Golgi-associated, gamma adaptin ear-containing, ARF-binding protein 2 (GGA2)

Golgi-associated, gamma adaptin ear-containing, ARF-binding protein 2 (GGA2) is a member of the GGA protein family of coat proteins that regulate vesicular trafficking between the trans-Golgi network (TGN) and endosomes[5][1][3]. GGA2 contains an amino-terminal VHS domain that serves as a recognition module for sorting signals, a GAT domain that interacts with ARF GTPases for membrane recruitment, a hinge domain for clathrin binding, and a carboxy-terminal ear (GAE) domain that associates with accessory proteins[3][5]. GGA2 mediates ARF-dependent recruitment of clathrin to the TGN and binds both ubiquitinated proteins and cargoes with an acidic cluster-dileucine motif, contributing to protein sorting, retrograde/anterograde vesicle transport, and lysosomal targeting of select membrane proteins[1][5]. GGA2 directly interacts with the cytoplasmic domain of EGFR and promotes its stability by controlling its lysosomal degradation; depletion of GGA2 leads to enhanced EGFR degradation and reduced cell proliferation[3]. Mutations or altered expression of GGA2 have been implicated in certain cancers and rare lysosomal storage diseases[3][5]. GGA2 is not considered a classical therapeutic target such as a receptor, enzyme, or transporter, but rather an adaptor protein involved in intracellular trafficking pathways.

Other names

ADP-ribosylation factor-binding protein GGA2KIAA1080VEARGamma-adaptin-related protein 2Golgi-localized, gamma ear-containing, ARF-binding protein 2VHS domain and ear domain of gamma-adaptinVHS domain and ear domain-containing protein