GGA3

This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) family. This family includes ubiquitous coat proteins that regulate the trafficking of proteins between the trans-Golgi network and the lysosome. These proteins share an amino-terminal VHS domain which mediates sorting of the mannose 6-phosphate receptors at the trans-Golgi network. They also contain a carboxy-terminal region with homology to the ear domain of gamma-adaptins. Multiple alternatively spliced transcript variants have been identified in this gene. [provided by RefSeq, Feb 2010]

Full Name

Golgi Associated, Gamma Adaptin Ear Containing, ARF Binding Protein 3

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:17553422, PubMed:15615712, 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).

Biological Process

Amyloid fibril formation Source: Reactome
Endocytic recycling Source: Ensembl
Golgi to plasma membrane protein transport Source: UniProtKB
Intracellular protein transport Source: UniProtKB
Negative regulation of amyloid-beta formation Source: UniProtKB
Positive regulation of protein catabolic process Source: Ensembl
Protein destabilization Source: UniProtKB
Protein localization to cell surface Source: UniProtKB
Protein targeting to lysosome Source: ARUK-UCL
Regulation of protein stability Source: UniProtKB

Cellular Location

Endosome membrane; Early endosome membrane; Recycling endosome membrane; Trans-Golgi network membrane

Involvement in disease

Isoform GFRalpha4a/Isoform GFRalpha4b: Cell membrane
Isoform GFRalpha4c: Secreted

PTM

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.