Summary: Adaptin C-terminal domain
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Adaptin C-terminal domain Provide feedback
Alpha adaptin is a heterotetramer which regulates clathrin-bud formation. The carboxyl-terminal appendage of the alpha subunit regulates translocation of endocytic accessory proteins to the bud site. This ig-fold domain is found in alpha, beta and gamma adaptins.
Traub LM, Downs MA, Westrich JL, Fremont DH; , Proc Natl Acad Sci U S A 1999;96:8907-8912.: Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly PUBMED:10430869 EPMC:10430869
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This tab holds annotation information from the InterPro database.
InterPro entry IPR008152
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 [PUBMED:15261670]. 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 [PUBMED:17449236, PUBMED:11598180].
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 [PUBMED:15107467]. AP2 associates with the plasma membrane and is responsible for endocytosis [PUBMED:12952931]. AP3 is responsible for protein trafficking to lysosomes and other related organelles [PUBMED:16542748]. 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 [PUBMED:11080148]. One function of clathrin and AP2 complex-mediated endocytosis is to regulate the number of GABA(A) receptors available at the cell surface [PUBMED:17254016].
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 [PUBMED:14973137, PUBMED:14745135]. 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 [PUBMED:11859376]. The GAT domain (also found in Tom1 proteins) interacts with ARF (ADP-ribosylation factor) to regulate membrane trafficking [PUBMED:16413283], and with ubiquitin for receptor sorting [PUBMED:15966896]. 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 [PUBMED:12858162].
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 [PUBMED:12042876, PUBMED:12808037]. 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 [PUBMED:].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||clathrin adaptor complex (GO:0030131)|
|Biological process||intracellular protein transport (GO:0006886)|
|vesicle-mediated transport (GO:0016192)|
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This clan includes a diverse range of domains that have an Ig-like fold and appear to be distantly related to each other. The clan includes: PKD domains, cadherins and several families of bacterial Ig-like domains as well as viral tail fibre proteins. it also includes several Fibronectin type III domain-containing families.
The clan contains the following 63 members:A2M_N Alpha_adaptinC2 Big_1 Big_2 Big_3 Big_3_2 Big_3_3 Big_3_4 Big_4 Big_5 BiPBP_C BsuPI Cadherin Cadherin-like Cadherin_2 Cadherin_pro CARDB CHB_HEX_C CHB_HEX_C_1 ChitinaseA_N CHU_C Coatamer_beta_C COP-gamma_platf CopC DUF1034 DUF11 DUF1973 DUF2271 DUF4165 DUF4625 DUF916 EpoR_lig-bind Filamin FixG_C FlgD_ig fn3 Fn3_assoc He_PIG HYR IFNGR1 IL6Ra-bind Integrin_alpha2 Interfer-bind Invasin_D3 MG1 Mo-co_dimer Neurexophilin NPCBM_assoc PapD_N PKD PPC Qn_am_d_aIII REJ Rib SoxZ SprB SWM_repeat T2SS-T3SS_pil_N TIG Tissue_fac Transglut_C TRAP_beta Y_Y_Y
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Curation and family details
|Seed source:||Pfam-B_8859 (release 5.2)|
|Author:||Bateman A, Griffiths-Jones SR, Mian N|
|Number in seed:||102|
|Number in full:||1431|
|Average length of the domain:||109.40 aa|
|Average identity of full alignment:||19 %|
|Average coverage of the sequence by the domain:||13.69 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Alpha_adaptinC2 domain has been found. There are 45 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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