|PROSITE documentation PDOC51858 [for PROSITE entry PS51858]|
Ubiquitin is a highly conserved 76-residue protein that is found in eukaryotes but not in bacteria and archaea. A wide variety of proteins are post-translationally modified by covalent attachment of a single or multiple molecule(s) of ubiquitin, a process called ubiquitination or ubiquitylation. Following the discovery of ubiquitin, a number of ubiquitin-like proteins have been found, including small ubiquitin-like modifiers (SUMOs), interferon-stimulated gene 15 (ISG15), neural precursor cell expressed, developmentally down regulated 8 (NEDD8), Autophygy 8 (Atg8), and Atg12. Conjugation of these modifiers to protein substrates occurs through sequential reactions that are performed by multiple enzymes. Protein ubiquitination is reversed by deubiquitinases (also known as deubiquitinylases) that cleave the isopeptide bond between ubiquitin and its target protein. Likewise, removal of ubiquitin-like proteins from the conjugated proteins is performed by structurally diverse isopeptidases, including deSUMOylases, deISGylases, and deNEDDylases, which cleave off SUMO, ISG15, and NEDD8 from the substrate proteins, respectively. The PPPDE (after Permutated Papain fold Peptidase of DsRNA viruses and Eukaryotes) domain is a cysteine isopeptidase that exhibits a deSUMOylase activity in PPPDE2 (DeSI-1) and a deubiquinating activity in PPPDE1 (DeSI-2). The PPPDE domain is restricted to eukaryotes, dsRNA viruses and one single stranded DNA virus [1,2,3,4].
The PPPDE domain can be described as a mixed α/β-fold composed of six β-strands and six α-helices. Five β-strands (β1-β5) form a highly curved central β-sheet that is stacked by a pair of antiparallel α-helices (α2 and α3) and surrounded by α1 and α4 (see <PDB:2WP7>). The PPPDE domain has a papain-like fold, in which a catalytic dyad is formed by a conserved N-terminal histidine residue on a β-strand (β2) and a conserved C-terminal cysteine residue on a following α-helix (α3) (the H-C configuration) as opposed to the C-H configuration seen in the classical papain-like peptidases. The sulfur atom of the Cys and the imidazole ring nitrogen of the His form a catalytic dyad in which the His can polarize the Cys to make it reactive .
Some proteins known to contain a PPPDE domain are listed below:
The profile we developed covers the entire PPPDE domain.Last update:
February 2018 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Iyer L.M. Koonin E.V. Aravind L.|
|Title||Novel predicted peptidases with a potential role in the ubiquitin signaling pathway.|
|Source||Cell Cycle 3:1440-1450(2004).|
|2||Authors||Suh H.-Y. Kim J.-H. Woo J.-S. Ku B. Shin E.J. Yun Y. Oh B.-H.|
|Title||Crystal structure of DeSI-1, a novel deSUMOylase belonging to a putative isopeptidase superfamily.|
|3||Authors||Shin E.J. Shin H.M. Nam E. Kim W.S. Kim J.-H. Oh B.-H. Yun Y.|
|Title||DeSUMOylating isopeptidase: a second class of SUMO protease.|
|Source||EMBO. Rep. 13:339-346(2012).|
|4||Authors||Xie X. Wang X. Jiang D. Wang J. Fei R. Cong X. Wei L. Wang Y. Chen H.|
|Title||PPPDE1 is a novel deubiquitinase belonging to a cysteine isopeptidase family.|
|Source||Biochem. Biophys. Res. Commun. 488:291-296(2017).|
|5||Authors||Han H. Heo T.Y. Ryu I.W. Kim K. Lim C.-J.|
|Title||Defensive roles of Sdu1, a PPPDE superfamily member with ubiquitin C-terminal hydrolase activity, against thermal stress in Schizosaccharomyces pombe.|
|Source||Kor. J. Microbiol. 51:329-337(2015).|