Protein Domain : GGA3, VHS domain IPR046996

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. This entry represents the VHS domain, which has a superhelical structure similar to the structure of the ARM (Armadillo) repeats and is present at the N-terminal of these proteins. The VHS domain of GGA proteins binds to the acidic-cluster dileucine (DxxLL) motif found on the cytoplasmic tails of cargo proteins trafficked between the Trans-Golgi Network and the endosomal system [, , ].
Short Name	VHS_GGA3