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54  structures 1046  species 3  interactions 4235  sequences 78  architectures

Family: Alpha_adaptinC2 (PF02883)

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.

Literature references

  1. 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

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.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan E-set (CL0159), which has the following description:

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 218 members:

A2M A2M_BRD A2M_recep Adeno_GP19K AlcCBM31 Alpha-amylase_N Alpha_adaptinC2 Alpha_E2_glycop Arch_flagellin Arylsulfotran_N ASF1_hist_chap ATG19_autophagy BACON Big_1 Big_10 Big_11 Big_2 Big_3 Big_3_2 Big_3_3 Big_3_5 Big_4 Big_5 Big_6 Big_7 Big_8 Big_9 Bile_Hydr_Trans BiPBP_C bMG1 bMG10 bMG3 bMG5 bMG6 BslA BsuPI Cadherin Cadherin-like Cadherin_2 Cadherin_3 Cadherin_4 Cadherin_5 Cadherin_pro CagX Calx-beta Candida_ALS_N CARDB CBM39 CBM_X2 CD45 CelD_N Ceramidse_alk_C CHB_HEX_C CHB_HEX_C_1 ChitinaseA_N ChiW_Ig_like CHU_C Coatamer_beta_C COP-gamma_platf CopC Cyc-maltodext_N Cytomega_US3 DsbC DUF11 DUF1410 DUF1425 DUF1929 DUF2271 DUF3244 DUF3327 DUF3416 DUF3458 DUF3501 DUF3823_C DUF3859 DUF3872 DUF4165 DUF4179 DUF4426 DUF4448 DUF4469 DUF4625 DUF4879 DUF4981 DUF4982 DUF5001 DUF5008 DUF5011 DUF5065 DUF5115 DUF525 DUF5643 DUF916 EB_dh ECD EpoR_lig-bind ERAP1_C EstA_Ig_like Filamin FixG_C Flavi_glycop_C FlgD_ig fn3 Fn3-like fn3_2 fn3_4 fn3_5 fn3_6 FN3_7 Fn3_assoc fn3_PAP GBS_Bsp-like Glucodextran_B Glyco_hydro2_C5 Glyco_hydro_2 Glyco_hydro_61 Gmad2 GMP_PDE_delta GPI-anchored Hanta_G1 He_PIG He_PIG_assoc HECW_N HemeBinding_Shp Hemocyanin_C Herpes_BLLF1 HYR IFNGR1 Ig_GlcNase Ig_mannosidase IL12p40_C Il13Ra_Ig IL17R_fnIII_D1 IL17R_fnIII_D2 IL2RB_N1 IL3Ra_N IL4Ra_N IL6Ra-bind Inhibitor_I42 Inhibitor_I71 Integrin_alpha2 Interfer-bind Invasin_D3 IRK_C IrmA Iron_transport LEA_2 Lep_receptor_Ig LIFR_N Lipase_bact_N LPMO_10 LRR_adjacent LTD Mannosidase_ig MG1 MG2 MG3 MG4 Mo-co_dimer N_BRCA1_IG Na_K-ATPase NEAT Neocarzinostat Neurexophilin NPCBM_assoc PapD_C PBP-Tp47_c Peptidase_C25_C Phlebovirus_G2 PhoD_N PKD PKD_2 PKD_3 Pollen_allerg_1 Pox_vIL-18BP Pur_ac_phosph_N Qn_am_d_aII Qn_am_d_aIII RabGGT_insert Reeler REJ RET_CLD1 RET_CLD3 RET_CLD4 RGI_lyase RHD_dimer Rho_GDI Rib SCAB-Ig SKICH SLAM SoxZ SprB SusE SVA SWM_repeat T2SS-T3SS_pil_N Tafi-CsgC TarS_C1 TcA_RBD TcfC TIG TIG_2 TIG_plexin Tissue_fac Top6b_C Transglut_C Transglut_N TRAP_beta Tuberculin UL16 Velvet WIF Wzt_C Y_Y_Y YBD ZirS_C Zona_pellucida

Alignments

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  Seed
(98)
Full
(4235)
Representative proteomes UniProt
(6387)
NCBI
(9852)
Meta
(8)
RP15
(959)
RP35
(2014)
RP55
(3021)
RP75
(3734)
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  Seed
(98)
Full
(4235)
Representative proteomes UniProt
(6387)
NCBI
(9852)
Meta
(8)
RP15
(959)
RP35
(2014)
RP55
(3021)
RP75
(3734)
Alignment:
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Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(98)
Full
(4235)
Representative proteomes UniProt
(6387)
NCBI
(9852)
Meta
(8)
RP15
(959)
RP35
(2014)
RP55
(3021)
RP75
(3734)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_8859 (release 5.2)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Griffiths-Jones SR , Mian N
Number in seed: 98
Number in full: 4235
Average length of the domain: 109.20 aa
Average identity of full alignment: 19 %
Average coverage of the sequence by the domain: 13.25 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.3 27.3
Trusted cut-off 27.3 27.3
Noise cut-off 27.2 27.2
Model length: 111
Family (HMM) version: 20
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

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Interactions

There are 3 interactions for this family. More...

Alpha_adaptinC2 B2-adapt-app_C Alpha_adaptin_C

Structures

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 54 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 sequence.

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