Vps23

Vps23 is a conserved eukaryotic protein that serves as a subunit of the ESCRT-I (endosomal sorting complex required for transport I) complex. In yeast, the protein is known as Vps23p, and in mammals the functional homolog is TSG101 (tumor susceptibility gene 101). Vps23 participates in the ESCRT pathway that drives sorting of ubiquitinated membrane proteins into intralumenal vesicles of multivesicular bodies (MVBs) and contributes to various membrane remodeling events, including cytokinesis and, in some contexts, viral budding.

Vps23 is part of a four-subunit ESCRT-I complex, typically alongside Vps28, Vps37, and Mvb12. The protein contains a ubiquitin-conjugating enzyme variant (UEV) domain at the N-terminus, which binds ubiquitin and recognizes ubiquitylated cargo. The UEV domain also mediates interactions with proteins bearing ubiquitin-like motifs and, in some viral systems, with late domain motifs such as PTAP, facilitating recruitment of the ESCRT machinery to budding sites.

Localization and function: Vps23 associates with endosomal membranes and helps recruit downstream ESCRT components, coordinating the formation and scission of intralumenal vesicles within MVBs. This process is essential for downregulating many plasma membrane proteins and for proper cell division processes that rely on ESCRT activity.

Significance: Vps23/TSG101 is widely conserved and plays a central role in endosomal sorting and ESCRT-dependent membrane remodeling. In humans, the related protein TSG101 is also studied for its involvement in cancer biology and its exploitation by certain enveloped viruses during budding.