Gene interactions and pathways from curated databases and text-mining
Nat Cell Biol 2008, PMID: 18264092

OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD.

Christianson, John C; Shaler, Thomas A; Tyler, Ryan E; Kopito, Ron R

Terminally misfolded or unassembled proteins in the early secretory pathway are degraded by a ubiquitin- and proteasome-dependent process known as ER-associated degradation (ERAD). How substrates of this pathway are recognized within the ER and delivered to the cytoplasmic ubiquitin-conjugating machinery is unknown. We report here that OS-9 and XTP3-B/Erlectin are ER-resident glycoproteins that bind to ERAD substrates and, through the SEL1L adaptor, to the ER-membrane-embedded ubiquitin ligase Hrd1. Both proteins contain conserved mannose 6-phosphate receptor homology (MRH) domains, which are required for interaction with SEL1L, but not with substrate. OS-9 associates with the ER chaperone GRP94 which, together with Hrd1 and SEL1L, is required for the degradation of an ERAD substrate, mutant alpha(1)-antitrypsin. These data suggest that XTP3-B and OS-9 are components of distinct, partially redundant, quality control surveillance pathways that coordinate protein folding with membrane dislocation and ubiquitin conjugation in mammalian cells.

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Text Mining Data

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Manually curated Databases

  • IRef Biogrid Interaction: SERPINA1 — OS9 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: ERLEC1 — SEL1L (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: HSPA5 — OS9 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: ERLEC1 — SYVN1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SERPINA1 — ERLEC1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SYVN1 — OS9 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: OS9 — OS9 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: ERLEC1 — ERLEC1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: HSPA5 — ERLEC1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: HSP90B1 — OS9 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: HSP90B1 — ERLEC1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RPN1 — OS9 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SEL1L — SYVN1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SEL1L — OS9 (physical association, affinity chromatography technology)
  • Reactome Reaction: SYVN1 → ERLEC1 (indirect_complex)
  • Reactome Reaction: OS9 → SHH (direct_complex)
  • Reactome Reaction: OS9 → DERL2 (indirect_complex)
  • Reactome Reaction: OS9 → VCP (reaction)
  • Reactome Reaction: OS9 → VCP (indirect_complex)
  • Reactome Reaction: SHH → ERLEC1 (reaction)
  • Reactome Reaction: SHH → DERL2 (indirect_complex)
  • Reactome Reaction: SYVN1 → ERLEC1 (reaction)
  • Reactome Reaction: SEL1L → SHH (indirect_complex)
  • Reactome Reaction: OS9 → SYVN1 (indirect_complex)
  • Reactome Reaction: SHH → SYVN1 (reaction)
  • Reactome Reaction: DERL2 → ERLEC1 (reaction)
  • Reactome Reaction: OS9 → SEL1L (indirect_complex)
  • Reactome Reaction: OS9 → SEL1L (reaction)
  • Reactome Reaction: SEL1L → ERLEC1 (indirect_complex)
  • Reactome Reaction: OS9 → DERL2 (reaction)
  • Reactome Reaction: DERL2 → ERLEC1 (indirect_complex)
  • Reactome Reaction: SHH → VCP (reaction)
  • Reactome Reaction: SHH → VCP (indirect_complex)
  • Reactome Reaction: SHH → ERLEC1 (direct_complex)
  • Reactome Reaction: OS9 → SHH (reaction)
  • Reactome Reaction: VCP → ERLEC1 (indirect_complex)
  • Reactome Reaction: VCP → ERLEC1 (reaction)
  • Reactome Reaction: SHH → DERL2 (reaction)
  • Reactome Reaction: SEL1L → SHH (reaction)
  • Reactome Reaction: SEL1L → ERLEC1 (reaction)
  • Reactome Reaction: SHH → SYVN1 (indirect_complex)
  • Reactome Reaction: OS9 → SYVN1 (reaction)
In total, 24 gene pairs are associated to this article in curated databases