APPL1 review notes

Deep research via falcon/perplexity-lite failed (no provider keys); research from cached publications and UniProt.

• Rab5 effector on a subpopulation of early endosomes [PMID:15016378 "This pathway operates via APPL1 and APPL2, two Rab5 effectors, which reside on a subpopulation of endosomes."; PMID:21645192 "APPL endosomes are a recently identified subpopulation of early endosomes"]
• BAR-PH dimer binds Rab5 at two sites PMID:17581628
• Phosphoinositide binding PMID:18034774
• AKT2 adaptor in insulin signaling [PMID:10490823 "APPL interacts with the inactive form of AKT2"; PMID:17848569; PMID:26073777 MODY14 LoF variants]
• Adiponectin signaling PMID:19661063
• Nuclear shuttling: NuRD PMID:15016378, Reptin/beta-catenin PMID:19433865, TbetaRI-ICD transport PMID:26583432
• Localization: cytosolic peripheral protein on APPL endosomes "often concentrated at the inner surface of the plasma membrane" PMID:18034774; no TM; NOT surface-exposed. PM annotations kept non-core.
• Protein binding: AKT2 rows -> protein kinase B binding; RAB5A rows -> small GTPase binding; GIPC1/fragmentomics PDZ rows -> PDZ domain binding; rest removed. NEW signaling adaptor activity.