LIG_AP_GAE_1
ELM server details
ELM
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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(s): LIG_AP_GAE_1
LIG_AP_GAE_1 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: [DE][DES][DEGAS]F[SGAD][DEAP][LVIMFD]
Present in taxon(s): Homo sapiens  Caenorhabditis elegans  Schizosaccharomyces pombe  Eukaryota  Mus musculus  Rattus norvegicus  Saccharomyces cerevisiae  
Not represented in taxon(s):

o See 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 (PMID 12483220). 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 (PMID 14665628, 12808037).

o Selected references

Duncan MC, Costaguta G, Payne GS
Yeast epsin-related proteins required for Golgi-endosome traffic define a gamma-adaptin ear-binding motif.
Nat Cell Biol 2003 Jan;5(1) : 77-81.
PMID: 12483220

o This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.

Biological Process
  vesicle-mediated transport
  Golgi-endosome traffic
Cellular Component
  cytosol
  Golgi apparatus
  Golgi trans-face
  Early endosome
  Clathrin coat
  Clathrin coat of trans-Golgi network vesicle
Molecular Function
  protein binding
  protein domain specific binding

 

o Instances for LIG_AP_GAE_1

SequencePositionSubsequence
(Click for evidence information)		PDBGene NameProtein DescriptionOrganism
YCTB_SCHPO 303-309 PLAFEDDGFGDFQSSAAA - ORFNames=SPCC794.11c; ENTH domain-containing protein C794.11c. Schizosaccharomyces pombe (Fission yeast).
YCTB_SCHPO 341-347 AAKNDDDAFDDFQSAPSA - ORFNames=SPCC794.11c; ENTH domain-containing protein C794.11c. Schizosaccharomyces pombe (Fission yeast).
Q18453_CAEEL 258-264 KKKDDDDGFGDFVSSRSS - Name=rsd-3; ORFNames=C34E11.1; Putative uncharacterized protein rsd-3. Caenorhabditis elegans.
SYNG_HUMAN 773-779 PSGKSDDDFADFHSSKFS - Name=AP1GBP1; Synonyms=SYNG; AP1 subunit gamma-binding protein 1 (Gamma-synergin). Homo sapiens (Human).
RABE1_RAT 436-442 AGNLDESDFGPLVGADSV - Name=Rabep1; Synonyms=Rabpt5, Rabpt5a; Rab GTPase-binding effector protein 1 (Rabaptin-5) (Rabaptin-5alpha). Rattus norvegicus (Rat).
AFTIN_HUMAN 25-31 AEDDDDDEFGEFGGFSEV - Name=AFTPH; Synonyms=AFTH; Aftiphilin. Homo sapiens (Human).
AFTIN_HUMAN 429-435 CNDINEDDFGDFGDFGSA - Name=AFTPH; Synonyms=AFTH; Aftiphilin. Homo sapiens (Human).
VPS3_YEAST 855-861 SENEKDDEFINFTFDEIS - Name=VPS3; Synonyms=VPT17; OrderedLocusNames=YDR495C; ORFNames=D9719.1; Vacuolar protein sorting-associated protein 3 (Vacuolar protein- targeting protein 17). Saccharomyces cerevisiae (Baker's yeast).
ENT3_YEAST 269-275 EEEDDDDEFSEFQSAVPV - Name=ENT3; OrderedLocusNames=YJR125C; ORFNames=J2048; Epsin-3. Saccharomyces cerevisiae (Baker's yeast).
ENT3_YEAST 376-382 TDQDDDDEFGEMHGGAVQ - Name=ENT3; OrderedLocusNames=YJR125C; ORFNames=J2048; Epsin-3. Saccharomyces cerevisiae (Baker's yeast).
ENT5_YEAST 219-225 YDNIDDDEFDADADGFDS - Name=ENT5; OrderedLocusNames=YDR153C; Epsin-5. Saccharomyces cerevisiae (Baker's yeast).
ENT5_YEAST 328-334 NSDDDDDEFGDFQSETSP - Name=ENT5; OrderedLocusNames=YDR153C; Epsin-5. Saccharomyces cerevisiae (Baker's yeast).