Protein Domain : GGA3, GAT domain IPR044111

Type	Domain
Description	ADP-ribosylation factor-binding protein GGA3, also known as golgi-localised gamma ear-containing ARF-binding protein 3, plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. It is required for the lysosomal degradation of BACE (beta-site APP-cleaving enzyme), the protease that initiates the production of beta-amyloid, which causes Alzheimer's disease [ ]. It also plays a key role in GABA transmission, which is important in the regulation of anxiety-like behaviours []. GGA3 mediates the ARF-dependent recruitment of clathrin to the TGN [] and binds ubiquitinated proteins and membrane cargo molecules []. GGA3 belong to the GGA family of proteins, which have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain. The GAT domain is a region of homology of ~130 residues, which is found in eukaryotic GGAs (for Golgi-localized, gamma ear-containing ADP ribosylation factor (ARF)-binding proteins) and vertebrate TOMs (for target of myb). The GAT domain is found in its entirety only in GGAs, although, at the C terminus it shares partial sequence similarity with a short region of TOMs. The GAT domain is found in association with other domains, such as VHS and GAE. The GAT domain of GGAs serves as a molecular anchor of GGA to trans-Golgi network (TGN) membranes via its interaction with the GTP-bound form of a member of the ARF family of small GTPases and can bind specifically to the Rab GTPase effector rabaptin5 and to ubiquitin [ , , , ].The GGA-GAT domain possesses an all α-helical structure, composed of four helices arranged in a somewhat unusual topology, which has been called the helical paper clip. The overall structure shows that the GAT domain has an elongated shape, in which the longest helix participates in two small independent subdomains: an N-terminal helix-loop-helix hook and a C-terminal three-helix bundle. The hook subdomain has been shown to be both necessary and sufficient for ARF-GTP binding and Golgi targeting of GGAs. The N-terminal hook subdomain contains a hydrophobic patch, which is found to interact directly with ARF [ ]. It has been proposed that this interaction might stabilise the hook subdomain [ ]. The C-terminal three-helix bundle is involved in the binding with Rabaptin5 and ubiquitin [].This entry represents the GAT domain found in ADP-ribosylation factor-binding protein GGA3.
Short Name	GAT_GGA3