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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.
Database page citation:
ADP-ribosyltransferases (ARTs). Accessed on 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1095.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2019) The Concise Guide to PHARMACOLOGY 2019/20: Enzymes. Br J Pharmacol. 176 Issue S1: S297-S396.