Summary: TCP-1/cpn60 chaperonin 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 "HSP60". 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.
HSP60 Edit Wikipedia article
|TCP-1/cpn60 chaperonin family|
Structure of the bacterial chaperonin GroEL.
Heat shock proteins are generally responsible for preventing damage to proteins in response to high levels of heat. Heat shock proteins are classified into six major families based on their molecular mass: small HSPs, HSP40, HSP60, HSP70, HSP90, and HSP110
HSP60 is implicated in mitochondrial protein import and macromolecular assembly. It may facilitate the correct folding of imported proteins, and may also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. HSP60 interacts with HRAS and with HBV protein X and HTLV-1 protein p40tax. HSP60 belongs to the chaperonin (HSP60) family. Note: This description may include information from UniProtKB.
Alternate Names: 60 kDa chaperonin, Chaperonin 60, CPN60, Heat shock protein 60, HSP-60, HuCHA60, Mitochondrial matrix protein P1, P60 lymphocyte protein, HSPD1
Heat shock protein 60 (HSP60) is a mitochondrial chaperonin that is typically held responsible for the transportation and refolding of proteins from the cytoplasm into the mitochondrial matrix. In addition to its role as a heat shock protein, HSP60 functions as a chaperonin to assist in folding linear amino acid chains into their respective three-dimensional structure. Through the extensive study of groEL, HSP60’s bacterial homolog, HSP60 has been deemed essential in the synthesis and transportation of essential mitochondrial proteins from the cell's cytoplasm into the mitochondrial matrix. Further studies have linked HSP60 to diabetes, stress response, cancer and certain types of immunological disorders.
Not much is known about the function of HSP60. Mammalian HSP60 was first reported as a mitochondrial P1 protein. It was subsequently cloned and sequenced by Radhey Gupta and coworkers. The amino acid sequence showed a strong homology to GroEL. It was initially believed that HSP60 functioned only in the mitochondria and that there was no equivalent protein located in the cytoplasm. Recent discoveries have discredited this claim and have suggested that there is a recognizable difference between HSP60 in the mitochondria and in the cytoplasm. A similar protein structure exists in the chloroplast of certain plants. This protein presence provides evidence for the evolutionary relationship of the development of the mitochondria and the chloroplast by means of endosymbiosis.
Under normal physiological conditions, HSP60 is a 60 kilodalton oligomer composed of monomers that form a complex arranged as two stacked heptameric rings. This double ring structure forms a large central cavity in which the unfolded protein binds via hydrophobic interactions. This structure is typically in equilibrium with each of its individual components: monomers, heptamers, and tetradeceamers. Recent studies have begun to suggest that in addition to its typical location in the mitochondria, HSP60 can also be found in the cytoplasm under normal physiological conditions.
Each subunit of HSP60 has three domains: the apical domain, the equatorial domain, and the intermediate domain. The equatorial domain contains the binding site for ATP and for the other heptameric ring. The intermediate domain binds the equatorial domain and the apical domain together. The intermediate domain induces a conformational change when ATP is bound allowing for an alternation between the hydrophilic and hydrophobic substrate binding sites. In its inactive state, the protein is in a hydrophobic state. When activated by ATP, the intermediate domain undergoes a conformational change that exposes the hydrophilic region. This insures fidelity in protein binding. Chaperonin 10 aids HSP60 in folding by acting as a dome-like cover on the ATP active form of HSP60. This causes the central cavity to enlarge and aids in protein folding. See the above figure for further detail on the structure.
The mitochondrial HSP60 sequence contains a series of G repeats at the C-terminal. The structure and function of this sequence is not quite known. The N-terminal contains a pre-sequence of hydroxylated amino acids, namely arginine, lysine, serine, and threonine, which serve as directors for the importation of the protein into the mitochondria.
The predicted structure of HSP60 includes several vertical sine waves, alpha helices, beta sheets, and 90 degree turns. There are regions of hydrophobicity where the protein presumably spans the membrane. There are also three N-linked glycosylation sites at positions 104, 230, 436. The sequence and secondary structure for the mitochondrial protein are illustrated in the above image obtained from the Protein Data Bank.
Newer information has begun to suggest that the HSP60 found in the mitochondria differs from that of the cytoplasm. With respect to the amino acid sequence, the cytoplasmic HSP60 has an N-terminal sequence not found in the mitochondrial protein. In gel electrophoresis analysis, significant differences were found in the migration of cytoplasmic and mitochondrial HSP60. The cytoplasmic HSP60 contains a signal sequence of 26 amino acids on the N terminus. This sequence is highly degenerate and is capable of folding into amphiphilic helix. Antibodies against HSP60 targeted both the mitochondrial and cytoplasmic form. Nonetheless, antibodies against the signal sequence targeted only the cytoplasmic form. Under normal physiological condition, both are found in relatively equal concentrations. In times of stress or high need of HSP60 in either the cytoplasm or the mitochondria, the cell is capable for compensating by increasing the presence of HSP60 in one compartment and decreasing its concentration in the opposite compartment.
Heat shock proteins are amongst the most evolutionarily conserved of proteins. The significant function, structural, and sequential homology between HSP60 and its prokaryotic homolog, groEL, demonstrates this level of conservation. Moreover, HSP60’s amino acid sequence bears a similarity to its homolog in plants, bacteria, and humans. Heat shock proteins are primarily responsible for maintaining the integrity of cellular proteins particularly in response to environmental changes. Stresses such as temperature, concentration imbalance, pH change, and toxins can all induce heat shock proteins to maintain the conformation of the cell’s proteins. HSP60 aids in the folding and conformation maintenance of approximately 15-30% of all cellular proteins. In addition to HSP60’s typical role as a heat shock protein, studies have shown that HSP60 plays an important role in the transport and maintenance of mitochondrial proteins as well as the transmission and replication of mitochondrial DNA.
Mitochondrial protein transport
HSP60 possesses two main responsibilities with respect to mitochondrial protein transport. It functions to catalyze the folding of proteins destined for the matrix and maintains protein in an unfolded state for transport across the inner membrane of the mitochondria. Many proteins are targeted for processing in the matrix of the mitochondria but then are quickly exported to other parts of the cell. The hydrophobic portion HSP60 is responsible for maintaining the unfolded conformation of the protein for transmembrane transport. Studies have shown how HSP60 binds to incoming proteins and induces conformational and structural changes. Subsequent changes in ATP concentrations hydrolyze the bonds between the protein and HSP60 which signals the protein to exit the mitochondria. HSP60 is also capable of distinguishing between proteins designated for export and proteins destined to remain in the mitochondrial matrix by looking for an amphiphilic alpha-helix of 15-20 residues. The existence of this sequence signals that the protein is to be exported while the absence signals that the protein is to remain in the mitochondria. The precise mechanism is not yet entirely understood.
In addition to its critical role in protein folding, HSP60 is involved in the replication and transmission of mitochondrial DNA. In extensive studies of HSP60 activity in Saccharomyces cerevisiae, scientists have proposed that HSP60 binds preferentially to the single stranded template DNA strand in a tetradecamer like complex  This tetradecamer complex interacts with other transcriptional elements to serve as a regulatory mechanism for the replication and transmission of mitochondrial DNA. Mutagenic studies have further supported HSP60 regulatory involvement in the replication and transmission of mitochondrial DNA.Mutations in HSP60 increase the levels of mitochondrial DNA and result in subsequent transmission defects.
Cytoplasmic vs mitochondrial HSP60
In addition to the already illustrated structural differences between cytoplasmic and mitochondrial HSP60, there are marked functional differences. Studies have suggested that HSP60 plays a key role in preventing apoptosis in the cytoplasm. The cytoplasmic HSP60 forms a complex with proteins responsible for apoptosis and regulates the activity of these proteins. The cytoplasmic version is also involved in immune response and cancer. These two aspects will be elaborated on later. Extremely recent investigations have begun to suggest a regulatory correlation between HSP60 and the glycolytic enzyme, 6-phosphofructokinase-1. Although not much information is available, cytoplasmic HSP60 concentrations have influenced the expression of 6-phosphofructokinase in glycolysis. Despite these marked differences between the cytoplasmic and mitochondrial form, experimental analysis has shown that the cell is quickly capable of moving cytoplasmic HSP60 into the mitochondria if environmental conditions demand a higher presence of mitochondrial HSP60.
Synthesis and assembly
HSP60 is typically found in the mitochondria and has been found in organelles of endosymbiotic origin. HSP60 monomers form two heptameric rings that bind to the surface of linear proteins and catalyze their folding in an ATP dependent process. HSP60 subunits are encoded by nuclear genes and translated into the cytosol. These subunits then move into the mitochondria where they are processed by other HSP60 molecules. Several studies have shown how HSP60 proteins must be present in the mitochondria for the synthesis and assembly of additional HSP60 components. There is a direct positive correlation between the presence of HSP60 proteins in the mitochondria and the production of additional HSP60 protein complexes.
The kinetics of assembly of HSP60 subunits into the 2-heptameric rings takes two minutes. The subsequent protease-resistant HSP60 is formed in a half-time of 5–10 minutes. This rapid synthesis indicates that there is an ATP-dependent interaction where the formed HSP60 complex stabilizes the intermediate of the HSP60 assembly complex, effectively serving as a catalyst. The necessity of preexisting HSP60 in order to synthesize additional HSP60 molecules supports the endosymbiotic theory of the origin of mitochondria. There must have been a rudimentary prokaryotic homologous protein that was capable of similar self-assembly.
As discussed above, HSP60 has generally been known as a chaperonin which assists in protein folding in mitochondria. However, some new research has indicated that HSP60 possibly plays a role in a “danger signal cascade” immune response. There is also mounting evidence that it plays a role in autoimmune disease.
Infection and disease are extremely stressful on the cell. When a cell is under stress, it naturally increases the production of stress proteins, including heat shock proteins such as HSP60. In order for HSP60 to act as a signal it must be present in the extracellular environment. In recent research “it has emerged that…chaperonin 60 can be found on the surface of various prokaryotic and eukaryotic cells, and can even be released from cells”. According to recent research, many different types of heat shock proteins are used in immune response signaling, but it appears that different proteins act and respond differently to other signaling molecules. HSP60 has been shown to be released from specific cells like peripheral blood mononuclear cells (PBMCs) when there are lipopolysaccharides (LPS) or GroEL present. This suggests that the cell has different receptors and responses to human and bacterial HSP60. In addition, it has been shown that HSP60 has the capability “of activating monocytes, macrophages and dendritic cells…and also of inducing secretion of a wide range of cytokines.”  The fact that HSP60 responds to other signal molecules like LPS or GroEL and has the ability to activate certain types of cells supports the idea that HSP60 is part of a danger signal cascade which is involved in activating an immune response.
There is however, a twist in the immunological role of HSP60. As mentioned above, there are two different types of HSP60 proteins, bacterial as well as mammalian. Since they are very similar in sequence, bacterial HSP60 wouldn’t be expected to cause a large immune response in humans. The immune system is “designed to ignore ‘self’, that is, host constituents; however, paradoxically, this is not the case with chaperonins”. It has been found that many anti-chaperonin antibodies exist and are associated with many autoimmune diseases. According to Ranford, et al. experiments have been performed which have shown that antibodies which are “generated by a human host after exposure to bacterial chaperonin 60 proteins” can cross-react with human chaperonin 60 proteins. Bacterial HSP60 is causing the immune system to create anti-chaperonin antibodies, even though bacterial and human HSP60 have similar protein sequences. These new antibodies are then recognizing and attacking human HSP60 which causes an autoimmune disease. This suggests that HSP60 may play a role in autoimmunity, however more research needs to be done in order to discover more completely its role in this disease.
HSP60, as a mitochondrial protein, has been shown to be involved in stress response as well. The heat shock response is a homeostatic mechanism that protects a cell from damage by upregulating the expression of genes that code for HSP60. The upregulation of HSP60 production allows for the maintenance of other cellular processes occurring in the cell, especially during stressful times. In one experiment, investigators treated various mice with L-DOPA and discovered significant upregulation of HSP60 expression in the mitochondria and HSP70 expression in the cytoplasm. Researchers concluded that the heat shock signal pathway serves as “the basic mechanism of defense against neurotoxicity elicited by free radical oxygen and nitrogen species produced in aging and neurodegenerative disorders”. Several studies have shown that HSP60 and other heat shock proteins are necessary for cellular survival under toxic or stressful circumstances.
Relationship to cancer
Human Hsp60, the product of the HSPD1 gene, is a Group I mitochondrial chaperonin, phylogenetically related to bacterial GroEL. Recently, the presence of Hsp60 outside the mitochondria and outside the cell, e.g. in circulating blood, has been reported , . Although it is assumed that Hsp60 extra-mitochondrial molecule is identical to the mitochondrial one, this has not yet been fully elucidated. Despite the increasing amount of experimental evidences showing Hsp60 outside the cell, it is not yet clear how general this process is and what are the mechanisms responsible for Hsp60 translocation outside the cell. Neither of these questions has been definitively answered, whereas there is some information regarding extracellular Hsp70. This chaperone was also classically regarded as an intracellular protein like Hsp60, but in the last few years considerable evidences showed its pericellular and extracellular residence
HSP60 has been shown to influence apoptosis in tumor cells which seems to be associated with a change in expression levels. There is some inconsistency in that some research shows a positive expression while other research shows a negative expression, and it seems to depend on the type of cancer. There are different hypotheses to explain the effects of positive versus negative expression. Positive expression seems to inhibit “apoptotic and necrotic cell death” while negative expression is thought to play a part “in activation of apoptosis”.
As well as influencing apoptosis, HSP60 changes in expression level have been shown to be “useful new biomarkers for diagnostic and prognostic purposes.”  According to Lebret et al., a loss of HSP60 expression “indicates a poor prognosis and the risk of developing tumor infiltration” specifically with bladder carcinomas, but that does not necessarily hold true for other types of cancers. For example, ovarian tumors research has shown that over expression is correlated with a better prognosis while a decreased expression is correlated with an aggressive tumor. All this research indicates that it may be possible for HSP60 expression to be used in predicting survival for certain types of cancer and therefore may be able to identify patients who could benefit from certain treatments.
- Braig K, Otwinowski Z, Hegde R, et al. (October 1994). "The crystal structure of the bacterial chaperonin GroEL at 2.8 A". Nature. 371 (6498): 578–86. doi:10.1038/371578a0. PMID 7935790.
- Johnson RB, et al. (2003). "Cloning and characterization of the yeast chaperonin HSP60 gene". Genetics. 84: 295–300. doi:10.1016/0378-1119(89)90503-9. PMID 2575559.
- Gupta RS (January 1995). "Evolution of the chaperonin families (Hsp60, Hsp10 and Tcp-1) of proteins and the origin of eukaryotic cells". Mol. Microbiol. 15 (1): 1–11. doi:10.1111/j.1365-2958.1995.tb02216.x. PMID 7752884.
- Itoh H, Komatsuda A, Ohtani H, et al. (December 2002). "Mammalian HSP60 is quickly sorted into the mitochondria under conditions of dehydration". Eur. J. Biochem. 269 (23): 5931–8. doi:10.1046/j.1432-1033.2002.03317.x. PMID 12444982.
- Cheng MY, Hartl FU, Horwich AL (November 1990). "The mitochondrial chaperonin hsp60 is required for its own assembly". Nature. 348 (6300): 455–8. doi:10.1038/348455a0. PMID 1978929.
- Fenton WA, et al. (October 1994). "Residues in chaperonin GroEL required for polypeptide binding and release". Nature. 371: 614–9. doi:10.1038/371614a0. PMID 7935796.
- Habich C, et al. (March 2007). "Heat shock protein 60: regulatory role on innate immune cells". Cell. Mol. Life Sci. 64: 742–51. doi:10.1007/s00018-007-6413-7. PMID 17221165.
- Ranford JC, et al. (September 2000). "Chaperonins are cell-signalling proteins: the unfolding biology of molecular chaperones". Expert Rev Mol Med. 2: 1–17. doi:10.1017/S1462399400002015. PMID 14585136.
- doi:10.1107/S0907444999003698. PMID 10329779.; Walsh MA, et al. (June 1999). "Taking MAD to the extreme: ultrafast protein structure determination". Acta Crystallogr. D. 55: 1168–73.
- Koll H, et al. (March 1992). "Antifolding activity of hsp60 couples protein import into the mitochondrial matrix with export to the intermembrane space". Cell. 68: 1163–75. doi:10.1016/0092-8674(92)90086-R. PMID 1347713.
- Kaufman, BA. Studies on mitochondria DNA nucleoids in Saccharomyces cerevisia: identification of bifunctional proteins. In Genetics and Development, UT Southwestern Medical Center at Dallas, Dallas, TX. 241pp.
- Kaufman, B. A. (2003). "A function for the mitochondrial chaperonin Hsp60 in the structure and transmission of mitochondrial DNA nucleoids in Saccharomyces cerevisiae". The Journal of Cell Biology. 163 (3): 457–461. doi:10.1083/jcb.200306132. ISSN 0021-9525. PMC . PMID 14597775.
- Koll H, et al. (1992). "Antifolding Activity of HSP60 Couples Protein Import into the Mitochondrial Matrix with Export to the Intermembrane Space". Cell. 68 (6): 1163–75. doi:10.1016/0092-8674(92)90086-R. PMID 1347713.
- Itoh H, et al. (December 2002). "Mammalian HSP60 is quickly sorted into the mitochondria under conditions of dehydration". European J. Biochem. 269: 5931–8. doi:10.1046/j.1432-1033.2002.03317.x. PMID 12444982.
- Hansen JJ, Bross P, Westergaard M, et al. (January 2003). "Genomic structure of the human mitochondrial chaperonin genes: HSP60 and HSP10 are localised head to head on chromosome 2 separated by a bidirectional promoter". Hum. Genet. 112 (1): 71–7. doi:10.1007/s00439-002-0837-9. PMID 12483302.
- Vargas-Parada L, Solis C (2001). "Heat Shock and stress response of Taenia solium and T. crassiceps". Parasitology. 122: 583–8. doi:10.1017/s0031182001007764.
- Calabrese V, Mancuso C, Ravagna A, et al. (May 2007). "In vivo induction of heat shock proteins in the substantia nigra following L-DOPA administration is associated with increased activity of mitochondrial complex I and nitrosative stress in rats: regulation by glutathione redox state". J. Neurochem. 101: 709–17. doi:10.1111/j.1471-4159.2006.04367.x. PMID 17241115.
- Rossi MR, Somji S, Garrett SH, Sens MA, Nath J, Sens DA (December 2002). "Expression of hsp 27, hsp 60, hsc 70, and hsp 70 stress response genes in cultured human urothelial cells (UROtsa) exposed to lethal and sublethal concentrations of sodium arsenite". Environ. Health Perspect. 110: 1225–32. doi:10.1289/ehp.021101225. PMC . PMID 12460802.
- Cappello F, Di Stefano A, David S, et al. (November 2006). "Hsp60 and Hsp10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease". Cancer. 107 (10): 2417–24. doi:10.1002/cncr.22265. PMID 17048249.
- Urushibara M, Kageyama Y, Akashi T, et al. (January 2007). "HSP60 may predict good pathological response to neoadjuvant chemoradiotherapy in bladder cancer". Jpn. J. Clin. Oncol. 37 (1): 56–61. doi:10.1093/jjco/hyl121. PMID 17095522.
- Lebret T, Watson RW, Molinié V, et al. (September 2003). "Heat shock proteins HSP27, HSP60, HSP70, and HSP90: expression in bladder carcinoma". Cancer. 98 (5): 970–7. doi:10.1002/cncr.11594. PMID 12942564.
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.
TCP-1/cpn60 chaperonin family Provide feedback
This family includes members from the HSP60 chaperone family and the TCP-1 (T-complex protein) family.
Internal database links
|SCOOP:||REF DUF1308 Pho88|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR002423
The assembly of proteins has been thought to be the sole result of properties inherent in the primary sequence of polypeptides themselves. In some cases, however, structural information from other protein molecules is required for correct folding and subsequent assembly into oligomers [PUBMED:2897629]. These 'helper' molecules are referred to as molecular chaperones, a subfamily of which are the chaperonins [PUBMED:1349837], which include 10 kDa and 60 kDa proteins. These are found in abundance in prokaryotes, chloroplasts and mitochondria. They are required for normal cell growth (as demonstrated by the fact that no temperature sensitive mutants for the chaperonin genes can be found in the temperature range 20 to 43 degrees centigrade [PUBMED:2897629]), and are stress-induced, acting to stabilise or protect disassembled polypeptides under heat-shock conditions [PUBMED:1349837].
The 10 kDa chaperonin (cpn10 - or groES in bacteria) exists as a ring-shaped oligomer of between 6 to 8 identical subunits, whereas the 60 kDa chaperonin (cpn60 - or groEL in bacteria) forms a structure comprising 2 stacked rings, each ring containing 7 identical subunits [PUBMED:2897629]. These ring structures assemble by self-stimulation in the presence of Mg2+-ATP. The cpn10 and cpn60 oligomers also require Mg2+-ATP in order to interact to form a functional complex, although the mechanism of this interaction is as yet unknown [PUBMED:1350777]. This chaperonin complex is essential for the correct folding and assembly of polypeptides into oligomeric structures, of which the chaperonins themselves are not a part [PUBMED:1349837]. The binding of cpn10 to cpn60 inhibits the weak ATPase activity of cpn60.
TCP-1 (t-complex polypeptide 1) is a subunit of the hetero-oligomeric complex CCT (chaperonin containing TCP- 1) present in the eukaryotic cytosol. It is a member of the chaperonin family which includes GroEL, 60 kDa heat shock protein (Hsp60), Rubisco subunit binding protein (RBP) and thermophilic factor 55 (TF55) [PUBMED:7601114].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||ATP binding (GO:0005524)|
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 (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.
|Author:||Sonnhammer ELL, Finn RD|
|Number in seed:||57|
|Number in full:||12754|
|Average length of the domain:||429.30 aa|
|Average identity of full alignment:||26 %|
|Average coverage of the sequence by the domain:||72.42 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||22|
|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 2 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 Cpn60_TCP1 domain has been found. There are 1215 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...