Fig. 1.

TNKS1/2 and RNF146 structure and functional classification of tankyrase substrates. Both tankyrases share a similar structure that consist in the C-terminal catalytic PARP domain that catalyze the synthesis and addition of linear PAR chains onto their substrates, the SAM domain responsible for the formation of multimeric structures with other tankyrases and the ankyrin domain divided in five ankyrin domain clusters (ARC1–5) which mediate the recognition and binding to the substrates (except for ARC3). In the case of TNKS1 there is also an HPS region with unknown function (a). The substrates of tankyrase can be classified into four categories according to the biological response that trigger when they interact with TNKS1/2: proteasomal degradation, cataytic inhibition, scafffolding function and complexes disruption (b). RNF146 presents two characterized domains in the N-region: the RING domain responsible for the E3-ligase activity and the WWE domain, which recognizes the iso-ADP-ribose moiety present in the PARylated substrates via its PAR-binding motif (c)