ADP-ribosylation factor-binding protein GGA3; Golgi-localized, gamma ear-containing, ARF-binding protein 3 (GGA3 KIAA0154)

Function: - plays a role in protein sorting & trafficking between the trans-Golgi network (TGN) & endosomes - mediates the ARF-dependent recruitment of clathrin to the TGN & binds ubiquitinated proteins & membrane cargo molecules with a cytosolic acidic cluster-dileucine (AC-LL) motif - phosphorylated by CK2 & dephosphorylated by PP2A - phosphorylation of GGA3 allows the internal AC-LL motif to bind the VHS domain & to inhibit the recognition of cargo signals - ubiquitinated - interacts with SORT1, SORL1, LRP3, GGA binding partner (GGABP) & P200 (putative) - interacts with GGA1 & GGA2 - binds to clathrin & activated ARFs - binds RABEP1 & RABGEF1 - interacts with membrane proteins M6PR/CD-MPR, IGF2R/CI-MPR & BACE1 & the accessory proteins SYNRG, EPN4, NECAP1, NECAP2 & AFTPH/aftiphilin - interacts with TSG101 & UBC Structure: - monomer - the VHS domain functions as a recognition module for sorting signals composed of an acidic cluster followed by 2 Leu (AC-LL motif) - the GAT domain a) responsible for interaction with ARF-GTP, UBC & RABEP1 b) required for recruitment to the TGN c) prevents ARF-GTP hydrolysis - the unstructured hinge region contains clathrin-binding & an autoinhibitory (AC-LL) motifs - the GAE domain binds accessory proteins regulating GGAs function - belongs to the GGA protein family - contains 1 GAE domain - contains 1 GAT domain - contains 1 VHS domain Compartment: - Golgi, trans-Golgi network - membrane; peripheral membrane, endosome membrane Alternative splicing: named isoforms=2; long, short Expression: ubiquitously expressed

Properties

SIZE: entity length = 723 aa MW = 78 kD COMPARTMENT: golgi MOTIF: Binds to ARF1 (in long isoform) {1-313} MOTIF: VHS domain {16-146} GAT {171-298} Unstructured hinge {299-593} MOTIF: proline-rich region SITE: 357-360 MOTIF: proline residue (SEVERAL) Autoinhibitory {391-395} serine-rich region {453-457} MOTIF: serine residue (SEVERAL) GAE {594-715}

Database Correlations

OMIM 606006 UniProt Q9NZ52 PFAM correlations Entrez Gene 23163

References

UniProt :accession Q9NZ52