A novel predicted ADP-ribosyltransferase-like family conserved in eukaryotic evolution

Zbigniew Wyzewski, Marcin Gradowski, Marianna Krysińska, Małgorzata Dudkiewicz, Krzysztof Pawłowski

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


The presence of many completely uncharacterized proteins, even in well-studied organisms such as humans, seriously hampers full understanding of the functioning of the living cells. ADP-ribosylation is a common post-translational modification of proteins; also nucleic acids and small molecules can be modified by the covalent attachment of ADP-ribose. This modification, important in cellular signalling and infection processes, is usually executed by enzymes from the large superfamily of ADP-ribosyltransferases (ARTs). Here, using bioinformatics approaches, we identify a novel putative ADP-ribosyltransferase family, conserved in eukaryotic evolution, with a divergent active site. The hallmark of these proteins is the ART domain nestled between flanking leucine-rich repeat (LRR) domains. LRRs are typically involved in innate immune surveillance. The novel family appears as putative novel ADP-ribosylationrelated actors, most likely pseudoenzymes. Sequence divergence and lack of clearly detectable ''classical'' ART active site suggests the novel domains are pseudoARTs, yet atypical ART activity, or alternative enzymatic activity cannot be excluded. We propose that this family, including its human member LRRC9, may be involved in an ancient defense mechanism, with analogies to the innate immune system, and coupling pathogen detection to ADP-ribosyltransfer or other signalling mechanisms.

Original languageEnglish (US)
Article number11051
StatePublished - Mar 10 2021


  • ADP-ribosyltransferases
  • Evolution
  • Protein domains
  • Protein structure and function prediction
  • Pseudoenzymes

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences


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