The RTKdb is the web-based interface of the RTKdb which is a database containing all the protein sequences of RTK, organized into families. It allows one to select sets of homologous genes from different species (only common species for the moment) and to visualize multiple alignments and phylogenetic trees. Thus the RTKdb is particularly useful for comparative genomics, phylogeny and molecular evolution studies.
The present version of RTKdb is release 0.4 (January 2003). It has been built using sequences from SWISS-PROT 40.40. It contains a total of 159 proteins with the following repartition:
| Homo Sapiens |
51
|
| Mus musculus |
43
|
| Rattus norvegicus |
25
|
| Gallus gallus |
18
|
| Danio rerio |
3
|
| Xenopus laevis |
8
|
| Drosophila melanogaster |
6
|
| Caenorhabditis elegans |
5
|
All the proteins included in this release are classified into 25 families. 19 containing at least two sequences, and 6 are containing unique sequences.
Important note: the SWISS-PROT entries such as those found in RTKdb are copyrighted. They are produced through a collaboration between the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement (See or send an Email tolicense@isb-sib.ch).
The database contains all sequences of common species RTK taken from SWISS-PROT, with alignements, trees, annotation modifications and some hypertext links added who make the specificity of this database and enable you to browse the informations related to a RTK. Each entry lines begins with a two-character line code to classify the information, as in SWISS-PROT. Homologous proteins are classified into families and multiple alignments and phylogenetic trees are computed for each family.
Sequences
The database is built using sequences taken from SWISS-PROT (and in a futur time its annex TrEMBL). The reasons that led us to choose these collections are threefold :
* The SWISS-PROT + TrEMBL set is exhaustive and non-redundant.
* The annotations are of high quality compared to the other general sequence database systems.
* Almost all entries are cross-referenced with their corresponding nucleotide sequences in GenBank / EMBL / DDBJ.
Alignments
For each family, protein sequences are aligned using CLUSTALW 1.7. All the default parameters are used except the "Toggle End Gap Seperation"option, in "Protein Gap parameters" which is turned ON to optimise the alignment of sequences edge.
Phylogenetic trees
The distance used to build the phylogenetic trees is the multiple substitution correction, and they are computed with Clustalw and rooted with preptree.
Receptor tyrosine kinases are transmembrane proteins that have involved for the control and regulation of several key cellular processes during development and in adult-life. They play an essential role in : cell cycle, migration, metabolism, survival, proliferation and cellular differenciation. They belong to the wide tyrosine kinase (TK) family which can be divide into two main groups : cytoplasmic protein (PTK) and transmembrane receptor (RTK). RTK consist of an extracellular ligand-binding region of variable size composed of various domains, a transmembrane hydrophobic domain, and an intracellular region bearing a kinase domain (TK), sometimes split into two parts (TK1 and TK2). The RTK specificity among the various receptors comes from their tyrosine kinase activity induced by binding of the ligand. Based on their structure and ligand-binding specificities, several classes of RTKs have been distinguished in mammals. For exemple, in three classes, the extracellular region is made solely of immunoglobulin-like domains. RTKs are an excellent model for studying evolution of cellular processes in metazoans : first, they represent large families of modular proteins; second, they are major representatives of the intracellular regulatory pathways that are specific of metazoans and third, they belong to the most widespread contingency generating agents of eukaryotic cells : normaly, the protein kinases. Furthermore, because tyrosine kinases have been under close scrutiny for many years in various species, they are associated with a wealth of information, and most of the genes encoding these proteins have probably been identified in mammals; these molecules thus provide a good starting point for comparative studies of multigene families in different species.
Elaboration of a tyrosine kinase receptor database is primarily for the purpose of providing information by collecting knowledge about RTK (genomic and proteic sequences, RTK classification, RTK mutants, phylogenic analyses, multiples alignments, known signaling pathways...), and to give new information obtained from bioinformatics studies on protein and genomic sequences. This work would like to document : a) RTK specific signatures or more conservative sub classes signatures within the tyrosine kinase domain. It could enable discrimination within RTK and between RTK and the other receptors, b) caracteristic patterns that allow detection of new RTK inside complex genomic sequences derived from the sequencing projects. Moreover it allows us to retrieve their phylogenic history. This work needs to share information with other databases : 1) with caracteristic pattern databases to complete their phylogeny story; 2) with EST expression databases to bring about their pattern of expression.
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