{PDOC50180} {PS50180; GAE} {BEGIN} ****************************************** * Gamma-adaptin ear (GAE) domain profile * ****************************************** The adaptor proteins AP-1 and GGA (Golgi-localized, gamma 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 gamma-adaptin ear (GAE) domain is a C- terminal appendage or ear of about 120 residues, which is found in gamma- 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 ), coiled-coils and GAT, is involved in the recruitment of accessory proteins, such as gamma-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 gamma-adaptin GAE domain shows that it forms an immunoglobulin-like beta-sandwich fold composed of eight beta-strands with two short alpha-helices (see ). The topology of the entire GAE domain is similar to those of the N-terminal subdomains in the alpha- and beta-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 alpha and beta 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. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: May 2003 / First entry. [ 1] Hirst J., Lui W.W.Y., Bright N.A., Totty N., Seaman M.N.J., Robinson M.S. "A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome." J. Cell Biol. 149:67-80(2000). PubMed=10747088 [ 2] Poussu A., Lohi O., Lehto V.-P. "Vear, a novel Golgi-associated protein with VHS and gamma-adaptin 'ear' domains." J. Biol. Chem. 275:7176-7183(2000). PubMed=10702286 [ 3] Nogi T., Shiba Y., Kawasaki M., Shiba T., Matsugaki N., Igarashi N., Suzuki M., Kato R., Takatsu H., Nakayama K., Wakatsuki S. "Structural basis for the accessory protein recruitment by the gamma-adaptin ear domain." Nat. Struct. Biol. 9:527-531(2002). PubMed=12042876; DOI=10.1038/nsb808 [ 4] Kent H.M., McMahon H.T., Evans P.R., Benmerah A., Owen D.J. "Gamma-adaptin appendage domain: structure and binding site for Eps15 and gamma-synergin." Structure 10:1139-1148(2002). PubMed=12176391 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}