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non-canonical GAT domain found in metazoan hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) and similar proteins Hrs, also called protein pp110, is a tyrosine kinase substrate in growth factor-stimulated cells. It is involved in intracellular signal transduction mediated by cytokines and growth factors. Hrs is a component of the ESCRT-0 complex that binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them for further sequential lysosomal sorting/trafficking processes. Members of this family contain a non-canonical GAT (GGA and Tom1) domain consisting of two helices. A canonical GAT domain is a monomeric three-helix bundle that bind to ubiquitin. Hrs, together with another GAT domain-containing protein STAM, forms a Hrs/STAM core complex that consists of two intertwined GAT domains, each consisting of two helices from one subunit, and one from the other subunit. The two GAT domains are connected by a two-stranded coiled-coil. The Hrs/STAM complex, an intertwined GAT heterodimer, is 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.",