Pathways & interactions
Coatomer/calthrin adaptor appendage, C-terminal subdomain (IPR009028)
Short name: Coatomer/calthrin_app_sub_C
- Coatomer/calthrin adaptor appendage, C-terminal subdomain (IPR009028)
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. This traffic is bidirectional, to ensure that proteins required to form vesicles are recycled. Vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transfer [PMID: 15261670].
Clathrin coats contain both clathrin 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 [PMID: 17449236]. All AP complexes are heterotetramers composed of two large subunits (adaptins), a medium subunit (mu) and a small subunit (sigma). Each subunit has a specific function. Adaptin subunits recognise and bind to clathrin through their hinge region (clathrin box), and recruit accessory proteins that modulate AP function through their C-terminal appendage domains. By contrast, GGAs are monomers composed of four domains, which have functions similar to AP subunits: 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 GAE domain is similar to the AP gamma-adaptin ear domain, being responsible for the recruitment of accessory proteins that regulate clathrin-mediated endocytosis [PMID: 12858162].
While clathrin mediates endocytic protein transport from ER to Golgi, coatomers (COPI, COPII) primarily mediate intra-Golgi transport, as well as the reverse Golgi to ER transport of dilysine-tagged proteins [PMID: 14690497]. Coatomers reversibly associate with Golgi (non-clathrin-coated) vesicles to mediate protein transport and for budding from Golgi membranes [PMID: 17041781]. Coatomer complexes are hetero-oligomers composed of at least an alpha, beta, beta', gamma, delta, epsilon and zeta subunits.
The alpha and beta2 adaptor subunits can each be divided into a trunk domain and the appendage domain (or ear domain), separated by a linker region. Clathrin polymerisation is promoted by its binding to the beta2 appendage and hinge domains. The alpha appendage domain interacts with a number of accessory proteins, including eps15, epsin, amphiphysin, AP180, auxilin, numb, and Dab2, thereby regulating the translocation of these proteins to the bud site.
This entry represents a subdomain of the appendage (ear) domain of alpha- and beta-adaptin from AP clathrin adaptor complexes, and the appendage domain of the gamma subunit of coatomer complexes. These domains have a three-layer arrangement, alpha-beta-alpha, with a bifurcated antiparallel beta-sheet [PMID: 10430869, PMID: 10944104, [PMID: 14690497]. Although the appendage domains from AP adaptins and coatomers share a similar fold, there is little sequence identity between them. However, they also share similar motif-based cargo recognition and accessory factor recruitment mechanisms.
- SSF55711 (SSF55711)