ADP-ribosylation is a post-translational modification that is catalysed by ADP-ribosyltransferases (ARTs). This modification affects the functions of proteins across a diverse range of cellular pathways and processes. ADP-ribosylhydrolases act in opposition, to remove the modifications.

Nomenclature for the ADP-ribosyltransferases follows the recommendations from Lüscher et al. (2022) [1]. This nomenclature subclassifies the enzymes as:

Poly-ADP-ribosylating (PARylating) ARTs
The PARylating subfamily contains the well known poly-ADP-ribose polymerases (the 'original' PARPs) PARP1 and PARP2 and the tankyrases TNKS and TNKS2. These enzymes share a conserved H-Y-E catalytic motif, and they all reside in the nucleus.

Mono-ADP-ribosylating (MARylating) ARTs
The MARylating subfamily is larger with 11 human genes encoding the enzymes PARP3, -4, -6, -7 (TIPARP), -8, -10, -11, -12, -14, -15, -16). The catalytic triad for the MARylating enzymes retains the H-Y residues with the third position being a variable hydrophobic amino acid (E, I, L or Y). Subcellularly the MARylating enzymes are found in the nucleus and/or the cytosol.

ADP-ribosyltransferases are therapeutic targets, with several PARP1/2 inhibitors already in clinical use as antineoplastic agents. Atamparib (RBN2397) is the first clinical candidate that selectively inhibits MARylating PARP7.

1. Lüscher B, Ahel I, Altmeyer M, Ashworth A, Bai P, Chang P, Cohen M, Corda D, Dantzer F, Daugherty MD et al.. (2022) ADP-ribosyltransferases, an update on function and nomenclature. FEBS J, 289 (23): 7399-7410. [PMID:34323016]