TSG101

Tumor susceptibility gene 101, also known as TSG101, is a human is_associated_with::gene that encodes for a cellular protein of the same name.

Function
The protein encoded by this gene belongs to a group of apparently inactive homologs of ubiquitin-conjugating enzymes. The gene product contains a coiled-coil domain that interacts with is_associated_with::stathmin, a cytosolic phosphoprotein implicated in tumorigenesis. The protein may play a role in cell growth and differentiation and act as a negative growth regulator. In vitro steady-state expression of this tumor susceptibility gene appears to be important for maintenance of genomic stability and cell cycle regulation. Mutations and alternative splicing in this gene occur in high frequency in breast cancer and suggest that defects occur during breast cancer tumorigenesis and/or progression.

The main role of ESCRT-I is to recognise ubiquitinated cargo via the UEV is_associated_with::protein domain of the VPS23/TSG101 subunit. The assembly of the ESCRT-I complex is directed by the is_associated_with::C-terminal steadiness box (SB) of VPS23, the N-terminal half of VPS28, and the C-terminal half of VPS37. The structure is primarily composed of three long, parallel is_associated_with::helical hairpins, each corresponding to a different subunit. The additional domains and motifs extending beyond the core serve as gripping tools for ESCRT-I critical functions.

HIV
TSG101 seems to play an important role in the pathogenesis of is_associated_with::HIV. In uninfected cells, TSG101 functions in the biogenesis of the is_associated_with::multivesicular body (MVB), which suggests that HIV may bind TSG101 in order to gain access to the downstream machinery that catalyzes MVB vesicle budding.

Interactions
TSG101 has been shown to interact with:
 * is_associated_with::EP300,
 * HGS,
 * is_associated_with::LRSAM1,
 * is_associated_with::P21,
 * is_associated_with::P53, and
 * is_associated_with::VPS28.

Orthologue, Vps23
In humans, the orthologue of vps23 which has a component of ESCRT-1 is called Tsg101. Mutations in Tsg-101 have been linked to cervical, breast, prostate and gastrointestinal cancers. In molecular biology, vps23 (vacuolar protein sorting) is a is_associated_with::protein domain. Vps proteins are components of the ESCRTs (endosomal sorting complexes required for transport) which are required for protein sorting at the early endosome. More specifically, vps23 is a component of ESCRT-I. The ESCRT complexes form the machinery driving is_associated_with::protein sorting from is_associated_with::endosomes to is_associated_with::lysosomes. ESCRT complexes are central to receptor down-regulation, lysosome biogenesis and is_associated_with::budding of HIV.

Structure
Yeast ESCRT-I consists of three protein subunits, VPS23, VPS28, and VPS37. In humans, ESCRT-I comprises TSG101, VPS28, and one of four potential human VPS37 homologues.