ESCRT-III and Vps4 intralumenal vesicle formation

Multivesicular endosomes form when patches of the limiting endosomal membrane, loaded with ubiquitinated cargo, bud into the lumen and are cut off as intralumenal vesicles, which the lysosome or lytic vacuole later degrades. The scission is done by ESCRT-III: Vps20/CHMP6 nucleates spirals of Snf7/CHMP4, Vps24/CHMP3 and Vps2/CHMP2 cap them, and the Vps4 AAA ATPase remodels and disassembles the polymer. This module is the eukaryote-wide ESCRT-III core, written so that it can be evaluated in any genome.

Eukaryote-wide scope: the ESCRT-III and Vps4 subfamilies used as selectors contain animal, fungal, Dictyostelium and Arabidopsis members, and PAINT places the Vps4 node PTN000553912 at Eukaryota (taxon:2759); the source PAINT rows give no taxon for the ESCRT-III nodes, whose seeds span fungi, animals and Arabidopsis. Read as a satisfiability rule, every part is expected in any eukaryote. ESCRT-III and Vps4 also act at the plasma membrane, the nuclear envelope and the cytokinetic midbody, and archaea use homologs (CdvB, CdvC) for division, so passing this rule shows the membrane-scission machinery is present, not that intralumenal vesicles are made. The subfamily selectors are closed lists read off the reviewed entries in interpro/panther, so a eukaryote whose Snf7/CHMP4, Vps20/CHMP6 or Vps4 falls in a subfamily not listed here fails a required step even if it has the protein; check such a gap against the PANTHER family before reading it as a loss. Not yet modelled: ESCRT-0 (Vps27-Hse1/HRS-STAM, opisthokont), ESCRT-I (Vps23/TSG101, Vps28, Vps37, Mvb12) and ESCRT-II (Vps22, Vps25, Vps36), which recognize ubiquitinated cargo and recruit ESCRT-III; the Bro1/ALIX pathway; and the Vps4 cofactor Vta1/LIP5. Human reviews exist for TSG101, VPS28 and VPS37A-D, so ESCRT-I is the next part to add. The Drosophila-only dmel_escrt_machinery module covers several of these.