FunctionPlays 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 (AC-LL) motif.
Tissue specificityUbiquitously expressed.
Sequence similaritiesBelongs to the GGA protein family. Contains 1 GAE domain. Contains 1 GAT domain. Contains 1 VHS domain.
DomainThe VHS domain functions as a recognition module for sorting signals composed of an acidic cluster followed by two leucines (AC-LL 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 (AC-LL) motifs. The GAE domain binds accessory proteins regulating GGAs function.
Post-translational modificationsPhosphorylated by CK2 and dephosphorylated by PP2A (By similarity). Phosphorylation of GGA3 allows the internal AC-LL motif to bind the VHS domain and to inhibit the recognition of cargo signals. Ubiquitinated.
Pak Y et al. Transport of LAPTM5 to lysosomes requires association with the ubiquitin ligase Nedd4, but not LAPTM5 ubiquitination. J Cell Biol175:631-45 (2006).
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