InterPro domain: IPR008570

This entry represents the Vps25 subunit (vacuolar protein sorting-associated protein 25) of the endosome-associated complex ESCRT-II (Endosomal Sorting Complexes Required for Transport protein II). ESCRT (ESCRT-I, -II, -III) complexes orchestrate efficient sorting of ubiquitinated transmembrane receptors to lysosomes via multivesicular bodies (MVBs) [ 1 ]. ESCRT-II recruits the transport machinery for protein sorting at MVB [ 2 ]. In addition, the human ESCRT-II has been shown to form a complex with RNA polymerase II elongation factor ELL in order to exert transcriptional control activity. ESCRT-II transiently associates with the endosomal membrane and thereby initiates the formation of ESCRT-III, a membrane-associated protein complex that functions immediately downstream of ESCRT-II during sorting of MVB cargo. ESCRT-II in turn functions downstream of ESCRT-I, a protein complex that binds to ubiquitinated endosomal cargo [ 3 ].

ESCRT-II is a trilobal complex composed of two copies of vps25, one copy of vps22 and the C-terminal region of vps36. The crystal structure of vps25 revealed two winged-helix domains, the N-terminal domain of vps25 interacting with vps22 and vps35 [ 4 ].

1. Structural insight into the ESCRT-I/-II link and its role in MVB trafficking. EMBO J. 26, 600-12
2. ESCRT-II, an endosome-associated complex required for protein sorting: crystal structure and interactions with ESCRT-III and membranes. Dev. Cell 7, 559-69
3. Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body. Dev. Cell 3, 283-9
4. Crystal structure of subunit VPS25 of the endosomal trafficking complex ESCRT-II. BMC Struct. Biol. 4, 10