TopFIND is the Termini oriented protein Function Inferred Database (TopFIND) is an integrated knowledgebase focused on

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

termini, their formation by

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the form ...

s and functional implications. It contains information about the processing and the processing state of proteins and functional implications thereof derived from research literature, contributions by the scientific community and biological

database In computing, a database is an organized collection of data stored and accessed electronically. Small databases can be stored on a file system, while large databases are hosted on computer clusters or cloud storage. The design of databases spa ...

Background

Among the most fundamental characteristics of a

are the N- and C-termini defining the start and end of the

polypeptide chain Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides ...

. While genetically encoded, protein termini isoforms are also often generated during

translation Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...

, following which, termini are highly dynamic, being frequently trimmed at their ends by a large array of exopeptidases. Neo-termini can also be generated by endopeptidases after precise and limited proteolysis, termed processing. Necessary for the maturation of many proteins, processing can also occur afterwards, often resulting in dramatic functional consequences. Aberrant proteolysis can cause wide range of diseases like arthritis or cancer. Hence, proteolytic generation of pleiotrophic stable forms of proteins, the universal susceptibility of proteins to proteolysis, and its irreversibility, distinguishes proteolysis from many highly studied posttranslational modifications. Proteases are tightly interconnected in the protease web and their aberrant activity in disease can lead to diagnostic fragment profiles with characteristic protein termini. Following proteolysis, the newly formed protein termini can be further modified, a process that affects protein function and stability.

Knowledgebase content

TopFIND is a resource for comprehensive coverage of protein N- and C-termini discovered by all available in silico, in vitro as well as in vivo methodologies. It makes use of existing knowledge by seamless integration of data from

UniProt UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains a large amount of information about the biological function of proteins derived fro ...

and

MEROPS MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. The classification scheme for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibi ...

and provides access to new data from community submission and manual literature curating. It renders modifications of

termini, such as acetylation and citrullination, easily accessible and searchable and provides the means to identify and analyse extend and distribution of terminal modifications across a protein. Since its inception TopFIND has been expanded to further species.

Data access

The data is presented to the user with a strong emphasis on the relation to curated background information and underlying evidence that led to the observation of a terminus, its modification or proteolytic cleavage. In brief the

information, its domain structure, protein termini, terminus modifications and proteolytic processing of and by other proteins is listed. All information is accompanied by metadata like its original source, method of identification, confidence measurement or related publication. A positional cross correlation evaluation matches termini and cleavage sites with protein features (such as amino acid variants) and domains to highlight potential effects and dependencies in a unique way. Also, a network view of all proteins showing their functional dependency as

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (locomotion), the surface over which an organism lo ...

or protease inhibitor tied in with protein interactions is provided for the easy evaluation of network wide effects. A powerful yet user friendly filtering mechanism allows the presented data to be filtered based on parameters like methodology used, in vivo relevance, confidence or data source (e.g. limited to a single laboratory or publication). This provides means to assess physiological relevant data and to deduce functional information and hypotheses relevant to the bench scientist. In a later release analysis tools for the evaluation of proteolytic pathways in experimental data have been added.

References

External links

TopFIND - main website and web interface

Host institution website

Research group of Philipp Lange - inventor & core developer

Research Group of Christopher Overall - home of TopFIND

Merops - the peptidase database

UniProt
* {{Proteases Molecular biology Biological databases Bioinformatics software Systems biology Mathematical and theoretical biology Protein domains Protein families Post-translational modification

Background

Knowledgebase content

Data access

See also

References

External links