Summary: Integrin beta tail domain
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 "Integrin". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at email@example.com and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Integrin Edit Wikipedia article
|Integrin alphavbeta3 extracellular domains|
Structure of the extracellular segment of integrin alpha Vbeta3.
|Integrin alpha cytoplasmic region|
Structure of chaperone protein PAPD.
|Integrin, beta chain|
|Integrin beta 7 cytoplasmic domain: complex with filamin|
crystal structure of the filamin a repeat 21 complexed with the integrin beta7 cytoplasmic tail peptide
Integrins are transmembrane receptors that mediate the attachment between a cell and its surroundings, such as other cells or the extracellular matrix (ECM). In signal transduction, integrins pass information about the chemical composition and mechanical status of the ECM into the cell. Therefore, in addition to transmitting mechanical forces across otherwise vulnerable membranes, they are involved in cell signaling and the regulation of cell cycle, shape, and motility.
Typically, receptors inform a cell of the molecules in its environment and the cell responds. Not only do integrins perform this outside-in signaling, but they also operate an inside-out mode. Thus, they transduce information from the ECM to the cell as well as reveal the status of the cell to the outside, allowing rapid and flexible responses to changes in the environment, for example to allow blood coagulation by platelets.
There are many types of integrin, and many cells have multiple types on their surface. Integrins are of vital importance to all animals and have been found in all animals investigated, from sponges to mammals. Integrins have been extensively studied in humans.
Integrins work alongside other proteins such as cadherins, immunoglobulin superfamily cell adhesion molecules, selectins and syndecans to mediate cell–cell and cell–matrix interaction and communication. Integrins bind cell surface and ECM components such as fibronectin, vitronectin, collagen, and laminin.
Integrins are obligate heterodimers containing two distinct chains, called the α (alpha) and β (beta) subunits. In mammals, eighteen α and eight β subunits have been characterized, whereas the Drosophila genome encodes only five α and two β subunits, and Caenorhabditis nematodes possess genes for two α subunits and one β. The α and β subunits each penetrate the plasma membrane and possess small cytoplasmic domains.
In addition, variants of some of the subunits are formed by differential splicing; for example four variants of the beta-1 subunit exist. Through different combinations of the α and β subunits, some 24 unique integrins are generated, although the number varies according to different studies.
Integrin subunits span the plasma membrane and in general have short cytoplasmic domains of about 40–70 amino acids. The exception is the beta-4 subunit, which has a cytoplasmic domain of 1088 amino acids, one of the largest known cytoplasmic domains of any membrane protein. Outside the cell plasma membrane, the α and β chains lie close together along a length of about 23 nm; the final 5 nm N-termini of each chain forms a ligand-binding region for the extracellular matrix (ECM).
The molecular mass of the integrin subunits can vary from 90 kDa to 160 kDa. Beta subunits have four cysteine-rich repeated sequences. Both α and β subunits bind several divalent cations. The role of divalent cations in the α subunit is unknown, but may stabilize the folds of the protein. The cations in the β subunits are more interesting: they are directly involved in coordinating at least some of the ligands that integrins bind.
There are various ways of categorizing the integrins. For example, a subset of the α chains has an additional structural element (or "domain") inserted toward the N-terminal, the alpha-A domain (so called because it has a similar structure to the A-domains found in the protein von Willebrand factor; it is also termed the α-I domain). Integrins carrying this domain either bind to collagens (e.g. integrins α1 β1, and α2 β1), or act as cell-cell adhesion molecules (integrins of the β2 family). This α-I domain is the binding site for ligands of such integrins. Those integrins that don't carry this inserted domain also have an A-domain in their ligand binding site, but this A-domain is found on the β subunit.
In both cases, the A-domains carry up to three divalent cation binding sites. One is permanently occupied in physiological concentrations of divalent cations, and carries either a calcium or magnesium ion, the principal divalent cations in blood at median concentrations of 1.4 mM (calcium) and 0.8 mM (magnesium). The other two sites become occupied by cations when ligands bind—at least for those ligands involving an acidic amino acid in their interaction sites. An acidic amino acid features in the integrin-interaction site of many ECM proteins, for example as part of the amino acid sequence Arginine-Glycine-Aspartic acid ("RGD" in the one-letter amino acid code).
 High resolution structure
Despite many years of effort, discovering the high-resolution structure of integrins proved to be challenging: membrane proteins are classically difficult to purify, and integrins are also large, complex and linked to many sugar trees ("highly glycosylated"). Low-resolution images of detergent extracts of intact integrin GPIIbIIIa, obtained using electron microscopy, and even data from indirect techniques that investigate the solution properties of integrins using ultracentrifugation and light scattering, were combined with fragmentary high-resolution crystallographic or NMR data from single or paired domains of single integrin chains, and molecular models postulated for the rest of the chains.
Despite these wide-ranging efforts, the X-ray crystal structure obtained for the complete extracellular region of one integrin, αvβ3, was a surprise. It showed the molecule to be folded into an inverted V-shape that potentially brings the ligand-binding sites close to the cell membrane. Perhaps more importantly, the crystal structure was also obtained for the same integrin bound to a small ligand containing the RGD-sequence, the drug cilengitide. As detailed above, this finally revealed why divalent cations (in the A-domains) are critical for RGD-ligand binding to integrins. The interaction of such sequences with integrins is believed to be a primary switch by which ECM exerts its effects on cell behaviour.
The structure poses many questions, especially regarding ligand binding and signal transduction. The ligand binding site is directed towards the C-terminal of the integrin, the region where the molecule emerges from the cell membrane. If it emerges orthogonally from the membrane, the ligand binding site would apparently be obstructed, especially as integrin ligands are typically massive and well cross-linked components of the ECM. In fact, little is known about the angle that membrane proteins subtend to the plane of the membrane; this is a problem difficult to address with available technologies. The default assumption is that they emerge rather like little lollipops, but the evidence for this sweet supposition is noticeable by its absence. The integrin structure has drawn attention to this problem, which may have general implications for how membrane proteins work. It appears that the integrin transmembrane helices are tilted (see "Activation" below) which hints that the extracellular chains may also not be orthogonal with respect to the membrane surface.
Although the crystal structure changed surprisingly little after binding to cilengitide, the current hypothesis is that integrin function involves changes in shape to move the ligand-binding site into a more accessible position, away from the cell surface, and this shape change also triggers intracellular signaling. There is a wide body of cell-biological and biochemical literature that supports this view. Perhaps the most convincing evidence involves the use of antibodies that only recognize integrins when they have bound to their ligands, or are activated. As the "footprint" that an antibody makes on its binding target is roughly a circle about 3 nm in diameter, the resolution of this technique is low. Nevertheless, these so-called LIBS (Ligand-Induced-Binding-Sites) antibodies unequivocally show that dramatic changes in integrin shape routinely occur. However, how the changes detected with antibodies look like on the structure is still unknown.
When released into the cell membrane, newly synthesized integrin dimers are speculated to be found in the same "bent" conformation revealed by the structural studies described above. One school of thought claims that this bent form prevents them from interacting with their ligands, although bent forms can predominate in high-resolution EM structures of integrin bound to an ECM ligands. Therefore, at least in biochemical experiments, integrin dimers must apparently not be 'unbent' in order to prime them and allow their binding to the ECM. In cells, the priming is accomplished by a protein talin, which binds to the β tail of the integrin dimer and changes its conformation. The α and β integrin chains are both class-I transmembrane proteins: they pass the plasma membrane as single transmembrane alpha-helices. Unfortunately, the helices are too long, and recent studies suggest that, for integrin gpIIbIIIa, they are tilted with respect both to one another and to the plane of the membrane. Talin binding alters the angle of tilt of the β3 chain transmembrane helix in model systems and this may reflect a stage in the process of inside-out signalling which primes integrins. Moreover, talin proteins are able to dimerize and thus are thought to intervene in the clustering of integrin dimers which leads to the formation of a focal adhesion. Recently, the Kindlin-1 and Kindlin-2 proteins have also been found to interact with integrin and activate it.
Integrins have two main functions:
- Attachment of the cell to the ECM
- Signal transduction from the ECM to the cell
However, they are also involved in a wide range of other biological activities, including immune patrolling, cell migration, and binding to cells by certain viruses, such as adenovirus, echovirus, hantavirus, and foot and mouth disease viruses.
A prominent function of the integrins is seen in the molecule GPIIbIIIa, an integrin on the surface of blood platelets (thrombocytes) responsible for attachment to fibrin within a developing blood clot. This molecule dramatically increases its binding affinity for fibrin/fibrinogen through association of platelets with exposed collagens in the wound site. Upon association of platelets with collagen, GPIIbIIIa changes shape, allowing it to bind to fibrin and other blood components to form the clot matrix and stop blood loss.
 Attachment of cell to the ECM
Integrins couple the ECM outside a cell to the cytoskeleton (in particular the microfilaments) inside the cell. Which ligand in the ECM the integrin can bind to is defined by which α and β subunits the integrin is made of. Among the ligands of integrins are fibronectin, vitronectin, collagen, and laminin. The connection between the cell and the ECM may help the cell to endure pulling forces without being ripped out of the ECM. The ability of a cell to create this kind of bond is also of vital importance in ontogeny.
Cell attachment to the ECM is a basic requirement to build a multicellular organism. Integrins are not simply hooks, but give the cell critical signals about the nature of its surroundings. Together with signals arising from receptors for soluble growth factors like VEGF, EGF, and many others, they enforce a cellular decision on what biological action to take, be it attachment, movement, death, or differentiation. Thus integrins lie at the heart of many cellular biological processes. The attachment of the cell takes place through formation of cell adhesion complexes, which consist of integrins and many cytoplasmic proteins such as talin, vinculin, paxillin, and alpha-actinin. These act by regulating kinases such as FAK (focal adhesion kinase) and Src kinase family members to phosphorylate substrates such as p130CAS thereby recruiting signaling adaptors such as CRK. These adhesion complexes attach to the actin cytoskeleton. The integrins thus serve to link two networks across the plasma membrane: the extracellular ECM and the intracellular actin filamentous system. Integrin alpha6beta4 is an exception: it links to the keratin intermediate filament system in epithelial cells.
Focal adhesions are large molecular complexes, which are generated following interaction of integrins with ECM, then their clustering. The clusters likely provide sufficient intracellular binding sites to permit the formation of stable signaling complexes on the cytoplasmic side of the cell membrane. So the focal adhesions contain integrin ligand, integrin molecule, and associate plaque proteins. Binding is propelled by changes in free energy. As previously stated, these complexes connect the extracellular matrix to actin bundles. Cryo-electron tomography reveals that the adhesion contains particles on the cell membrane with diameter of 25 +/- 5 nm and spaced at approximately 45 nm. Treatment with Rho-kinase inhibitor Y-27632 reduces the size of the particle, and it is extremely mechanosensitive.
One important function of integrins on cells in tissue culture is their role in cell migration. Cells adhere to a substrate through their integrins. During movement, the cell makes new attachments to the substrate at its front and concurrently releases those at its rear. When released from the substrate, integrin molecules are taken back into the cell by endocytosis; they are transported through the cell to its front by the endocytic cycle where they are added back to the surface. In this way they are cycled for reuse, enabling the cell to make fresh attachments at its leading front. It is not yet clear whether cell migration in tissue culture is an artefact of integrin processing, or whether such integrin dependent cell migration also occurs in living organisms.
 Signal transduction
Integrins play an important role in cell signaling. Connection with ECM molecules can cause a signal to be relayed into the cell through protein kinases that are indirectly and temporarily connected with the intracellular end of the integrin molecule, likely following shape changes directly stimulated by ECM binding.
The signals the cell receives through the integrin can have relation to:
- cell growth,
- cell division,
- cell survival,
- cellular differentiation, and
- apoptosis (programmed cell death).
 Vertebrate integrins
The following are some of the integrins found in vertebrates:
|α4β1||VLA-4||Hematopoietic cells||Fibronectin, VCAM-1|
|α5β1||VLA-5; fibronectin receptor||widespread||fibronectin and proteinases|
|α6β1||VLA-6; laminin receptor||widespread||laminins|
|αMβ2||Mac-1, CR3||Neutrophils and monocytes||Serum proteins, ICAM-1|
|αIIbβ3||Fibrinogen receptor; gpIIbIIIa ||Platelets||fibrinogen, fibronectin|
|αVβ1||ocular melanoma; neurologial tumors||vitronectin; fibrinogen|
|αVβ3||vitronectin receptor||activated endothelial cells, melanoma, glioblastoma||vitronectin, fibronectin, fibrinogen, osteopontin, Cyr61|
|αVβ5||widespread, esp. fibroblasts, epithelial cells||vitronectin and adenovirus|
|αVβ6||proliferating epithelia, esp. lung and mammary gland||fibronectin; TGFβ1+3|
|αVβ8||neural tissue; peripheral nerve||fibronectin; TGFβ1+3|
Beta-1 integrins interact with many alpha integrin chains. Gene knockouts of integrins in mice are not always lethal, which suggests that during embryonal development, one integrin may substitute its function for another in order to allow survival. Some integrins are on the cell surface in an inactive state, and can be rapidly primed, or put into a state capable of binding their ligands, by cytokines. Integrins can assume several different well-defined shapes or "conformational states". Once primed, the conformational state changes to stimulate ligand binding, which then activates the receptors — also by inducing a shape change — to trigger outside-in signal transduction.
- Xiong JP, Stehle T, Diefenbach B, et al. (October 2001). "Crystal structure of the extracellular segment of integrin alpha Vbeta3". Science 294 (5541): 339–45. doi:10.1126/science.1064535. PMC 2885948. PMID 11546839.
- Sauer FG, Fütterer K, Pinkner JS, Dodson KW, Hultgren SJ, Waksman G (August 1999). "Structural basis of chaperone function and pilus biogenesis". Science 285 (5430): 1058–61. doi:10.1126/science.285.5430.1058. PMID 10446050.
- Humphries M.J. (2000). "Integrin structure". Biochem. Soc. Trans. 28 (4): 311–339. doi:10.1042/0300-5127:0280311. PMID 10961914.
- Nermut MV, Green NM, Eason P, Yamada SS, Yamada KM (December 1988). "Electron microscopy and structural model of human fibronectin receptor". EMBO J. 7 (13): 4093–9. PMC 455118. PMID 2977331.
- Hynes R (2002). "Integrins: bidirectional, allosteric signaling machines". Cell 110 (6): 673–87. doi:10.1016/S0092-8674(02)00971-6. PMID 12297042.
- Xiong JP; Stehle, T; Diefenbach, B; Zhang, R; Dunker, R; Scott, DL; Joachimiak, A; Goodman, SL et al. (2001). "Crystal structure of the extracellular segment of integrin αvβ3". Science 294 (5541): 339–345. doi:10.1126/science.1064535. PMC 2885948. PMID 11546839.
- Smith J (2003). "Cilengitide Merck". Curr Opin Investig Drugs 4 (6): 741–5. PMID 12901235.
- Calderwood DA (June 2004). "Talin controls integrin activation". Biochem. Soc. Trans. 32 (Pt3): 434–7. doi:10.1042/BST0320434. PMID 15157154.
- Calderwood DA, Zent R, Grant R, Rees DJ, Hynes RO, Ginsberg MH (October 1999). "The Talin head domain binds to integrin beta subunit cytoplasmic tails and regulates integrin activation". J. Biol. Chem. 274 (40): 28071–4. doi:10.1074/jbc.274.40.28071. PMID 10497155.
- Shattil SJ, Kim C, Ginsberg MH (2010). "The final steps of integrin activation: the end game". Nat Rev Mol.Cell Biol. 11: 288–300. doi:10.1038/nrm2871. PMID 20308986.
- Goldmann WH, Bremer A, Häner M, Aebi U, Isenberg G (1994). "Native talin is a dumbbell-shaped homodimer when it interacts with actin". J. Struct. Biol. 112 (1): 3–10. doi:10.1006/jsbi.1994.1002. PMID 8031639.
- Harburger DS, Bouaouina M, Calderwood DA (April 2009). "Kindlin-1 and −2 directly bind the C-terminal region of beta integrin cytoplasmic tails and exert integrin-specific activation effects". J. Biol. Chem. 284 (17): 11485–97. doi:10.1074/jbc.M809233200. PMC 2670154. PMID 19240021.
- Olberding JE, Thouless MD, Arruda EM, Garikipati K (2010). "The non-equilibrium thermodynamics and kinetics of focal adhesion dynamics". In Buehler, Markus J. PLoS ONE 5 (8): e12043. doi:10.1371/journal.pone.0012043. PMC 2923603. PMID 20805876.
- Patla I, Volberg T, Elad N, Hirschfeld-Warneken V, Grashoff C, Fässler R, Spatz JP, Geiger B, Medalia O (September 2010). "Dissecting the molecular architecture of integrin adhesion sites by cryo-electron tomography". Nat. Cell Biol. 12 (9): 909–15. doi:10.1038/ncb2095. PMID 20694000.
- Gullingsrud J, Sotomayor M. "Mechanosensitive channels". Theoretical and Computational Biophysics Group, Beckman Institute for Advanced Science and Technology: University of Illinois at Urbana-Champaign.
- Benjamin Lewin (2007). Cells. Jones & Bartlett Learning. pp. 671–. ISBN 978-0-7637-3905-8. Retrieved 26 November 2010.
- Krieger M, Scott MP, Matsudaira PT, Lodish HF, Darnell JE, Zipursky L, Kaiser C, Berk A (2004). Molecular cell biology (fifth ed.). New York: W.H. Freeman and CO. ISBN 0-7167-4366-3.
- http://www.vetpathology.org/cgi/reprint/34/1/61.pdf Vet Path01 34:61-73 (1997)
- Hermann P, Armant M, Brown E, Rubio M, Ishihara H, Ulrich D, Caspary RG, Lindberg FP, Armitage R, Maliszewski C, Delespesse G, Sarfati M (February 1999). "The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23". J. Cell Biol. 144 (4): 767–75. doi:10.1083/jcb.144.4.767. PMC 2132927. PMID 10037797.
Media related to Integrins at Wikimedia Commons
- MBInfo - Integrins
- The Integrin Protein
- Talin substrate for calpain – PMAP The Proteolysis Map animation.
- Integrins at the US National Library of Medicine Medical Subject Headings (MeSH)
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.
Integrin beta tail domain Provide feedback
This is the beta tail domain of the Integrin protein. Integrins are receptors which are involved in cell-cell and cell-extracellular matrix interactions.
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR012896
Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways [PUBMED:12297042, PUBMED:12361595]. The integrin receptors are composed of alpha and beta subunit heterodimers. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a vWA domain inserted within the integrin domain at the N terminus.
Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits [PUBMED:12234368]. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans [PUBMED:14689578]. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule [PUBMED:2467745]. Each association of alpha and beta subunits has its own binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activate or inhibit another.
The structure of unliganded alphaV beta3 showed the molecule to be folded, with the head bent over towards the C termini of the legs which would normally be inserted into the membrane [PUBMED:12714499]. The head comprises a beta propeller domain at the end terminus of the alphaV subunit and an I/A domain inserted into a loop on the top of the hybrid domain in the beta subunit. The I/A domain consists of a Rossman fold with a core of beta parallel sheets surrounded by amphipathic alpha helices.
This entry represents the tail domain of the integrin beta subunit. It forms a four-stranded beta-sheet that contains parallel and anttparallel strands and faces an alpha helix found at the N terminus of this domain [PUBMED:11546839]. Interactions between the alpha-helix and the beta-sheet are mostly hydrophobic and involve a disulphide bond. The rear of the beta sheet is covered with a long A-B loop.
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:
- 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
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, 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 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.
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
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.
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
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.
|Seed source:||Pfam-B_1876 (release 14.0)|
|Number in seed:||58|
|Number in full:||524|
|Average length of the domain:||83.70 aa|
|Average identity of full alignment:||32 %|
|Average coverage of the sequence by the domain:||9.93 %|
|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:||7|
|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
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:
- 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
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.
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 Integrin_B_tail domain has been found. There are 21 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...