals, functional differences across species may exist. In this work, we confirm the widespread distribution of tankyrases throughout the branches of multicellular animal life and identify the single-celled choanoflagellates as earliest origin of tankyrases. We further show that the sequences and structural aspects of TNKSs are well-conserved even between distantly related species. We also experimentally characterized an anciently diverged tankyrase homolog from the sponge Amphimedon queenslandica and show that the basic functional aspects, such as poly-ADP-ribosylation activity and interaction with the canonical tankyrase binding peptide motif, are conserved. Conversely, the presence of tankyrase binding motifs in orthologs of confirmed interaction partners varies greatly between species, indicating that tankyrases may have different sets of interaction partners depending on the animal lineage. Overall, our analysis suggests a remarkable degree of conservation for tankyrases, and that their regulatory functions in cells have likely changed considerably throughout evolution.

Oligomerisation mediated by the D2 domain of DTX3L is critical for DTX3L-PARP9 reading function of mono-ADP-ribosylated androgen receptor

“…We, therefore, first identified the sequence identity between human DTX3L full-length amino acid sequence and its orthologues in model organisms, which represent different taxonomy levels (Figure 3C). From the sequence identity, we were able to conclude that DTX3L, similar to PARP9, is not a particularly conserved protein (Sowa et al, 2022). Furthermore, the identity between orthologues was mostly observed in the RD regions (Figure 1A) of the protein while the remaining domains showed a variable degree of identity.…”

Oligomerization mediated by the D2 domain of DTX3L is critical for DTX3L‐PARP9 reading function of mono‐ADP‐ribosylated androgen receptor

“…We, therefore, first identified the sequence identity between human DTX3L full‐length amino acid sequence and its orthologs in model organisms, which represent different taxonomy levels (Figure 3c ). From the sequence identity, we were able to conclude that DTX3L, similar to PARP9, is not a particularly conserved protein (Sowa et al, 2022 ). Furthermore, the identity between orthologs was mostly observed in the RD regions (Figure 1a ) of the protein while the remaining domains showed a variable degree of identity.…”