|PROSITE documentation PDOC50180|
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.Last update:
May 2003 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Hirst J. Lui W.W.Y. Bright N.A. Totty N. Seaman M.N.J. Robinson M.S.|
|Title||A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome.|
|Source||J. Cell Biol. 149:67-80(2000).|
|2||Authors||Poussu A. Lohi O. Lehto V.-P.|
|Title||Vear, a novel Golgi-associated protein with VHS and gamma-adaptin 'ear' domains.|
|Source||J. Biol. Chem. 275:7176-7183(2000).|
|3||Authors||Nogi T. Shiba Y. Kawasaki M. Shiba T. Matsugaki N. Igarashi N. Suzuki M. Kato R. Takatsu H. Nakayama K. Wakatsuki S.|
|Title||Structural basis for the accessory protein recruitment by the gamma-adaptin ear domain.|
|Source||Nat. Struct. Biol. 9:527-531(2002).|
|4||Authors||Kent H.M. McMahon H.T. Evans P.R. Benmerah A. Owen D.J.|
|Title||Gamma-adaptin appendage domain: structure and binding site for Eps15 and gamma-synergin.|