Molecular phylogeny of a RING E3 ubiquitin ligase, conserved in eukaryotic cells and dominated by homologous components, the muskelin/RanBPM/CTLH complex.

摘要: Ubiquitination is an essential post-translational modification that regulates signalling and protein turnover in eukaryotic cells. Specificity of ubiquitination driven by ubiquitin E3 ligases, many which remain poorly understood. One such the mammalian muskelin/RanBP9/CTLH complex includes eight proteins, five (RanBP9/RanBPM, TWA1, MAEA, Rmnd5 muskelin), share striking similarities domain architecture have been implicated regulation cell organisation. In budding yeast, homologous GID acts to down-regulate gluconeogenesis. both complexes, Rmnd5/GID2 corresponds a RING ligase. To better understand this ligase system, we conducted molecular phylogenetic sequence analyses related components. Rmnd5, MAEA WDR26 are conserved throughout all supergroups, albeit was not identified Rhizaria. RanBPM absent from Excavates some sub-lineages. Armc8 c17orf39 were represented across unikonts but bikonts only Viridiplantae O. trifallax within alveolates. Muskelin present Opisthokonts. Phylogenetic shared LisH CTLH domains RanBPM, revealed closer relationships profiles residues between, respectively, TWA1. also presence conserved, variant domains. Examination how N- or C-terminal deletions alter sub-cellular localisation each cells distinct contributions folding/stability. conclusion, components except muskelin inferred last common ancestor. Diversification different lineages may result apparently fast evolution differing requirements for WDR26, c17orf39, origin opisthokonts as RanBPM-binding protein.