InterPro domain: IPR037855

Vps36 is a subunit of ESCRT-II, a protein complex involved in driving protein sorting from endosomes to lysosomes. The GLUE domain of Vps36 allows for a tight interaction to occur between the protein and Vps28, a subunit of ESCRT-I. This interaction is critical for ubiquitinated cargo progression from early to late endosomes [ 1 ].

The multivesicular body (MVB) protein-sorting pathway targets transmembraneproteins either for degradation or for function in the vacuole/lysosomes. Thesignal for entry into this pathway is monoubiquitination of protein cargo,which results in incorporation of cargo into luminal vesicles at lateendosomes. Another crucial player is phosphatidylinositol 3-phosphate(PtdINS(3)P), which is enriched on early endosomes and on the luminal vesiclesof MVBs. ESCRT (endosomal sorting complex required for transport)-I, -II and -III complexes are critical for MVB budding and sorting ofmonoubiquitinated cargo into the luminal vesicles [ 2 ]. Various Ub-binding domains(UBDs), such as UIM, UEV and NZF are found in suchmachineries [ 3 , 3 ].

The Vps 36 subunit of the ESCRT-II trafficking complex binds bothphosphoinositides and ubiquitin. All members of the Vps36 family contain adivergent GRAM/PH-like domain; yeast and some other fungi have one or twoNZF domains inserted in the GRAM/PH-like domain [ 4 , 4 ].

1. ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes. Cell 125, 99-111
2. The emerging shape of the ESCRT machinery. Nat. Rev. Mol. Cell Biol. 8, 355-68
3. Structural insight into the ESCRT-I/-II link and its role in MVB trafficking. EMBO J. 26, 600-12