ARRDC3 review notes

Sources

• Affinage: trust gates clear.
• Key papers:
• PMID:20559325: ARRDC3 recruits NEDD4 to beta2AR via PPxY.
• PMID:23208550: ARRDCs are secondary adaptors that traffic Nedd4-beta2AR to early endosomes. This contrasts with the first paper and is presented in the adaptor MODIFY.
• PMID:23236378 (full text): alpha-arrestins recruit Nedd4 E3s; ARRDC3 at plasma membrane and endosomes.
• PMID:21982743: mouse knockout; beta-adrenergic receptor binding.
• PMID:20603614: ITGB4.
• PMID:29364502: YAP.
• 67 protein-binding rows were resolved by UniProt batch query.
• NEDD4/NEDD4L/ITCH/WWP1/WWP2 rows → MODIFY to ubiquitin protein ligase binding.
• ADRB2 → beta-2 adrenergic receptor binding.
• ITGB4 → integrin binding.
• All others → REMOVE.
• The IBA node PTN008513893 (endosome, plasma membrane) is seeded only by ARRDC3 itself (Q96B67).

Decisions

• ACCEPT: plasma membrane, endosome, early endosome; beta-3 adrenergic receptor binding.
• MODIFY: molecular adaptor activity (IBA) → ubiquitin-like ligase-substrate adaptor activity, the core MF.
• KEEP_AS_NON_CORE:
• Lysosome, cytoplasm.
• Hippo regulation, positive regulation of ubiquitin-protein transferase activity.
• Cold-induced thermogenesis (mouse ISS/IEA).

2026-10-04 review round (PR #4208)

• Deep-research coverage: cached and cited nine papers (see history). AXL and insulin-receptor cargo claims are not checked (papers not cached).
• Thermogenesis: PMID:28291835 disputes the PMID:21982743 mechanism; the phenotype stands.
• beta2AR: PMID:27226565 contrasts with PMID:20559325.
• Receptor-downregulation BP: no NEW process. ARRDC3 ubiquitinates the sorting factor ALIX rather than PAR1, and β2AR degradation data conflict. Added GO:0016567 instead, after a comparator check: ARRDC1, ARRDC4, ARRB1 and ARRB2 all carry it.