Summary: P53 DNA-binding domain
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|Tumor protein p53|
PDB rendering based on : P53 complexed with DNA
|External IDs||ChEMBL: GeneCards:|
|RNA expression pattern|
p53 (also known as protein 53 or tumor protein 53), is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer. As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation.
The name p53 is in reference to its apparent molecular mass: It runs as a 53-kilodalton (kDa) protein on SDS-PAGE. But, based on calculations from its amino acid residues, p53's mass is actually only 43.7 kDa. This difference is due to the high number of proline residues in the protein, which slows its migration on SDS-PAGE, thus making it appear heavier than it actually is. This effect is observed with p53 from a variety of species, including humans, rodents, frogs, and fish.
p53 is also known as:
- UniProt name: Cellular tumor antigen p53
- Antigen NY-CO-13
- Phosphoprotein p53
- Transformation-related protein 53 (TRP53)
- Tumor suppressor p53
In humans, p53 is encoded by the TP53 gene located on the short arm of chromosome 17 (17p13.1). The gene spans 20 kb, with a non-coding exon 1 and a very long first intron of 10 kb.The coding sequence contains five regions showing a high degree of conservation in vertebrates, predominantly in exons 2, 5, 6, 7 and 8, but the sequences found in invertebrates show only distant resemblance to mammalian TP53. TP53 orthologs have been identified in most mammals for which complete genome data are available.
In humans, a common polymorphism involves the substitution of an arginine for a proline at codon position 72. Many studies have investigated a genetic link between this variation and cancer susceptibility, however, the results have been controversial. For instance, a meta-analysis from 2009 failed to show a link for cervical cancer. A 2011 study found that the TP53 proline mutation did have a profound effect on pancreatic cancer risk among males. A study of Arab women found that proline homozygosity at TP53 codon 72 is associated with a decreased risk for breast cancer. One study suggested that TP53 codon 72 polymorphisms, MDM2 SNP309, and A2164G may collectively be associated with non-oropharyngeal cancer susceptibility and that MDM2 SNP309 in combination with TP53 codon 72 may accelerate the development of non-oropharyngeal cancer in women. A 2011 study found that TP53 codon 72 polymorphism was associated with an increased risk of lung cancer.
Meta-analyses from 2011 found no significant associations between TP53 codon 72 polymorphisms and both colorectal cancer risk and endometrial cancer risk. A 2011 study of a Brazilian birth cohort found an association between the non mutant arginine TP53 and individuals without a family history of cancer. Another 2011 study found that the p53 homozygous (Pro/Pro) genotype was associated with a significantly increased risk for renal cell carcinoma.
(Italics are used to denote the TP53 gene name and distinguish it from the protein it encodes.)
- an acidic N-terminus transcription-activation domain (TAD), also known as activation domain 1 (AD1), which activates transcription factors: residues 1-42. The N-terminus contains two complementary transcriptional activation domains, with a major one at residues 1â42 and a minor one at residues 55â75, specifically involved in the regulation of several pro-apoptotic genes.
- activation domain 2 (AD2) important for apoptotic activity: residues 43-63.
- Proline rich domain important for the apoptotic activity of p53: residues 64-92.
- central DNA-binding core domain (DBD). Contains one zinc atom and several arginine amino acids: residues 102-292. This region is responsible for binding the p53 co-repressor LMO3.
- nuclear localization signaling domain, residues 316-325.
- homo-oligomerisation domain (OD): residues 307-355. Tetramerization is essential for the activity of p53 in vivo.
- C-terminal involved in downregulation of DNA binding of the central domain: residues 356-393.
A tandem of nine-amino-acid transactivation domains (9aaTAD) was identified in the AD1 and AD2 regions of transcription factor p53. KO mutations and position for p53 interaction with TFIID are listed below:
Mutations that deactivate p53 in cancer usually occur in the DBD. Most of these mutations destroy the ability of the protein to bind to its target DNA sequences, and thus prevents transcriptional activation of these genes. As such, mutations in the DBD are recessive loss-of-function mutations. Molecules of p53 with mutations in the OD dimerise with wild-type p53, and prevent them from activating transcription. Therefore OD mutations have a dominant negative effect on the function of p53. An example of a mutation in P53 is where arginine 248 is altered, sometimes causing a disruption in balance and making the protein unable to bind with the DNA.
p53 has many mechanisms of anticancer function, and plays a role in apoptosis, genomic stability, and inhibition of angiogenesis. In its anti-cancer role, p53 works through several mechanisms:
- It can activate DNA repair proteins when DNA has sustained damage.
- It can arrest growth by holding the cell cycle at the G1/S regulation point on DNA damage recognition (if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to continue the cell cycle).
- It can initiate apoptosis, the programmed cell death, if DNA damage proves to be irreparable.
Activated p53 binds DNA and activates expression of several genes including microRNA miR-34a, WAF1/CIP1 encoding for p21 and hundreds of other down-stream genes. p21 (WAF1) binds to the G1-S/CDK (CDK2) and S/CDK complexes (molecules important for the G1/S transition in the cell cycle) inhibiting their activity.
When p21(WAF1) is complexed with CDK2 the cell cannot continue to the next stage of cell division. A mutant p53 will no longer bind DNA in an effective way, and, as a consequence, the p21 protein will not be available to act as the "stop signal" for cell division. Studies of human embryonic stem cells (hESCs) commonly describe the nonfunctional p53-p21 axis of the G1/S checkpoint pathway with subsequent relevance for cell cycle regulation and the DNA damage response (DDR). Importantly, p21 mRNA is clearly present and upregulated after the DDR in hESCs, but p21 protein is not detectable. In this cell type, p53 activates numerous microRNAs (like miR-302a, miR-302b, miR-302c, and miR-302d) that directly inhibit the p21 expression in hESCs.
p53 becomes activated in response to myriad stressors, including but not limited to DNA damage (induced by either UV, IR, or chemical agents such as hydrogen peroxide), oxidative stress, osmotic shock, ribonucleotide depletion, and deregulated oncogene expression. This activation is marked by two major events. First, the half-life of the p53 protein is increased drastically, leading to a quick accumulation of p53 in stressed cells. Second, a conformational change forces p53 to be activated as a transcription regulator in these cells. The critical event leading to the activation of p53 is the phosphorylation of its N-terminal domain. The N-terminal transcriptional activation domain contains a large number of phosphorylation sites and can be considered as the primary target for protein kinases transducing stress signals.
The protein kinases that are known to target this transcriptional activation domain of p53 can be roughly divided into two groups. A first group of protein kinases belongs to the MAPK family (JNK1-3, ERK1-2, p38 MAPK), which is known to respond to several types of stress, such as membrane damage, oxidative stress, osmotic shock, heat shock, etc. A second group of protein kinases (ATR, ATM, CHK1 and CHK2, DNA-PK, CAK, TP53RK) is implicated in the genome integrity checkpoint, a molecular cascade that detects and responds to several forms of DNA damage caused by genotoxic stress. Oncogenes also stimulate p53 activation, mediated by the protein p14ARF.
In unstressed cells, p53 levels are kept low through a continuous degradation of p53. A protein called Mdm2 (also called HDM2 in humans), which is itself a product of p53, binds to p53, preventing its action and transports it from the nucleus to the cytosol. Also Mdm2 acts as ubiquitin ligase and covalently attaches ubiquitin to p53 and thus marks p53 for degradation by the proteasome. However, ubiquitylation of p53 is reversible.
A ubiquitin specific protease, USP7 (or HAUSP), can cleave ubiquitin off p53, thereby protecting it from proteasome-dependent degradation. This is one means by which p53 is stabilized in response to oncogenic insults. USP42 has also been shown to deubiquitinate p53 and may be required for the ability of p53 to respond to stress.
Recent research has shown that HAUSP is mainly localized in the nucleus, though a fraction of it can be found in the cytoplasm and mitochondria. Overexpression of HAUSP results in p53 stabilization. However, depletion of HAUSP does not result to a decrease in p53 levels but rather increases p53 levels due to the fact that HAUSP binds and deubiquitinates Mdm2. It has been shown that HAUSP is a better binding partner to Mdm2 than p53 in unstressed cells.
USP10 however has been shown to be located in the cytoplasm in unstressed cells and deubiquitinates cyptoplasmic p53, reversing Mdm2 ubiquitination. Following DNA damage, USP10 translocates to the nucleus and contributes to p53 stability. Also USP10 does not interact with Mdm2.
Phosphorylation of the N-terminal end of p53 by the above-mentioned protein kinases disrupts Mdm2-binding. Other proteins, such as Pin1, are then recruited to p53 and induce a conformational change in p53, which prevents Mdm2-binding even more. Phosphorylation also allows for binding of transcriptional coactivators, like p300 and PCAF, which then acetylate the carboxy-terminal end of p53, exposing the DNA binding domain of p53, allowing it to activate or repress specific genes. Deacetylase enzymes, such as Sirt1 and Sirt7, can deacetylate p53, leading to an inhibition of apoptosis. Some oncogenes can also stimulate the transcription of proteins that bind to MDM2 and inhibit its activity.
Role in disease
If the TP53 gene is damaged, tumor suppression is severely reduced. People who inherit only one functional copy of the TP53 gene will most likely develop tumors in early adulthood, a disorder known as Li-Fraumeni syndrome. The TP53 gene can also be damaged in cells by mutagens (chemicals, radiation, or viruses), increasing the likelihood that the cell will begin decontrolled division. More than 50 percent of human tumors contain a mutation or deletion of the TP53 gene. Increasing the amount of p53, which may initially seem a good way to treat tumors or prevent them from spreading, is in actuality not a usable method of treatment, since it can cause premature aging. However, restoring endogenous p53 function holds a lot of promise. Research has been done to show that this restoration can lead to regression of certain cancer cells without damaging other cells in the process. The ways in which tumor regression occur depends chiefly on tumor type. With restoration of endogenous p53 function, lymphomas exhibit apoptosis and cell growth is lowered to normal levels. Thus, pharmacological reactivation of p53 presents itself as a viable cancer treatment option. Loss of p53 creates genomic instability that most often results in the aneuploidy phenotype.
Certain pathogens can also affect the p53 protein that the TP53 gene expresses. One such example, human papillomavirus (HPV), encodes a protein, E6, which binds to the p53 protein and inactivates it. This, in synergy with the inactivation of another cell cycle regulator, pRb, by the HPV protein E7, allows for repeated cell division manifested in the clinical disease of warts. Certain HPV types, in particular types 16 and 18, can also lead to progression from a benign wart to low or high-grade cervical dysplasia, which are reversible forms of precancerous lesions. Persistent infection of the cervix over the years can cause irreversible changes leading to carcinoma in situ and eventually invasive cervical cancer. This results from the effects of HPV genes, particularly those encoding E6 and E7, which are the two viral oncoproteins that are preferentially retained and expressed in cervical cancers by integration of the viral DNA into the host genome.
In healthy humans, the p53 protein is continually produced and degraded in the cell. The degradation of the p53 protein is, as mentioned, associated with MDM2 binding. In a negative feedback loop, MDM2 is itself induced by the p53 protein. However, mutant p53 proteins often do not induce MDM2, and are thus able to accumulate at very high concentrations. Worse, mutant p53 protein itself can inhibit normal p53 protein levels. In some cases, single missense mutations in p53 have been shown to disrupt p53 stability and function.
Experimental analysis of p53 mutations
Most p53 mutations are detected by DNA sequencing. However, it is known that single missense mutations can have a large spectrum from rather mild to very severe functional effects.
p53 was identified in 1979 by Lionel Crawford, David P. Lane, Arnold Levine, and Lloyd Old, working at Imperial Cancer Research Fund (UK) Princeton University/UMDNJ (Cancer Institute of New Jersey), and Memorial Sloan-Kettering Cancer Center, respectively. It had been hypothesized to exist before as the target of the SV40 virus, a strain that induced development of tumors. The TP53 gene from the mouse was first cloned by Peter Chumakov of the Russian Academy of Sciences in 1982, and independently in 1983 by Moshe Oren in collaboration with David Givol (Weizmann Institute of Science). The human TP53 gene was cloned in 1984 and the full length clone in 1985.
It was initially presumed to be an oncogene due to the use of mutated cDNA following purification of tumour cell mRNA. Its character as a tumor suppressor gene was finally revealed in 1989 by Bert Vogelstein working at Johns Hopkins School of Medicine.
Warren Maltzman, of the Waksman Institute of Rutgers University first demonstrated that TP53 was responsive to DNA damage in the form of ultraviolet radiation. In a series of publications in 1991-92, Michael Kastan, Johns Hopkins University, reported that TP53 was a critical part of a signal transduction pathway that helped cells respond to DNA damage.
In 1992, Wafik El-Deiry when he was working with Bert Vogelstein at Johns Hopkins University identified the consensus sequence, to which human p53 could bind, by immunoprecipitating human genomic DNA that could be bound by baculovirus-produced human p53 protein. This sequence was published in the first issue of the journal Nature Genetics in 1992 in work that is highly cited. The consensus sequence is 5'-RRRCWWGYYY-N(0-13)-RRRCWWGYYY-3' and is located in the regulatory regions of genes that are activated by the p53 transcription factor. The presence of p53 response elements in or around genes (promoters, upstream sequences, introns) is a powerful predictor of regulation and activation of a particular gene by p53.
That same year, 1993, Wafik El-Deiry when he was working with Bert Vogelstein at Johns Hopkins University discovered p21(WAF1) as a gene regulated directly by p53. This work was reported in the most highly cited paper ever published in the journal Cell, and provided a molecular mechanism by which mammalian cells undergo growth arrest when damaged. The p21(WAF1) protein binds directly to cyclin-CDK complexes that drive forward the cell cycle and inhibits their kinase activity thereby causing cell cycle arrest to allow repair to take place. p21 can also mediate growth arrest associated with differentiation and a more permanent growth arrest associated with cellular senescence. The p21 gene contains several p53 response elements that mediate direct binding of the p53 protein, resulting in transcriptional activation of the gene encoding the p21(WAF1) protein.
p53 has been shown to interact with:
- Cyclin H,
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [Â§ 1]
- The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".
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|Wikimedia Commons has media related to Tumor suppressor protein p53.|
- Lane Group at the Institute of Molecular and Cell Biology (IMCB), Singapore. p53 Knowledgebase [Retrieved 2008-04-06].
- GeneReviews/NCBI/NIH/UW entry on Li-Fraumeni Syndrome
- TUMOR PROTEIN p53 @ OMIM
-  p53 restoration of function
- p53 @ The Atlas of Genetics and Cytogenetics in Oncology and Haematology
- TP53 Gene @ GeneCards
- p53 News provided by insciences organisation
- David S. Goodsell. RCSB Protein Data Bank. p53 Tumor Suppressor; 2002-07-01 [Retrieved 2008-04-06].
- Thierry Soussi. p53 Web Site [Retrieved 2008-04-06].
- The George Pantziarka TP53 Trust A support group from the UK for sufferers of Li-Fraumeni Syndrome or other TP53-related disorders
- IARC TP53 Somatic Mutations database maintained at IARC, Lyon, by Magali Olivier
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.
P53 DNA-binding domain Provide feedback
This family contains one anomalous member, viz: Zea mays (Q6JAD8). This sequence is identical to human P53 and would appear to be a a human contaminant within the Zea mays sampling effort.
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR011615
This domain is found in p53 transcription factors, where it is responsible for DNA-binding. These transcription factors play diverse roles in the regulation of cellular functions: the p53 tumour suppressor upregulates the expression of genes involved in cell cycle arrest and apoptosis [PUBMED:12826037]. The DNA-binding domain acts to clamp, or in the case of TonEBP, encircle the DNA target in order to stabilise the protein-DNA complex [PUBMED:11780147]. Protein interactions may also serve to stabilise the protein-DNA complex, for example in the STAT-1 dimer the SH2 (Src homology 2) domain in each monomer is coupled to the DNA-binding domain to increase stability [PUBMED:9630226]. The DNA-binding domain consists of a beta-sandwich formed of 9 strands in 2 sheets with a Greek-key topology. This structure is found in many transcription factors, often within the DNA-binding domain.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||transcription regulatory region DNA binding (GO:0044212)|
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_782 (release 3.0)|
|Number in seed:||7|
|Number in full:||550|
|Average length of the domain:||158.10 aa|
|Average identity of full alignment:||54 %|
|Average coverage of the sequence by the domain:||43.93 %|
|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:||13|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- 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 4 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 P53 domain has been found. There are 206 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...