The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Functional site class:
Gamma-adaptin ear interaction motif
Functional site description:
The Gamma-ear interaction motif interacts with gamma-ear domains of adaptor proteins involved in clathrin coated vesicles formation at internal membranes (Golgi/endosomes)
ELM Description:
The ear like domains of GGA 1-3 display significant structure and sequence similarities to that of gamma-adaptins 1 and 2. This conserved domain, referred as gamma adaptin ear (GAE), functions as a platform for recruitment of accessory proteins at the TGN. It interacts with accessory proteins such as Rabaptin-5 and gamma-synergin in mammalian cells and Ent3p and Ent5p in yeast. The interaction is mediated by an acidic Phe based motif: hydrophobic contacts between the Phe residue at position 0 and hydrophobic residues at position +3 and GAE domain are the main determinants of binding and acidic residues preceding this sequence provide a stabilizing effect. The model used for ELM prediction covers most of known true positive instances. However, as recently defined using combinatorial studies, a more comprehensive consensus for GAE binding can be defined where the central Phe residue can be substituted by any aromatic residue while aromatic residues are also functional at the second point of attachment (position +3). This extended pattern is not used presently by ELM because of its massive overprediction.
Pattern Probability: 0.0000053
Present in taxons: Caenorhabditis elegans Eukaryota Homo sapiens Mus musculus Rattus norvegicus Saccharomyces cerevisiae Schizosaccharomyces pombe
Interaction Domain:
Alpha_adaptinC2 (PF02883) Adaptin C-terminal domain (Stochiometry: 1 : 1)
o See 11 Instances for LIG_AP_GAE_1
o Abstract
Clathrin coated vesicles (CCV) are components of endocytosis and trafficking between the Trans Golgi Network (TGN) and endosomes. During CCV formation (less well characterized for internal membranes than for endocytosis), clathrin and clathrin adaptors interact to nucleate coat assembly by binding to appropriate membranes and recruit cargo molecules, clathrin and other coat associated proteins. The clathrin adaptors implicated in CCV formation at the TGN and endosomes are AP-1 and Ggas. AP-1 heterotetrameric complex contains a gamma-adaptin subunit bearing a gamma-ear at its carboxy terminus, while Ggas are monomeric adaptor proteins containing a C-terminal domain related to the ear domain of gamma-adaptin. By analogy with AP-2 (the well characterized adaptor complex involved in endocytic CCV formation) the gamma-ear domain of AP-1 and Ggas probably mediate interactions with accessory proteins during CCV formation.
A novel conserved motif (Acidic Phenylalanine motif) has been described on 2 functionally related Epsin-related proteins (Ent3p and Ent5p) in yeast (S.cerevisiae) . It mediates the interaction between the 2 proteins Ent3p and Ent5p and the gamma-ear domains of Gga2p and AP-1. Ent3p and Ent5p cooperate with Ggas and AP-1 to recruit clathrin and promote the formation of clathrin coats at the Golgi/endosomes (Duncan,2003). A specific role in clathrin localization and assembly on TGN/endosome membranes and in traffic between the TGN and endosomes has been proposed for this motif. The motif is also found in vacuole sorting proteins in yeast (Vps3p and Vps72p), in ENTH containing (uncharacterized) S.pombe and C.elegans proteins, in gamma-synergin and in Rabaptin 5 (human, mouse and rat). Recently, new GAE partners have been identified by combinatorial phage display and in vitro binding studies (Mattera,2004, Lui,2003).
o 1 selected reference:

o 10 GO-Terms:

o 11 Instances for LIG_AP_GAE_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
429 435 TCNDINEDDFGDFGDFGSAS TP 1 Homo sapiens (Human)
25 31 GAEDDDDDEFGEFGGFSEVS TP 1 Homo sapiens (Human)
O35550 Rabep1
436 442 SAGNLDESDFGPLVGADSVS TP 1 Rattus norvegicus (Norway rat)
773 779 TPSGKSDDDFADFHSSKFSS TP 6 Homo sapiens (Human)
Q18453 rsd-3
258 264 SKKKDDDDGFGDFVSSRSSQ TP 1 Caenorhabditis elegans
P78813 SPCC794.11c
341 347 TAAKNDDDAFDDFQSAPSAK TP 1 Schizosaccharomyces pombe (Fission yeast)
P78813 SPCC794.11c
303 309 APLAFEDDGFGDFQSSAAAP TP 1 Schizosaccharomyces pombe (Fission yeast)
Q03769 ENT5
328 334 SNSDDDDDEFGDFQSETSPD TP 8 Saccharomyces cerevisiae (Baker"s yeast)
Q03769 ENT5
219 225 SYDNIDDDEFDADADGFDSE TP 8 Saccharomyces cerevisiae (Baker"s yeast)
P47160 ENT3
376 382 STDQDDDDEFGEMHGGAVQQ TP 8 Saccharomyces cerevisiae (Baker"s yeast)
P47160 ENT3
269 275 DEEEDDDDEFSEFQSAVPVT TP 8 Saccharomyces cerevisiae (Baker"s yeast)
Please cite: ELM 2016-data update and new functionality of the eukaryotic linear motif resource. (PMID:26615199)

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