modENCODE |  Help |  blog

Protein Domain : IPR008152

Name  Clathrin adaptor, alpha/beta/gamma-adaptin, appendage, Ig-like subdomain Short Name  Clathrin_a/b/g-adaptin_app_Ig
Type  Domain Description  Proteins synthesized on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. These vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transport []. Clathrin coats contain both clathrin (acts as a scaffold) and adaptor complexes that link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. The two major types of clathrin adaptor complexes are the heterotetrameric adaptor protein (AP) complexes, and the monomeric GGA (Golgi-localising, Gamma-adaptin ear domain homology, ARF-binding proteins) adaptors [, ].AP (adaptor protein) complexes are found in coated vesicles and clathrin-coated pits. AP complexes connect cargo proteins and lipids to clathrin at vesicle budding sites, as well as binding accessory proteins that regulate coat assembly and disassembly (such as AP180, epsins and auxilin). There are different AP complexes in mammals. AP1 is responsible for the transport of lysosomal hydrolases between the TGN and endosomes []. AP2 associates with the plasma membrane and is responsible for endocytosis []. AP3 is responsible for protein trafficking to lysosomes and other related organelles []. AP4 is less well characterised. AP complexes are heterotetramers composed of two large subunits (adaptins), a medium subunit (mu) and a small subunit (sigma). For example, in AP1 these subunits are gamma-1-adaptin, beta-1-adaptin, mu-1 and sigma-1, while in AP2 they are alpha-adaptin, beta-2-adaptin, mu-2 and sigma-2. Each subunit has a specific function. Adaptins recognise and bind to clathrin through their hinge region (clathrin box), and recruit accessory proteins that modulate AP function through their C-terminal ear (appendage) domains. Mu recognises tyrosine-based sorting signals within the cytoplasmic domains of transmembrane cargo proteins []. One function of clathrin and AP2 complex-mediated endocytosis is to regulate the number of GABA(A) receptors available at the cell surface []. GGAs (Golgi-localising, Gamma-adaptin ear domain homology, ARF-binding proteins) are a family of monomeric clathrin adaptor proteins that are conserved from yeasts to humans. GGAs regulate clathrin-mediated the transport of proteins (such as mannose 6-phosphate receptors) from the TGN to endosomes and lysosomes through interactions with TGN-sorting receptors, sometimes in conjunction with AP-1 [, ]. GGAs bind cargo, membranes, clathrin and accessory factors. GGA1, GGA2 and GGA3 all contain a domain homologous to the ear domain of gamma-adaptin. GGAs are composed of a single polypeptide with four domains: an N-terminal VHS (Vps27p/Hrs/Stam) domain, a GAT (GGA and Tom1) domain, a hinge region, and a C-terminal GAE (gamma-adaptin ear) domain. The VHS domain is responsible for endocytosis and signal transduction, recognising transmembrane cargo through the ACLL sequence in the cytoplasmic domains of sorting receptors []. The GAT domain (also found in Tom1 proteins) interacts with ARF (ADP-ribosylation factor) to regulate membrane trafficking [], and with ubiquitin for receptor sorting []. The hinge region contains a clathrin box for recognition and binding to clathrin, similar to that found in AP adaptins. The GAE domain is similar to the AP gamma-adaptin ear domain, and is responsible for the recruitment of accessory proteins that regulate clathrin-mediated endocytosis [].This entry represents a beta-sandwich structural motif found in the appendage (ear) domain of alpha-, beta- and gamma-adaptin from AP clathrin adaptor complexes, and the GAE (gamma-adaptin ear) domain of GGA adaptor proteins. These domains have an immunoglobulin-like beta-sandwich fold containing 7 or 8 strands in 2 beta-sheets in a Greek key topology [, ]. Although these domains share a similar fold, there is little sequence identity between the alpha/beta-adaptins and gamma-adaptin/GAE.More information about these proteins can be found at Protein of the Month: Clathrin [].

Publication Counts Displayer

0 Child Features

0 Contains

2 Cross References

Identifier
Source . Name

Subject . Primary Identifier
PF02883 PFAM IPR008152
SM00809 SMART IPR008152

3 Data Sets

Name URL
TrEMBL data set http://www.ebi.ac.uk/trembl/
InterPro data set  
InterPro GO Annotation data set  

5 Found In

DB identifier Name Short Name Type
IPR017107 Adaptor protein complex AP-1, gamma subunit AP1_complex_gsu Family
IPR008153 Clathrin adaptor, gamma-adaptin, appendage Clathrin_g-adaptin_app Domain
IPR017104 Adaptor protein complex AP-2, alpha subunit AP2_complex_asu Family
IPR013038 Clathrin adaptor, alpha-adaptin, appendage, Ig-like subdomain Clathrin_a-adaptin_app_Ig-like Domain
IPR013037 Clathrin adaptor, beta-adaptin, appendage, Ig-like subdomain Clathrin_b-adaptin_app_Ig-like Domain

3 GO Annotation


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
Clathrin adaptor, alpha/beta/gamma-adaptin, appendage, Ig-like subdomain   GO:0006886 intracellular protein transport
Clathrin adaptor, alpha/beta/gamma-adaptin, appendage, Ig-like subdomain   GO:0016192 vesicle-mediated transport
Clathrin adaptor, alpha/beta/gamma-adaptin, appendage, Ig-like subdomain   GO:0030131 clathrin adaptor complex

3 Ontology Annotations


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
Clathrin adaptor, alpha/beta/gamma-adaptin, appendage, Ig-like subdomain   GO:0006886 intracellular protein transport
Clathrin adaptor, alpha/beta/gamma-adaptin, appendage, Ig-like subdomain   GO:0016192 vesicle-mediated transport
Clathrin adaptor, alpha/beta/gamma-adaptin, appendage, Ig-like subdomain   GO:0030131 clathrin adaptor complex

0 Parent Features

44 Proteins

DB identifier Primary Accession
Organism . Name
FBpp0074558 Q24253 Drosophila melanogaster
FBpp0088945 E8NH12 Drosophila melanogaster
FBpp0088490 P91926 Drosophila melanogaster
FBpp0071298 Q9W329 Drosophila melanogaster
FBpp0301194 Q86B59 Drosophila melanogaster
FBpp0071231 Q9W388 Drosophila melanogaster
FBpp0071230 Q7KVR7 Drosophila melanogaster
FBpp0071232 Q7KVR8 Drosophila melanogaster
FBpp0272566 Q29H04 Drosophila pseudoobscura
FBpp0280380 Q29N38 Drosophila pseudoobscura
FBpp0280960 B5DN54 Drosophila pseudoobscura
FBpp0282999 Q29HG8 Drosophila pseudoobscura
FBpp0164020 B4L4S8 Drosophila mojavensis
FBpp0164750 B4L3F0 Drosophila mojavensis
FBpp0165315 B4L6V2 Drosophila mojavensis
FBpp0167254 B4KFJ2 Drosophila mojavensis
FBpp0229295 B4MET3 Drosophila virilis
FBpp0230163 B4MA28 Drosophila virilis
FBpp0233885 B4M2D2 Drosophila virilis
FBpp0234164 B4LTK9 Drosophila virilis
FBpp0260830 B4PZX8 Drosophila yakuba
FBpp0260880 B4PZ07 Drosophila yakuba
FBpp0261149 B4P2D9 Drosophila yakuba
FBpp0262810 B4PWX6 Drosophila yakuba
A8X7A8_CAEBR A8X7A8 Caenorhabditis briggsae
A8XNZ9_CAEBR A8XNZ9 Caenorhabditis briggsae
A8X9Q7_CAEBR A8X9Q7 Caenorhabditis briggsae
K7GXM2_CAEJA K7GXM2 Caenorhabditis japonica
H2W963_CAEJA H2W963 Caenorhabditis japonica
K7GXM1_CAEJA K7GXM1 Caenorhabditis japonica