?
 
GAT domain found in eukaryotic GGAs, metazoan Tom1-like proteins, metazoan STAMs, fungal Vps27, and similar proteins The GAT (GGA and Tom1) domain superfamily includes the canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins (GGAs) from eukaryotes, myb protein 1 (Tom1)-like proteins from metazoa, and LAS seventeen-binding protein 5 (Lsb5p)-like proteins from fungi. The canonical GAT domain is a monomeric three-helix bundle that binds ubiquitin. GGAs, also called Golgi-localized gamma-ear-containing Arf-binding proteins, belong to a family of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins that regulate clathrin-mediated trafficking of cargo proteins from the trans-Golgi network (TGN) to endosomes. GGAs play important roles in ubiquitin-dependent sorting of cargo proteins both in biosynthetic and endocytic pathways. Tom1 and its related proteins, Tom1L1 and Tom1L2, form a protein family sharing an N-terminal VHS-domain followed by a GAT domain. Tom1 family proteins bind to ubiquitin, ubiquitinated proteins, and Toll-interacting protein (Tollip) through its GAT domain. They do not associate with either Arf GTPases through its GAT domain nor with acidic cluster-dileucine sequences through its VHS domain. The GAT domain superfamily also includes the non-canonical GAT domain found in several components of the ESCRT-0 complex, including signal transducing adapter molecules (STAMs) and hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) from metazoa, as well as vacuolar protein sorting-associated protein 27 (Vps27) and class E vacuolar protein-sorting machinery protein Hse1 from fungi. Hrs, together with STAM, forms a Hrs/STAM core complex. Vps27, together with Hse1, forms a Vps27/Hse1 core complex. Those complexes consist of two intertwined GAT domains, each consisting of two helices from one subunit, and one from the other subunit. The intertwined GAT heterodimer acts as a scaffold for binding of ubiquitinated cargo proteins and coordinating ubiquitination and deubiquitination reactions that regulate sorting. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",