Summary: Clathrin, heavy-chain linker
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Clathrin Edit Wikipedia article
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice that surrounds the vesicle. This is how clathrin gets its name, from the Latin clathratus meaning like a lattice. Coat-proteins, like clathrin, are used to build small vesicles in order to transport molecules within cells. The endocytosis and exocytosis of vesicles allows cells to communicate, to transfer nutrients, to import signaling receptors, to mediate an immune response after sampling the extracellular world, and to clean up the cell debris left by tissue inflammation. The endocytic pathway can be hijacked by viruses and other pathogens in order to gain entry to the cell during infection.
|Clathrin light chain a|
|HGNC||CLTA. HGNC:2090. CLTA.|
|Locus||Chr. 9 q13|
|Clathrin light chain b|
|Locus||Chr. 5 q35|
|Clathrin heavy chain 1|
|Alt. symbols||CHC, CHC17, CLTCL2|
|Locus||Chr. 17 q23.1-qter|
|Clathrin heavy chain 2|
|Locus||Chr. 22 q11.21|
|Clathrin propeller repeat|
Clathrin terminal domain
|SCOPe||1bpo / SUPFAM|
|Clathrin heavy-chain linker|
clathrin heavy chain repeat
|SCOPe||1b89 / SUPFAM|
The clathrin triskelion is composed of three clathrin heavy chains interacting at their C-termini, each ~190 kDa heavy chain has a ~25 kDa light chain tightly bound to it. The three heavy chains provide the structural backbone of the clathrin lattice, and the three light chains are thought to regulate the formation and disassembly of a clathrin lattice. There are two forms of clathrin light chains, designated a and b. The main clathrin heavy chain, located on chromosome 17 in humans, is found in all cells. A second clathrin heavy chain gene, on chromosome 22, is expressed in muscle.
Clathrin heavy chain is often described as a leg, with subdomains, representing the foot (the N-terminal domain), followed by the ankle, distal leg, knee, proximal leg, and trimerization domains. The N-terminal domain consists of a seven-bladed Î²-propeller structure. The other domains form a super-helix of short alpha helices. This was originally determined from the structure of the proximal leg domain that identified and is composed of a smaller structural module referred to as clathrin heavy chain repeat motifs. The light chains bind primarily to the proximal leg portion of the heavy chain with some interaction near the trimerization domain. The Î²-propeller at the 'foot' of clathrin contains multiple binding sites for interaction with other proteins.
When triskelia assemble together in solution, they can interact with enough flexibility to form 6-sided rings (hexagons) that yield a flat lattice, or 5-sided rings (pentagons) that are necessary for curved lattice formation. When many triskelions connect, they can form a basket-like structure. The structure shown, is built of 36 triskelia, one of which is shown in blue. Another common assembly is a truncated icosahedron. To enclose a vesicle, exactly 12 pentagons must be present in the lattice.
In a cell, clathrin triskelion in the cytoplasm binds to an adaptor protein that has bound membrane, linking one of its three feet to the membrane at a time. Clathrin cannot bind to membrane or cargo directly and instead uses adaptor proteins to do this. This triskelion will bind to other membrane-attached triskelia to form a rounded lattice of hexagons and pentagons, reminiscent of the panels on a soccer ball, that pulls the membrane into a bud. By constructing different combinations of 5-sided and 6-sided rings, vesicles of different sizes may assemble. The smallest clathrin cage commonly imaged, called a mini-coat, has 12 pentagons and only two hexagons. Even smaller cages with zero hexagons probably do not form from the native protein, because the feet of the triskelia are too bulky.
Clathrin performs critical roles in shaping rounded vesicles in the cytoplasm for intracellular trafficking. Clathrin-coated vesicles (CCV) selectively sort cargo at the cell membrane, trans-Golgi network, and endosomal compartments for multiple membrane traffic pathways. After a vesicle buds into the cytoplasm, the coat rapidly disassembles, allowing the clathrin to recycle while the vesicle gets transported to a variety of locations.
Adaptor molecules are responsible for self-assembly and recruitment. Two examples of adaptor proteins are AP180 and epsin. AP180 is used in synaptic vesicle formation. It recruits clathrin to membranes and also promotes its polymerization. Epsin also recruits clathrin to membranes and promotes its polymerization, and can help deform the membrane, and thus clathrin-coated vesicles can bud. In a cell, a triskelion floating in the cytoplasm binds to an adaptor protein, linking one of its feet to the membrane at a time. The skelion will bind to other ones attached to the membrane to form a polyhedral lattice, skelion, which pulls the membrane into a bud. The skelion does not bind directly to the membrane, but binds to the adaptor proteins that recognize the molecules on the membrane surface.
Clathrin has another function aside from the coating of organelles. In non-dividing cells, the formation of clathrin-coated vesicles occurs continuously. Formation of clathrin-coated vesicles is shut down in cells undergoing mitosis. During mitosis, clathrin binds to the spindle apparatus, in complex with two other proteins: TACC3 and ch-TOG/CKAP5. Clathrin aids in the congression of chromosomes by stabilizing kinetochore fibers of the mitotic spindle. The amino-terminal domain of the clathrin heavy chain and the TACC domain of TACC3 make the microtubule binding surface for TACC3/ch-TOG/clathrin to bind to the mitotic spindle. The stabilization of kinetochore fibers requires the trimeric structure of clathrin in order to crosslink microtubules.
Clathrin-mediated endocytosis (CME) regulates many cellular physiological processes such as the internalization of growth factors and receptors, entry of pathogens, and synaptic transmission. It is believed that cellular invaders use the nutrient pathway to gain access to a cell's replicating mechanisms. Certain signalling molecules open the nutrients pathway. Two chemical compounds called Pitstop 1 and Pitstop 2, selective clathrin inhibitors, can interfere with the pathogenic activity, and thus protect the cells against invasion. These two compounds selectively block the endocytic ligand association with the clathrin terminal domain in vitro. However, the specificity of these compounds to block clathrin-mediated endocytosis has been questioned.
- Pearse BM (1976). "Clathrin: a unique protein associated with intracellular transfer of membrane by coated vesicles". Proceedings of the National Academy of Sciences of the United States of America. 73 (4): 1255â€“9. doi:10.1073/pnas.73.4.1255. PMC 430241. PMID 1063406.
- "Archived copy". Archived from the original on 2016-01-16. Retrieved 2015-10-07.CS1 maint: archived copy as title (link)
- McMahon HT. "Clathrin and its interactions with AP180". MRC Laboratory of Molecular Biology. Archived from the original on 2009-05-01. Retrieved 2009-04-17.
micrographs of clathrin assembly
- McMahon HT. "Epsin 1 EM gallery". MRC Laboratory of Molecular Biology. Archived from the original on 2009-01-02. Retrieved 2009-04-17.
micrographs of vesicle budding
- Ford MG, Pearse BM, Higgins MK, Vallis Y, Owen DJ, Gibson A, Hopkins CR, Evans PR, McMahon HT (February 2001). "Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 in the nucleation of clathrin lattices on membranes" (PDF). Science. 291 (5506): 1051â€“5. CiteSeerX 10.1.1.407.6006. doi:10.1126/science.291.5506.1051. PMID 11161218. Archived from the original (PDF) on 2008-11-21. Retrieved 2009-04-17.
- Higgins MK, McMahon HT (2002). "Snap-shots of clathrin-mediated endocytosis" (PDF). Trends in Biochemical Sciences. 27 (5): 257â€“63. doi:10.1016/S0968-0004(02)02089-3. PMID 12076538. Archived from the original (PDF) on 2008-11-21. Retrieved 2009-04-17.
- Royle SJ, Bright NA, Lagnado L (2005). "Clathrin is required for the function of the mitotic spindle". Nature. 434 (7037): 1152â€“1157. doi:10.1038/nature03502. PMC 3492753. PMID 15858577.
- Hood FE, Williams SJ, Burgess SG, Richards MW, Roth D, Straube A, Pfuhl M, Bayliss R, Royle SJ (2013). "Coordination of adjacent domains mediates TACC3-ch-TOG-clathrin assembly and mitotic spindle binding". Journal of Cell Biology. 202 (3): 463â€“78. doi:10.1083/jcb.201211127. PMC 3734082. PMID 23918938.
- Role of the Clathrin Terminal Domain in Regulating Coated Pit Dynamics Revealed by Small Molecule Inhibition|Cell, Volume 146, Issue 3, 471-484, 5 August 2011 Abstract Archived 2012-01-19 at the Wayback Machine
- Dutta D, Williamson CD, Cole NB, Donaldson JG (Sep 2012). "Pitstop 2 is a potent inhibitor of clathrin-independent endocytosis". PLoS ONE. 7 (9): e45799. doi:10.1371/journal.pone.0045799. PMC 3448704. PMID 23029248.
- Wakeham DE, Chen CY, Greene B, Hwang PK, Brodsky FM (October 2003). "Clathrin self-assembly involves coordinated weak interactions favorable for cellular regulation". The EMBO Journal. 22 (19): 4980â€“90. doi:10.1093/emboj/cdg511. PMC 204494. PMID 14517237.
- Ford MG, Mills IG, Peter BJ, Vallis Y, Praefcke GJ, Evans PR, McMahon HT (September 2002). "Curvature of clathrin-coated pits driven by epsin". Nature. 419 (6905): 361â€“6. doi:10.1038/nature01020. PMID 12353027.
- Fotin A, Cheng Y, Sliz P, Grigorieff N, Harrison SC, Kirchhausen T, Walz T (2004). "Molecular model for a complete clathrin lattice from electron cryomicroscopy". Nature. 432 (7017): 573â€“9. doi:10.1038/nature03079. PMID 15502812.
- Mousavi SA, MalerÃ¸d L, Berg T, Kjeken R (2004). "Clathrin-dependent endocytosis". Biochemical Journal. 377 (Pt 1): 1â€“16. doi:10.1042/BJ20031000. PMC 1223844. PMID 14505490.
- Smith CJ, Grigorieff N, Pearse BM (September 1998). "Clathrin coats at 21 A resolution: a cellular assembly designed to recycle multiple membrane receptors". The EMBO Journal. 17 (17): 4943â€“53. doi:10.1093/emboj/17.17.4943. PMC 1170823. PMID 9724631. (Model of Clathrin assembly)
- PÃ©rez-GÃ³mez J, Moore I (March 2007). "Plant endocytosis: it is clathrin after all". Current Biology. 17 (6): R217â€“9. doi:10.1016/j.cub.2007.01.045. PMID 17371763. (Review on involvement of clathrin in plant endocytosis)
- Royle SJ, Bright NA, Lagnado L (April 2005). "Clathrin is required for the function of the mitotic spindle". Nature. 434 (7037): 1152â€“7. doi:10.1038/nature03502. PMC 3492753. PMID 15858577.
- Hood FE, Williams SJ, Burgess SG, Richards MW, Roth D, Straube A, Pfuhl M, Bayliss R, Royle SJ (August 2013). "Coordination of adjacent domains mediates TACC3-ch-TOG-clathrin assembly and mitotic spindle binding". J Cell Biol. 202 (3): 463â€“78. doi:10.1083/jcb.201211127. PMC 3734082. PMID 23918938.
- Knuehl C, Chen CY, Manalo V, Hwang PK, Ota N, Brodsky FM (2006). "Novel binding sites on clathrin and adaptors regulate distinct aspects of coat assembly". Traffic (Copenhagen, Denmark). 7 (12): 1688â€“700. doi:10.1111/j.1600-0854.2006.00499.x. PMID 17052248.
- Edeling MA, Smith C, Owen D (2006). "Life of a clathrin coat: insights from clathrin and AP structures". Nature Reviews Molecular Cell Biology. 7 (1): 32â€“44. doi:10.1038/nrm1786. PMID 16493411.
- Dutta D, Williamson CD, Cole NB, Donaldson JG (Sep 2012). "Pitstop 2 is a potent inhibitor of clathrin-independent endocytosis". PLoS ONE. 7 (9): e45799. doi:10.1371/journal.pone.0045799. PMC 3448704. PMID 23029248.
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.
Clathrin, heavy-chain linker Provide feedback
Members of this family adopt a structure consisting of alpha-alpha superhelix. They are predominantly found in clathrin, where they act as a heavy-chain linker domain .
Miele AE, Watson PJ, Evans PR, Traub LM, Owen DJ; , Nat Struct Mol Biol. 2004;11:242-248.: Two distinct interaction motifs in amphiphysin bind two independent sites on the clathrin terminal domain beta-propeller. PUBMED:14981508 EPMC:14981508
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR015348
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].
Clathrin is a trimer composed of three heavy chains and three light chains, each monomer projecting outwards like a leg; this three-legged structure is known as a triskelion [PUBMED:15752139, PUBMED:16806884]. The heavy chains form the legs, their N-terminal beta-propeller regions extending outwards, while their C-terminal alpha-alpha-superhelical regions form the central hub of the triskelion. Peptide motifs can bind between the beta-propeller blades. The light chains appear to have a regulatory role, and may help orient the assembly and disassembly of clathrin coats as they interact with hsc70 uncoating ATPase [PUBMED:16734666]. Clathrin triskelia self-polymerise into a curved lattice by twisting individual legs together. The clathrin lattice forms around a vesicle as it buds from the TGN, plasma membrane or endosomes, acting to stabilise the vesicle and facilitate the budding process [PUBMED:15261670]. The multiple blades created when the triskelia polymerise are involved in multiple protein interactions, enabling the recruitment of different cargo adaptors and membrane attachment proteins [PUBMED:16699812].
This entry represents the core motif for the alpha-helical zigzag linker region connecting the conserved N-terminal beta-propeller region to the C-terminal alpha-alpha-superhelical region in clathrin heavy chains [PUBMED:9827808].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||clathrin coat of coated pit (GO:0030132)|
|clathrin coat of trans-Golgi network vesicle (GO:0030130)|
|Molecular function||structural molecule activity (GO:0005198)|
|Biological process||intracellular protein transport (GO:0006886)|
|vesicle-mediated transport (GO:0016192)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
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Tetratricopeptide-like repeats are found in a numerous and diverse proteins involved in such functions as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neurogenesis and protein folding.
The clan contains the following 157 members:Adaptin_N Alkyl_sulf_dimr ANAPC3 ANAPC5 ANAPC8 API5 Arm Arm_2 Arm_3 Atx10homo_assoc B56 BAF250_C BTAD CAS_CSE1 ChAPs CHIP_TPR_N CID CLASP_N Clathrin Clathrin-link Clathrin_H_link Clathrin_propel Cnd1 Cnd3 Coatomer_E Cohesin_HEAT Cohesin_load ComR_TPR COPI_C CPL CRM1_C Cse1 CTK3 DHR-2 DNA_alkylation Drf_FH3 Drf_GBD DUF1822 DUF2019 DUF2225 DUF3385 DUF3458_C DUF3808 DUF3856 DUF4042 DUF5691 DUF924 EST1 EST1_DNA_bind FAT Fis1_TPR_C Fis1_TPR_N Foie-gras_1 GUN4_N HAT HEAT HEAT_2 HEAT_EZ HEAT_PBS HemY_N HrpB1_HrpK HSM3_N IBB IBN_N IFRD Importin_rep_3 Importin_rep_6 KAP Leuk-A4-hydro_C LRV LRV_FeS MA3 MIF4G MIF4G_like MIF4G_like_2 MMS19_C Mo25 MRP-S27 Mtf2 NARP1 Neurochondrin Nipped-B_C Nro1 NSF Paf67 ParcG PC_rep PHAT PI3Ka PknG_TPR PPP5 PPR PPR_1 PPR_2 PPR_3 PPR_long PPTA Proteasom_PSMB PUF Rab5-bind Rapsyn_N RIX1 RNPP_C RPM2 RPN7 Sel1 SHNi-TPR SNAP SPO22 SRP_TPR_like ST7 Suf SusD-like SusD-like_2 SusD-like_3 SusD_RagB SYCP2_ARLD TAF6_C TAL_effector TAtT Tcf25 TIP120 TOM20_plant TPR_1 TPR_10 TPR_11 TPR_12 TPR_14 TPR_15 TPR_16 TPR_17 TPR_18 TPR_19 TPR_2 TPR_20 TPR_21 TPR_3 TPR_4 TPR_5 TPR_6 TPR_7 TPR_8 TPR_9 TPR_MalT UNC45-central Upf2 V-ATPase_H_C V-ATPase_H_N Vac14_Fab1_bd Vitellogenin_N Vps39_1 W2 Wzy_C_2 Xpo1 YcaO_C YfiO Zmiz1_N
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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
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 UniProtKB sequence database using the family HMM
- 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:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
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.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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...
If you find these logos useful in your own work, please consider citing the following article:
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.
|Number in seed:||49|
|Number in full:||1658|
|Average length of the domain:||23.90 aa|
|Average identity of full alignment:||55 %|
|Average coverage of the sequence by the domain:||1.52 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||11|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
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- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
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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 Clathrin-link domain has been found. There are 61 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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