Summary: Hsp70 protein
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Hsp70 Edit Wikipedia article
|SCOP2||3hsc / SCOPe / SUPFAM|
The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. Intracellularly localized Hsp70s are an important part of the cell's machinery for protein folding, performing chaperoning functions, and helping to protect cells from the adverse effects of physiological stresses. Additionally, membrane-bound Hsp70s have been identified as a potential target for cancer therapies and their extracellularly localized counterparts have been identified as having both membrane-bound and membrane-free structures.
Members of the Hsp70 family are very strongly upregulated by heat stress and toxic chemicals, particularly heavy metals such as arsenic, cadmium, copper, mercury, etc. Heat shock was originally discovered by Ferruccio Ritossa in the 1960s when a lab worker accidentally boosted the incubation temperature of Drosophila (fruit flies). When examining the chromosomes, Ritossa found a "puffing pattern" that indicated the elevated gene transcription of an unknown protein. This was later described as the "Heat Shock Response" and the proteins were termed the "Heat Shock Proteins" (Hsps).
The Hsp70 proteins have three major functional domains:
- N-terminal ATPase domain â€“ binds ATP (Adenosine triphosphate) and hydrolyzes it to ADP (Adenosine diphosphate). The NBD (nucleotide binding domain) consists of two lobes with a deep cleft between them, at the bottom of which nucleotide (ATP and ADP) binds. The exchange of ATP and ADP leads to conformational changes in the other two domains.
- Substrate binding domain â€“ is composed of a 15 kDa Î² sheet subdomain and a 10 kDa helical subdomain. The Î² sheet subdomain consists of stranded Î² sheets with upward protruding loops, as a typical Î² barrel, which enclose the peptide backbone of the substrate. SBD contains a groove with an affinity for neutral, hydrophobic amino acid residues. The groove is long enough to interact with peptides up to seven residues in length.
- C-terminal domain â€“ rich in alpha helical structure acts as a 'lid' for the substrate binding domain. The helical subdomain consists of five helices, with two helices packed against two sides of the Î² sheet subdomain, stabilizing the inner structure. In addition, one of the helix forms a salt bridge and several hydrogen bonds to the outer Loops, thereby closing the substrate-binding pocket like a lid. Three helices in this domain form another hydrophobic core which may be stabilization of the "lid". When an Hsp70 protein is ATP bound, the lid is open and peptides bind and release relatively rapidly. When Hsp70 proteins are ADP bound, the lid is closed, and peptides are tightly bound to the substrate binding domain.
Protein phosphorylation, a post-translational modification, helps to regulate protein function and involves the phosphorylation of amino acids with hydroxyl groups in their side chains (among eukaryotes). Serine, threonine, and tyrosine amino acids are common targets of phosphorylation. Phosphorylation of Hsp70 has become a point of greater exploration in scientific literature relatively recently. A 2020 publication suggests that phosphorylation of a serine residue between the NBD and substrate binding domain in yeast Hsp70s leads to a dramatic reduction of the normal Hsp70 heat shock response. This deactivation via phosphorylation of a protein is a common motif in protein regulation, and demonstrates how relatively small changes to protein structure can have biologically significant effects on protein function.
Function and Regulation
The Hsp70 system interacts with extended peptide segments of proteins as well as partially folded proteins to cause aggregation of proteins in key pathways to downregulate activity. When not interacting with a substrate peptide, Hsp70 is usually in an ATP bound state. Hsp70 by itself is characterized by a very weak ATPase activity, such that spontaneous hydrolysis will not occur for many minutes. As newly synthesized proteins emerge from the ribosomes, the substrate binding domain of Hsp70 recognizes sequences of hydrophobic amino acid residues, and interacts with them. This spontaneous interaction is reversible, and in the ATP bound state Hsp70 may relatively freely bind and release peptides. However, the presence of a peptide in the binding domain stimulates the ATPase activity of Hsp70, increasing its normally slow rate of ATP hydrolysis. When ATP is hydrolyzed to ADP the binding pocket of Hsp70 closes, tightly binding the now-trapped peptide chain. Further speeding ATP hydrolysis are the so-called J-domain cochaperones: primarily Hsp40 in eukaryotes, and DnaJ in prokaryotes. These cochaperones dramatically increase the ATPase activity of Hsp70 in the presence of interacting peptides.
By binding tightly to partially synthesized peptide sequences (incomplete proteins), Hsp70 prevents them from aggregating and being rendered nonfunctional. Once the entire protein is synthesized, a nucleotide exchange factor (prokaryotic GrpE, eukaryotic BAG1 and HspBP1 are among those which have been identified) stimulates the release of ADP and binding of fresh ATP, opening the binding pocket. The protein is then free to fold on its own, or to be transferred to other chaperones for further processing. HOP (the Hsp70/Hsp90 Organizing Protein) can bind to both Hsp70 and Hsp90 at the same time, and mediates the transfer of peptides from Hsp70 to Hsp90.
Hsp70 also aids in transmembrane transport of proteins, by stabilizing them in a partially folded state. It is also known to be phosphorylated which regulates several of its functions.
Hsp70 proteins can act to protect cells from thermal or oxidative stress. These stresses normally act to damage proteins, causing partial unfolding and possible aggregation. By temporarily binding to hydrophobic residues exposed by stress, Hsp70 prevents these partially denatured proteins from aggregating, and inhibits them from refolding. Low ATP is characteristic of heat shock and sustained binding is seen as aggregation suppression, while recovery from heat shock involves substrate binding and nucleotide cycling. In a thermophile anaerobe (Thermotoga maritima) the Hsp70 demonstrates redox sensitive binding to model peptides, suggesting a second mode of binding regulation based on oxidative stress.
Hsp70 seems to be able to participate in disposal of damaged or defective proteins. Interaction with CHIP (Carboxyl-terminus of Hsp70 Interacting Protein)â€“an E3 ubiquitin ligaseâ€“allows Hsp70 to pass proteins to the cell's ubiquitination and proteolysis pathways.
Finally, in addition to improving overall protein integrity, Hsp70 directly inhibits apoptosis. One hallmark of apoptosis is the release of cytochrome c, which then recruits Apaf-1 and dATP/ATP into an apoptosome complex. This complex then cleaves procaspase-9, activating caspase-9 and eventually inducing apoptosis via caspase 3 activation. Hsp70 inhibits this process by blocking the recruitment of procaspase-9 to the Apaf-1/dATP/cytochrome c apoptosome complex. It does not bind directly to the procaspase-9 binding site, but likely induces a conformational change that renders procaspase-9 binding less favorable. Hsp70 is shown to interact with Endoplasmic reticulum stress sensor protein IRE1alpha thereby protecting the cells from ER stress - induced apoptosis. This interaction prolonged the splicing of XBP-1 mRNA thereby inducing transcriptional upregulation of targets of spliced XBP-1 like EDEM1, ERdj4 and P58IPK rescuing the cells from apoptosis. Other studies suggest that Hsp70 may play an anti-apoptotic role at other steps, but is not involved in Fas-ligand-mediated apoptosis (although Hsp 27 is). Therefore, Hsp70 not only saves important components of the cell (the proteins) but also directly saves the cell as a whole. Considering that stress-response proteins (like Hsp70) evolved before apoptotic machinery, Hsp70's direct role in inhibiting apoptosis provides an interesting evolutionary picture of how more recent (apoptotic) machinery accommodated previous machinery (Hsps), thus aligning the improved integrity of a cell's proteins with the improved chances of that particular cell's survival.
Hsp70 is overexpressed in malignant melanoma and underexpressed in renal cell cancer. In breast cancer cell line (MCF7) has been found that not only Hsp90 interacted with estrogen receptor alpha (ERÎ±) but also Hsp70-1 and Hsc70 interacted with ERÎ± too.
Given the role of heat shock proteins as an ancient defense system for stabilizing cells and eliminating old and damaged cells, this system has been co-opted by cancer cells to promote their growth. Increased Hsp70 in particular has been shown to inhibit apoptosis of cancer cells, and increased Hsp70 has been shown to be associated with or directly induce endometrial, lung, colon, prostate, and breast cancer, as well as leukemia. Hsp70 in cancer cells may be responsible for tumorigenesis and tumor progression by providing resistance to chemotherapy. Inhibition of Hsp70 has been shown to reduce the size of tumors and can cause their complete regression. Hsp70/Hsp90 is a particularly attractive target for therapeutics, because it is regulated by the inhibition of its ATPase activity, while other HSPs are regulated by nucleotides. Several inhibitors have been designed for Hsp70 that are currently in clinical trials, though as of now HSP90 inhibitors have been more successful. In addition, Hsp70 has been shown to be a regulator of the immune system, activating the immune system as an antigen. Thus, tumor-derived Hsp70 has been suggested as a potential vaccine  or avenue to target for immunotherapy. Given the increased expression of Hsp70 in cancer, it has been suggested as a biomarker for cancer prognostics, with high levels portending poor prognosis.
Expression in Skin Tissue
Both Hsp70 and HSP47 were shown to be expressed in dermis and epidermis following laser irradiation, and the spatial and temporal changes in HSP expression patterns define the laser-induced thermal damage zone and the process of healing in tissues. Hsp70 may define biochemically the thermal damage zone in which cells are targeted for destruction, and HSP47 may illustrate the process of recovery from thermally induced damage.
Inhibition of Hsp90 leads to Hsp70 and Hsp40 upregulation, which can channel misfolded protein for proteasome degradation, which can potentially inhibit the progression of neurodegenerative diseases. For example, Hsp70 overexpression in human neuroglioma cells transfected with mutant alpha-synuclein led to 50% less oligomeric alpha-synuclein species, pointing towards the possibility that increasing its expression could diminish the spread of Parkinsonâ€™s disease. Similarly, Hsp70 overexpression suppressed poly-Q dependent aggregation and neurodegeneration in cell cultures, yeast, fly, and mouse  models, and deletion of hsp70 increased the size of polyQ inclusion bodies, suggesting that increasing its expression could help to prevent Huntingtonâ€™s disease. Similarly, reductions in Hsp70 have been shown in transgenic mouse models of ALS and patients with sporadic ALS. Lastly, increased expression or activity of Hsp70 has been proposed as a method to prevent the progression of Alzheimerâ€™s disease, because knock down of Hsp70 promoted A-beta toxicity, and Hsp70 was shown to promote tau stability, while Hsp70 levels are decreased in tauopathies like Alzheimerâ€™s disease. Given the complex interplay between the different chaperone proteins, therapeutic development in this field is aimed at investigating how the chaperone network as a whole can be manipulated and the effect of this manipulation on the progression of neurodegenerative disease, but the balance of Hsp70 and Hsp90 levels appears to be central in this pathophysiology.
Prokaryotes express three Hsp70 proteins: DnaK, HscA (Hsc66), and HscC (Hsc62).
Eukaryotic organisms express several slightly different Hsp70 proteins. All share the common domain structure, but each has a unique pattern of expression or subcellular localization. These are, among others:
- Hsc70 (Hsp73/HSPA8) is a constitutively expressed chaperone protein. It typically makes up one to three percent of total cellular protein.
- Hsp70 (encoded by three very closely related paralogs: HSPA1A, HSPA1B, and HSPA1L) is a stress-induced protein. High levels can be produced by cells in response to hyperthermia, oxidative stress, and changes in pH.
- Binding immunoglobulin protein (BiP or Grp78) is a protein localized to the endoplasmic reticulum. It is involved in protein folding there, and can be upregulated in response to stress or starvation.
- mtHsp70 or Grp75 is the mitochondrial Hsp70.
The following is a list of human Hsp70 genes and their corresponding proteins:
Hsps 90 and 110
Hsp90s are essential for protein remodeling, similar to Hsp70 proteins, and play an especially vital role in eukaryotes, where it has been suggested that Hsp90 interacts with the DnaK system (composed of DnaK, GrpE, and either DnaJ or CbpA) to facilitate the process of protein remodeling. In E. coli, Hsp90s works collaboratively with Hsp70s to facilitate protein remodeling and activation. Hsp90Ec and DnaK are chaperones of Hsp90 and Hsp70, respectively. DnaK initially binds and stabilizes the misfolded protein before working collaboratively with Hsp90Ec to refold this substrate and cause its activation. Given conditions of excess DnaK, this chaperone has been found to inhibit remodeling of proteins. However, the presence of Hsp90Ec can mitigate this effect and enable protein remodeling despite conditions of excess DnaK.
The Hsp70 superfamily also includes a family of Hsp110/Grp170 (Sse) proteins, which are larger proteins related to Hsp70. The Hsp110 family of proteins have divergent functions: yeast Sse1p has little ATPase activity but is a chaperone on its own as well as a nucleotide exchange factor for Hsp70, while the closely related Sse2p has little unfoldase activity.
The following is a list of currently named human HSP110 genes. HSPH2-4 are proposed names and the current name is linked:
|HSPH2||HSPA4; APG-2; HSP110||Cyto|
|HSPH4||HYOU1/Grp170; ORP150; HSP12A||ER|
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- Truman AW, Kristjansdottir K, Wolfgeher D, Hasin N, Polier S, Zhang H, etÂ al. (December 2012). "CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression". Cell. 151 (6): 1308â€“18. doi:10.1016/j.cell.2012.10.051. PMCÂ 3778871. PMIDÂ 23217712.
- Muller P, Ruckova E, Halada P, Coates PJ, Hrstka R, Lane DP, Vojtesek B (June 2013). "C-terminal phosphorylation of Hsp70 and Hsp90 regulates alternate binding to co-chaperones CHIP and HOP to determine cellular protein folding/degradation balances". Oncogene. 32 (25): 3101â€“10. doi:10.1038/onc.2012.314. PMIDÂ 22824801. S2CIDÂ 12604151.
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- Wacker JL, Zareie MH, Fong H, Sarikaya M, Muchowski PJ (December 2004). "Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer". Nature Structural & Molecular Biology. 11 (12): 1215â€“22. doi:10.1038/nsmb860. PMIDÂ 15543156. S2CIDÂ 43035.
- Wacker JL, Huang SY, Steele AD, Aron R, Lotz GP, Nguyen Q, etÂ al. (July 2009). "Loss of Hsp70 exacerbates pathogenesis but not levels of fibrillar aggregates in a mouse model of Huntington's disease". The Journal of Neuroscience. 29 (28): 9104â€“14. doi:10.1523/JNEUROSCI.2250-09.2009. PMCÂ 2739279. PMIDÂ 19605647.
- Chen HJ, Mitchell JC, Novoselov S, Miller J, Nishimura AL, Scotter EL, etÂ al. (May 2016). "The heat shock response plays an important role in TDP-43 clearance: evidence for dysfunction in amyotrophic lateral sclerosis". Brain. 139 (Pt 5): 1417â€“32. doi:10.1093/brain/aww028. PMCÂ 4845254. PMIDÂ 26936937.
- Brehme M, Voisine C, Rolland T, Wachi S, Soper JH, Zhu Y, etÂ al. (November 2014). "A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease". Cell Reports. 9 (3): 1135â€“50. doi:10.1016/j.celrep.2014.09.042. PMCÂ 4255334. PMIDÂ 25437566.
- Dou F, Netzer WJ, Tanemura K, Li F, Hartl FU, Takashima A, etÂ al. (January 2003). "Chaperones increase association of tau protein with microtubules". Proceedings of the National Academy of Sciences of the United States of America. 100 (2): 721â€“6. Bibcode:2003PNAS..100..721D. doi:10.1073/pnas.242720499. PMCÂ 141063. PMIDÂ 12522269.
- Yoshimune K, Yoshimura T, Nakayama T, Nishino T, Esaki N (May 2002). "Hsc62, Hsc56, and GrpE, the third Hsp70 chaperone system of Escherichia coli". Biochemical and Biophysical Research Communications. 293 (5): 1389â€“95. doi:10.1016/S0006-291X(02)00403-5. PMIDÂ 12054669.
- Genest O, Hoskins JR, Camberg JL, Doyle SM, Wickner S (May 2011). "Heat shock protein 90 from Escherichia coli collaborates with the DnaK chaperone system in client protein remodeling". Proceedings of the National Academy of Sciences of the United States of America. 108 (20): 8206â€“11. Bibcode:2011PNAS..108.8206G. doi:10.1073/pnas.1104703108. PMCÂ 3100916. PMIDÂ 21525416.
- Genest O, Wickner S, Doyle SM (February 2019). "Hsp90 and Hsp70 chaperones: Collaborators in protein remodeling". The Journal of Biological Chemistry. 294 (6): 2109â€“2120. doi:10.1074/jbc.REV118.002806. PMCÂ 6369297. PMIDÂ 30401745.
- Kampinga HH, Hageman J, Vos MJ, Kubota H, Tanguay RM, Bruford EA, etÂ al. (January 2009). "Guidelines for the nomenclature of the human heat shock proteins". Cell Stress & Chaperones. 14 (1): 105â€“11. doi:10.1007/s12192-008-0068-7. PMCÂ 2673902. PMIDÂ 18663603.
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.
Hsp70 protein Provide feedback
Hsp70 chaperones help to fold many proteins. Hsp70 assisted folding involves repeated cycles of substrate binding and release. Hsp70 activity is ATP dependent. Hsp70 proteins are made up of two regions: the amino terminus is the ATPase domain and the carboxyl terminus is the substrate binding region.
Internal database links
|SCOOP:||Actin BcrAD_BadFG DDR EutA FGGY_C FtsA Hydantoinase_A MreB_Mbl Peripla_BP_6 PilM_2 Ppx-GppA Radial_spoke_3 StbA|
|Similarity to PfamA using HHSearch:||MreB_Mbl FtsA|
External database links
|Transporter classification:||1.A.33 3.A.9|
This tab holds annotation information from the InterPro database.
InterPro entry IPR013126
Heat shock proteins, Hsp70 chaperones help to fold many proteins. Hsp70 assisted folding involves repeated cycles of substrate binding and release. Hsp70 activity is ATP dependent. Hsp70 proteins are made up of two regions: the amino terminus is the ATPase domain and the carboxyl terminus is the substrate binding region [ PUBMED:9476895 ].
Hsp70 proteins have an average molecular weight of 70kDa [ PUBMED:2686623 , PUBMED:2944601 , PUBMED:3282176 ]. In most species, there are many proteins that belong to the Hsp70 family. Some of these are only expressed under stress conditions (strictly inducible), while some are present in cells under normal growth conditions and are not heat-inducible (constitutive or cognate) [ PUBMED:2143562 , PUBMED:2841196 ]. Hsp70 proteins can be found in different cellular compartments (nuclear, cytosolic, mitochondrial, endoplasmic reticulum, for example).
This entry represents the Hsp70 family, and includes chaperone protein DnaK and luminal-binding proteins. It also includes heat shock protein 110 (Hsp110) from Caenorhabditis elegans which helps prevent the aggregation of denatured proteins in neurons [ PUBMED:19165329 ]. Also included is endoplasmic reticulum (ER) chaperone BiP (HSPA5) which is important for protein folding and quality control in the ER [ PUBMED:26655470 ].
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...
The actin-like ATPase domain forms an alpha/beta canonical fold. The domain can be subdivided into 1A, 1B, 2A and 2B subdomains. Subdomains 1A and 1B share the same RNAseH-like fold (a five-stranded beta-sheet decorated by a number of alpha-helices). Domains 1A and 2A are conserved in all members of this superfamily, whereas domain 1B and 2B have a variable structure and are even missing from some homologues . Within the actin-like ATPase domain the ATP-binding site is highly conserved. The phosphate part of the ATP is bound in a cleft between subdomains 1A and 2A, whereas the adenosine moiety is bound to residues from domains 2A and 2B.
The clan contains the following 34 members:Acetate_kinase Actin Actin_micro ALP_N AnmK BcrAD_BadFG Carbam_trans_N DDR DUF1464 DUF2229 EutA FGGY_C FGGY_N FtsA Fumble GDA1_CD39 Glucokinase Hexokinase_1 Hexokinase_2 HGD-D HSP70 Hydant_A_N Hydantoinase_A HypF_C MreB_Mbl MutL Pan_kinase PilM_2 Ppx-GppA RACo_C_ter ROK StbA T2SSL TsaD
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
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
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:||Bateman A , Sonnhammer ELL|
|Number in seed:||27|
|Number in full:||54379|
|Average length of the domain:||407.80 aa|
|Average identity of full alignment:||29 %|
|Average coverage of the sequence by the domain:||80.76 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||23|
|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.
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 HSP70 domain has been found. There are 446 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
Loading structure mapping...
AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.