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  Acknowledgement  
     
     
The details of our curation/data preparation processes for each of the category are as follow:
 
Isoforms
 
Isoform details are curated from published literatures documenting them. The literature references can be found in each of the detail page.
 
Mutations
 

Please note that ongoing efforts are in place to download new datasets from the following sources. Manual curation is also involved to remove duplicate mutation entries.

IARC TP53 Mutation Database

Datasets of Somatic Mutations and Germline Mutations were downloaded from IARC TP53 Mutation Database (version of database downloaded: R11).

Users of the knowledgebase should refer to the Disclaimer for IARC.

Data Processing

The following IARC records were excluded from the knowledgebase:

  1. Records without PubMed IDs.
  2. Records with ambiguous information, such as
    • deletion records without known number of nucleotides deleted,
    • intron mutations without exact nucleotide mutation positions,
    • records which are inconsistent with respect to the reference p53 nucleotide sequence (GenBank Accession Number X54156).

IARC mutation data is represented as follows:

  1. Information on block deletions is stored with start and end nucleotide positions. Hence, the mutation frequencies include deletions that are found within these deletion blocks. For example, a deletion of 9bps starting from nucleotide position 14,492 (codon 275) includes all records of deletions found in codons 275, 276 and 277.
  2. Tandem mutations are concurrent mutations found on consecutive nucleotide positions. For such mutations, information on the start and end nucleotide positions correspond to the first and second nucleotide positions of the mutation record.
  3. Changes were made to the following 'Mutation Types':
    • “G:C > T:A at CpG” is changed to “G:C > T:A”,
    • “CC tandem” is changed to “Tandem”.

*Note : The mutation frequencies generated by the knowledgebase differs from IARC's because of different data representations (refer to FAQ).

Given the possibility of errors that could arise from the simple merger of datasets from the IARC and T. Soussi web sites, we are in the process of reviewing how best to incorporate correctly information from these two sources. As such, we are only using data from IARC for a start until this issue is resolved.

 
 
Polymorphisms
 

The p53 polymorphism data were obtained from five resources, i.e. The International HapMap Project, Perlegen Science, NIEHS (National Institute of Environmental Health Sciences), IARC (International Agency for Research on Cancer) and other published literatures documenting them.

Users of the p53 Knowledgebase should refer to:

The HapMap, Perlegen and NIEHS are online databases for polymorphism and genotyping data of several populations. Information such as the location, alleles, frequencies and the population were extracted from these online databases. For the NIEHS data, a location is considered polymorphic only if the minor allele frequency is at least 1%. All the polymorphism data are mapped to the reference p53 nucleotide sequence (GenBank Accession Number X54156).

In addition to the information above, functional positions of the polymorphic site (whether they are intronic, synonymous, non-synonymous or untranslated) were also checked. Furthermore, short descriptions such as deletion, insertion, or ambiguity were given.

The IARC data and other literature served as additional sources for polymorphism data, such as alleles and positions. Information such as the population and allelic frequencies were supplemented from other databases whenever available.

Besides the polymorphism data, disease association relating to the polymorphism site were also curated. Disease association information include disease name, population studied, association ("Yes" or "No"), additional remarks and the literature references.
 
Haplotypes
 

The p53 haplotypes were inferred from the International HapMap Project's data using HapBlock. HapBlock was used for block reconstruction as it is free for academic use and provides several haplotype block and tag SNP definitions.

Users of the p53 Knowledgebase should refer to HapMap's Guidelines for Data Use and HapBlock's Terms of Usage.

Genotyping data, frequency information, and general pedigree information for the Caucasian and the African population is required for inferring the haplotypes. Currently, the 50 kb upstream and 50 kb downstream regions of the p53 gene were included for the inference and display of haplotype blocks across the p53 gene.

Child information from the Caucasian and African populations were excluded from the inference. In addition, SNPs with minor allele frequency less than 5% were removed. Haploytype blocks were inferred using the LD based method as described by Gabriel et. al. and tag SNP definition by using r2 measurement as described by Carlson et. al.

 
p53-Related Molecules
 

p53-related molecules data such as their SWISSPROT ID, Entrez Gene ID, Gene Ontology, KEGG pathways, Interpro entry, Pfam entry and PDB entries was obtained from the molecule's UCSC genome browser's entry. Additional information such as the Homologene ID and the BIND interaction between the molecule and p53 was also included from their respective sources.

Users of the p53 Knowledgebase should refer to the following:
 
Transcription Factors
 

Transcription factors information was curated from online databases (TRED, TRANSFAC, BIND, BioCarta and KEGG) and other published literatures documenting them (Only data from experiments using human cell cultures were considered). Data pertaining to p53 promoters was obtained from TRED and TRANSFAC whereas data pertaining to proteins interacting with transcription factors of p53 was obtained from BIND and BioCarta. Pathway information involving the transcription factors of p53 was obtained from KEGG.

Users of the p53 Knowledgebase should refer to the following:
 
Transcriptional Targets
 

Target genes information was curated from online databases (TRANSFAC) and other published literatures documenting them. Binding site sequences were extracted for each target gene from published literatures and their nucleotide positions verified using the UCSC Genome Browser's May 2004 assembly. The official symbol for target gene is obtained from Entrez Genes. Additional relevant journal references, if any, are taken from Bibliography section. Additional binding site information, if any, is obtained by following links to BIND in the Interactions section.

Users of the p53 Knowledgebase should refer to the following:

 
Protein Interactions
 

The protein interaction section of the Knowledgebase aims to give a comprehensive coverage of all human proteins, human protein complexes, viral proteins and small molecules interacting with p53 protein in human. The interactions include protein-protein bindings and post-translational modifications (phosphorylation, NEDDylation, ubiquitination, etc).

The p53 protein interaction data is taken from AfCS-Nature Signaling Gateway. It consists of BIND records with supporting literatures. Each protein interaction record in the Knowledgebase corresponds to a single molecule (protein , protein complex or small molecule) that interacts with the human p53 protein. These records are supported by at least one experimental result as documented in published literatures.

BIND records referring to the same interaction and were merged into a single record. Information on experimental systems, techniques and binding sites were verified with the cited literature before being included into our database. Extra information such as cause and regulation of interaction as well as molecular, physiological and localization effects resulting from the interactions (which are not found in the AfCS-Nature Signaling Gateway and BIND) were also curated from the published literatures.

Users of the p53 Knowledgebase should refer to the following:

 
Monoclonal Antibodies
 

Information on the p53 antibodies was primarily obtained from Dr. Borivoj Vojtesek, Institute of Molecular and Cell Biology.
 
Modifications
 

Post Translational Modifications details were curated from published literatures documenting them. The literature references can be found in each of the detail page.

 
Regulatory Pathways
 

The p53 Regulatory Pathways page aims to consolidate information from various public and commercial data sources with relevance to the p53 molecule and its pathways. This page consists of the following sections:

This section centers on the p53 core regulatory network, constructed based on a review article by Harris and Levine (2005). This network is a summary of positive and negative feedback loops involving p53 and is described in more detail in the book chapter written by members of the BioPathways Group at BII (Aguda et al., 2005). Data in this section was obtained by doing searches from the commercially available Pathway Assist software. For each interaction shown in the core network, a search of direct interactions was performed. Pathway Assist returns a network diagram of biological associations from the ResNet database.

  • Pathway Maps Online:

This section contains pathways obtained from public databases. The pathways listed in this page are those that involve p53 and provide links directly to the relevant public database. Listed below are the databases from which links are provided:

Users of the p53 Knowledgebase should refer to:

  • Pathway Resources:

This section is a list of links to resources that may be useful for those doing pathways analysis.
 
PDB Structures
 

The PDB Structure section includes all the experimentally solved RCSB's PDB structures that contain at least part of the human p53 protein. Data extracted for each PDB entry includes:

  • The complex partner of the p53 peptide in the structure
  • Chains in which the p53 peptides are located.
  • Mutation information about the p53 protein in the structure.
  • The annotation of the PDB entry from RCSB's beta site.
  • PubMed ID of the literature.

The start and end amino acid positions of the p53 peptide in each structure was further verified by aligning the peptide sequence with the full-length p53 sequence.

Users of the p53 Knowledgebase should refer to RCSB PDB's Advisory Notice.
 
References
 
 
   
 
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