Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
68  structures 1468  species 0  interactions 10424  sequences 198  architectures

Family: Adap_comp_sub (PF00928)

Summary: Adaptor complexes medium subunit family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Adaptor complexes medium subunit domain". More...

Adaptor complexes medium subunit domain Edit Wikipedia article

PDB 1h6e EBI.jpg
mu2 adaptin subunit (ap50) of ap2 adaptor (second domain), complexed with ctla-4 internalization peptide ttgvyvkmppt
Symbol Adap_comp_sub
Pfam PF00928
Pfam clan CL0448
InterPro IPR008968
SCOP 1bxx

In molecular biology, the adaptor complexes medium subunit domain is a protein domain found at the C-terminus of the mu subunit from various clathrin adaptor protein complexes (AP1, AP2, AP3, AP4 and AP5)[1] and muniscins. The C-terminal domain has an immunoglobulin-like beta-sandwich fold consisting of 9 strands in 2 sheets with a Greek key topology, similar to that found in cytochrome f and certain transcription factors.[2] The mu subunit regulates the coupling of clathrin lattices with particular membrane proteins by self-phosphorylation via a mechanism that is still unclear.[3] The mu subunit possesses a highly conserved N-terminal domain of around 230 amino acids, which may be the region of interaction with other AP proteins; a linker region of between 10 and 42 amino acids; and a less well-conserved C-terminal domain of around 190 amino acids, which may be the site of specific interaction with the protein being transported in the vesicle.[3]


  1. ^ Mattera R, Guardia CM, Sidhu SS, Bonifacino JS (2015). "Bivalent Motif-Ear Interactions Mediate the Association of the Accessory Protein Tepsin with the AP-4 Adaptor Complex". The Journal of Biological Chemistry. 290 (52): 30736–49. doi:10.1074/jbc.M115.683409. PMC 4692204Freely accessible. PMID 26542808. 
  2. ^ Follows ER, McPheat JC, Minshull C, Moore NC, Pauptit RA, Rowsell S, Stacey CL, Stanway JJ, Taylor IW, Abbott WM (October 2001). "Study of the interaction of the medium chain mu 2 subunit of the clathrin-associated adapter protein complex 2 with cytotoxic T-lymphocyte antigen 4 and CD28". Biochem. J. 359 (Pt 2): 427–34. doi:10.1042/0264-6021:3590427. PMC 1222163Freely accessible. PMID 11583591. 
  3. ^ a b Nakayama Y, Goebl M, O'Brine Greco B, Lemmon S, Pingchang Chow E, Kirchhausen T (December 1991). "The medium chains of the mammalian clathrin-associated proteins have a homolog in yeast". Eur. J. Biochem. 202 (2): 569–74. doi:10.1111/j.1432-1033.1991.tb16409.x. PMID 1761056. 

External links

This article incorporates text from the public domain Pfam and InterPro IPR008968

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

Adaptor complexes medium subunit family Provide feedback

This family also contains members which are coatomer subunits.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR028565

The mu homology domain (MHD) is an ~280 residue protein-protein interaction module, which is found in endocytotic proteins involved in clathrin-mediated endocytosis [ PUBMED:11381094 , PUBMED:11454741 , PUBMED:14726597 , PUBMED:19713939 ]:

  • Mu subunits of adaptor protein (AP) complexes, AP-1, AP-2, AP-3, and AP-4.
  • Proteins of the stonin family.
  • Proteins of the muniscin family: Syp1, FCHO1/2 and SGIP1.

The MHD domain has an elongated, banana-shaped, all beta-sheet structure. It can be considered as two beta-sandwich subdomains (A and B), with subdomain B inserted between strands 6 and 15 of subdomain A, and joined edge to edge such that the convex surface is a continuous nine-stranded mixed beta-sheet that runs the whole length of the molecule. The tyrosine based signal binds to a site on the surface of two parallel beta-sheet strands (beta1 and beta16) in subdomain A [ PUBMED:19713939 , PUBMED:9812899 ].

Domain organisation

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

Loading domain graphics...

Pfam Clan

This family is a member of clan Cargo_bd_muHD (CL0448), which has the following description:

Internalisation of diverse transmembrane cargos from the plasma membrane requires a similarly diverse array of specialized adaptors, this domain is the binding domain of these endocytioc adaptors. The muHD binds directly to the cytosolic tail of the Mid2 (for the transmembrane stress sensor protein Mid2) cargo protein and mediates Mid2 internalization [1]. These are all-beta proteins.

The clan contains the following 2 members:

Adap_comp_sub muHD


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
Jalview View  View  View  View  View  View  View 
HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

Download options

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.

Representative proteomes UniProt
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


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.

Note: You can also download the data file for the tree.

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_1007 (release 3.0)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Finn RD , Bateman A , Coggill P
Number in seed: 46
Number in full: 10424
Average length of the domain: 258.50 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 53.33 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 31.6 31.6
Trusted cut-off 31.7 31.6
Noise cut-off 31.5 31.5
Model length: 264
Family (HMM) version: 23
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

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


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.


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 Adap_comp_sub domain has been found. There are 68 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.

Loading structure mapping...