GGA3
Domain
The VHS domain functions as a recognition module for sorting signals composed of an acidic cluster followed by two leucines (DXXLL motif).
The GAT domain is responsible for interaction with ARF-GTP, UBC and RABEP1. Required for recruitment to the TGN it prevents ARF-GTP hydrolysis.
The unstructured hinge region contains clathrin-binding and an autoinhibitory (DXXLL) motifs.
The GAE domain binds accessory proteins regulating GGAs function.
Function
Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (DXXLL) motif (PubMed:11301005). Mediates export of the GPCR receptor ADRA2B to the cell surface (PubMed:26811329). nvolved in BACE1 transport and sorting as well as regulation of BACE1 protein levels (PubMed:15615712, PubMed:17553422, PubMed:20484053). Regulates retrograde transport of BACE1 from endosomes to the trans-Golgi network via interaction through the VHS motif and dependent of BACE1 phosphorylation (PubMed:15615712). Modulates BACE1 protein levels independently of the interaction between VHS domain and DXXLL motif through recognition of ubiquitination (PubMed:20484053). Key player in a novel DXXLL-mediated endosomal sorting machinery to the recycling pathway that targets NTRK1 to the plasma membrane (By similarity).
Post-translational modifications
Phosphorylated by CK2 and dephosphorylated by PP2A (By similarity). Phosphorylation of GGA3 allows the internal DXXLL motif to bind the VHS domain and to inhibit the recognition of cargo signals.
Ubiquitinated.
Proteolytically cleaved during apoptosis by CASP3.
Sequence Similarities
Belongs to the GGA protein family.
Tissue Specificity
Ubiquitously expressed.
Cellular localization
- Golgi apparatus
- trans-Golgi network membrane
- Peripheral membrane protein
- Endosome membrane
- Peripheral membrane protein
- Early endosome membrane
- Peripheral membrane protein
- Recycling endosome membrane
- Peripheral membrane protein
Alternative names
KIAA0154, GGA3, ADP-ribosylation factor-binding protein GGA3