RPN8

PF3D7_0912900 (RPN8) is a conserved subunit of the 19S regulatory particle lid of the 26S proteasome in P. falciparum, a component inferred to be present since the last eukaryotic common ancestor (PMID:25943340). Comparative genomics places RPN8 in a dimer with Rpn11 (PSMD14), the pairing that in the lid catalyzes deubiquitylation of substrates entering the proteasome (PMID:25943340). RPN8 itself carries an inactive MPN- domain that lacks the catalytic residues required for metalloprotease activity, so unlike its partner Rpn11 it does not possess intrinsic deubiquitylase or deNeddylase activity in P. falciparum (PMID:31658303). Beyond its predicted lid membership and the domain-based inference of catalytic inactivity, no direct biochemical or genetic characterization of PF3D7_0912900 has been reported in the available corpus.

1. 2015 Low

   Establishing whether RPN8 is a genuine constituent of the parasite proteasome addressed whether P. falciparum retains the canonical lid architecture; comparative genomics placed RPN8 as a conserved 19S lid subunit dimerizing with Rpn11.

   Evidence Comparative genomics and phylogenetic analysis of PA700/19S subunits across 17 eukaryotic clades

   PMID:25943340

   Open questions at the time

   • phylogenetic inference only — no direct biochemical demonstration of the P. falciparum RPN8 protein in the lid or of the RPN8–Rpn11 dimer
   • no experimental confirmation that RPN8 participates in substrate deubiquitylation in the parasite
2. 2019 Low

   Whether RPN8 contributes catalytic activity to the lid was resolved by domain analysis, which showed its MPN- domain lacks the essential catalytic residues, distinguishing it from the active MPN+ domain of Rpn11 and excluding an intrinsic deNeddylase/metalloprotease function.

   Evidence Bioinformatic domain analysis (PlasmoDB/InterPro JAB1/MPN/MOV34) with chemical probe screens for deNeddylase activity in parasite lysates

   PMID:31658303

   Open questions at the time

   • domain annotation plus negative screen — no direct biochemical assay of purified RPN8 was performed
   • the functional role of the catalytically inactive RPN8 within the lid (e.g. structural or scaffolding contribution) is not defined

• The direct functional role of PF3D7_0912900 in the P. falciparum proteasome, its physical interaction with Rpn11, and any contribution to parasite viability remain uncharacterized in the corpus.
• no direct biochemical or structural evidence for the RPN8–Rpn11 dimer in P. falciparum
• no genetic knockdown/knockout data addressing essentiality
• no defined non-catalytic function for RPN8 within the lid