• adaptor of E3 ubiquitin ligase complex HRD1 in ER membrane, HRD3 in yeast, SEL1L in metazoans; recruits misfolded proteins to E3 ligase and also recruits other adaptors, such as lectins Yos9p/OS-9/XTP3-B to E3 complex
  • contain single transmembrane domain, which in the case of Hrd3p is dispensable for function (Gardner et al., 2000; J Cell Biol)
  • large luminal domain composed of multiple tetratricopeptide repeats (TPRs) thought to facilitate protein-protein interactions (Gauss et al., 2006; Nat Cell Biol)
  • Hrd3p forms a stoichiometric complex with Hrd1p and inhibits its auto-ubiquitylation (which would lead to Hrd1p degradation) ==> dual activity of Hrd3p as adaptor and regulator ensures that Hrd1p is active only in the presence of controlled substrate delivery
  • in mammalian HRD1 it seems to be the other way round: HRD1 appears to stabilize SEL1L