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
  • responsible for interaction with ARF-GTP, UBC & RABEP1
  • required for recruitment to the TGN
  • 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

More general terms

• other protein

Additional terms

• ADP-ribosylation factor [ARF] subfamily protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=23163
• OMIM: https://mirror.omim.org/entry/606006
• UniProt: http://www.uniprot.org/uniprot/Q9NZ52.html