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.

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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]