Summary: Adaptin C-terminal domain
The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
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
Internal database links
|SCOOP:||TPK_catalytic Coatamer_beta_C Stn1 BNR_2 DUF4165 AP3B1_C|
External database links
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)|
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Loading domain graphics...
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 76 members:A2M_N Alpha_adaptinC2 Arch_flagellin Big_1 Big_2 Big_3 Big_3_2 Big_3_3 Big_3_4 Big_3_5 Big_4 Big_5 BiPBP_C BsuPI Cadherin Cadherin-like Cadherin_2 Cadherin_3 Cadherin_pro CARDB CBM39 CHB_HEX_C CHB_HEX_C_1 ChitinaseA_N CHU_C Coatamer_beta_C COP-gamma_platf CopC DUF11 DUF2271 DUF3244 DUF4165 DUF4625 DUF5011 DUF916 EpoR_lig-bind Filamin FixG_C FlgD_ig fn3 Fn3-like fn3_2 fn3_4 fn3_5 Fn3_assoc He_PIG HYR IFNGR1 IL17R_fnIII_D2 IL6Ra-bind Integrin_alpha2 Interfer-bind Invasin_D3 LEA_2 MG1 Mo-co_dimer Neurexophilin NPCBM_assoc PhoD_N PKD PKD_2 PKD_3 Pur_ac_phosph_N Qn_am_d_aIII REJ RHD_dimer Rib SoxZ SprB SWM_repeat T2SS-T3SS_pil_N TIG Tissue_fac Transglut_C TRAP_beta Y_Y_Y
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
If you find these logos useful in your own work, please consider citing the following article:
Note: You can also download the data file for the tree.
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:||2419|
|Average length of the domain:||109.40 aa|
|Average identity of full alignment:||20 %|
|Average coverage of the sequence by the domain:||13.62 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||16|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
How the sunburst is generated
Colouring and labels
Anomalies in the taxonomy tree
Missing taxonomic levels
Unmapped species names
Too many species/sequences
The tree shows the occurrence of this domain across different species. More...
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
There are 3 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 48 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.
Loading structure mapping...