Description

IPR021648 is a Vacuolar protein sorting protein 36, GLUE domain.

<p>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 [[cite:PUB00039953]].</p> <p>The multivesicular body (MVB) protein-sorting pathway targets transmembrane proteins either for degradation or for function in the vacuole/lysosomes. The signal for entry into this pathway is monoubiquitination of protein cargo, which results in incorporation of cargo into luminal vesicles at late endosomes. Another crucial player is phosphatidylinositol 3-phosphate (PtdINS(3)P), which is enriched on early endosomes and on the luminal vesicles of MVBs. The ESCRT complexes are critical for MVB budding and sorting of monoubiquitinated cargo into the luminal vesicles. Various Ub-binding domains (UBDs), such as UIM, UEV and NZF are found in such machineries. The Vps 36 subunit of the ESCRT-II trafficking complex binds both phosphoinositides and ubiquitin. All members of the Vps36 family contain a divergent GRAM/PH-like domain and yeast and some other fungi have one or two NZF domains inserted in the GRAM/PH-like domain.</p> <p>The N-terminal region of Vps36 (EAP45) has been named the GLUE (GRAM-like ubiquitin-binding in EAP45) domain. The GLUE domain acts as a central cog driving the endosomal ESCRT machinery, through simultaneous interactions with PtdIns3P-containing membranes, ubiquitin, and ESCRT-I. Like other known ubiquitin-binding domains, the GLUE domain interacts with the hydrophobic surface patch of ubiquitin. The GLUE domain is the first ubiquitin-binding domain shown to bind phosphoinositides, and the ability of the same domain to bind both ubiquitin and a phosphoinositide opens interesting possibilities for coordination of membrane interactions and cargo recognition [[cite:PUB00057959], [cite:PUB00039953], [cite:PUB00040336], [cite:PUB00057960], [cite:PUB00057961]].</p> <p>The GLUE domain has a split PH-domain fold with two curved β sheets and one long α helix. The two sheets (β1/β4 and β5/β7) form a β barrel-like structure, the C-terminal α helix is wedged between the two β sheets, covering a hydrophobic core. The Vps36 GLUE domain binds PtdIns3P via a positively charged lipid binding pocket, delineated by the variable loops β1/β2, β5/β6 and β7/α1, in contrast to the vast majority of characterised PH domains, which use a different lipid binding pocket [[cite:PUB00039953], [cite:PUB00040336]].</p>

This description is obtained from EB-eye REST.

Associated GO terms

GO predictions are based solely on the InterPro-to-GO mappings published by EMBL-EBI, which are in turn based on the mapping of predicted domains to the InterPro dataset. The InterPro-to-GO mapping was last updated on April 27, 2020, while the GO metadata was last updated on April 27, 2020.

Associated Lotus transcripts 4

Co-occuring domains 1

A list of co-occurring predicted domains within the L. japonicus gene space: