PROSITE documentation PDOC50180

Gamma-adaptin ear (GAE) domain profile

The adaptor proteins AP-1 and GGA (Golgi-localized, γ ear-containing, ADP-ribosylation factor (ARF)-binding proteins) regulate membrane traffic between the trans-Golgi network (TGN) and endosome/lysosomes through ARF-regulated membrane association, recognition of sorting signals, and recruitment of clathrin and accessory proteins. The γ-adaptin ear (GAE) domain is a C-terminal appendage or ear of about 120 residues, which is found in γ-adaptins, the heavy subunits of the AP-1 complex, and in GGAs. The GAE domain, which is found in associated with other domains such as VHS (see <PDOC50179>), coiled-coils and GAT, is involved in the recruitment of accessory proteins, such as γ-synergin, Rababptin-5, Eps15 and cyclin G-associated kinase, which modulate the functions of GAE domain containing proteins in the membrane trafficking events [1,2,3,4].

The resolution of the 3D-structure of the human γ-adaptin GAE domain shows that it forms an immunoglobulin-like β-sandwich fold composed of eight β-strands with two short α-helices (see <PDB:1IU1>). The topology of the entire GAE domain is similar to those of the N-terminal subdomains in the α- and β-adaptin ear domains of the AP-2 complex. However, the GAE domain has very low sequence identity and homology to the N-terminal immunoglobulin-like subdomains of the α and β ear domains. The binding site for the accessory proteins has been located to a shallow hydrophobic trough surrounded by charged (mainly basic) residues [3,4].

The profile we developed covers the entire GAE domain.