The Proteolysis Map
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The Proteolysis MAP (PMAP) is an integrated
web resource A web resource is any identifiable resource (digital, physical, or abstract) present on or connected to the World Wide Web.< ...
focused on
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 ...
s.


Rationale

PMAP is to aid the protease researchers in reasoning about
proteolytic Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...
networks Network, networking and networked may refer to: Science and technology * Network theory, the study of graphs as a representation of relations between discrete objects * Network science, an academic field that studies complex networks Mathematics ...
and
metabolic pathways In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical re ...
.


History and funding

PMAP was originally created at the
Burnham Institute for Medical Research Sanford Burnham Prebys is a 501(c)(3) non-profit medical research institute focusing on basic and translational research, with major research programs in cancer, neurodegeneration, diabetes, infectious, inflammatory, and childhood diseases. The ...
, La Jolla, California. In 2004 the
National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
(NIH) selected a team led by Jeffrey W. Smith, to establish the Center on Proteolytic Pathways (CPP). As part of the NIH Roadmap for Biomedical research, the center develops technology to study the behavior of proteins and to disburse that knowledge to the scientific community at large.


Focal point

Proteases are a class of
enzymes Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
that regulate much of what happens in the
human body The human body is the structure of a Human, human being. It is composed of many different types of Cell (biology), cells that together create Tissue (biology), tissues and subsequently organ systems. They ensure homeostasis and the life, viabi ...
, both inside the
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
and out, by cleaving
peptide bonds In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another, along a peptide or protein cha ...
in
proteins 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, respo ...
. Through this activity, they govern the four essential cell functions: differentiation,
motility Motility is the ability of an organism to move independently, using metabolic energy. Definitions Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...
, division and
cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as dis ...
— and activate important
extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
episodes, such as the
biochemical cascade A biochemical cascade, also known as a signaling cascade or signaling pathway, is a series of chemical reactions that occur within a biological cell when initiated by a stimulus. This stimulus, known as a first messenger, acts on a receptor that ...
effect in
blood clotting Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...
. Simply stated, life could not exist without them. Extensive on-line classification system for proteases (also referred as peptidases) is deposited in the
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 inhibitor ...
database.


The goal

Proteolytic pathways, or proteolysis, are the series of events controlled by proteases that occur in response to specific stimuli. In addition to the clotting of blood, the production of
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
can be viewed as a proteolytic pathway, as the activation, regulation and inhibition of that protein is the result of proteases reacting to changing
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
levels and triggering other proteases downstream.


Database content

PMAP integrates five databases. ProteaseDB and SubstrateDB, are driven by an automated annotation pipeline that generates dynamic ‘Molecule Pages’, rich in molecular information. CutDBIgarashi Y, Eroshkin A, Gramatikova S, Gramatikoff K, Zhang Y, Smith JW, Osterman AL, Godzik A. CutDB: a proteolytic event database.
Nucleic Acids Research ''Nucleic Acids Research'' is an open-access peer-reviewed scientific journal published since 1974 by the Oxford University Press. The journal covers research on nucleic acids, such as DNA and RNA, and related work. According to the ''Journal Cit ...
. 2007 D546-9
has information on more than 6,600 proteolytic events, and ProfileDB is dedicated to information of the substrate recognition specificity of proteases. PathwayDB, just begun accumulation of
metabolic pathways In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical re ...
whose function can be dynamically modeled in a rule-based manner. Hypothetical networks are inferred by semi-automated culling from the literature. Additionally, protease software tools are available for the analysis of individual proteases and
proteome The proteome is the entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time. It is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. ...
-wide data sets.


Usage

Popular destinations in PMAP are Protease Molecule Pages and Substrate Molecule Pages. Protease Molecule Pages show recent news in
PubMed PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine (NLM) at the National Institutes of Health maintain the ...
literature of the protease, known
proteolytic events Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...
,
protein domain In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...
location and
protein structure Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, the monomers of the polymer. A single amino acid monomer ma ...
view, as well as a cross annotation in other
bioinformatic Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combine ...
databases section. Substrate Molecule Pages display protein domains and experimentally derived protease cut-sites for a given protein target of interest.


See also

*
Cytoscape Cytoscape is an open source bioinformatics software platform for visualizing molecular interaction networks and integrating with gene expression profiles and other state data. Additional features are available as plugins. Plugins are availabl ...
*
Computational genomics Computational genomics refers to the use of computational and statistical analysis to decipher biology from genome sequences and related data, including both DNA and RNA sequence as well as other "post-genomic" data (i.e., experimental data obtai ...
*
Metabolic network modelling Metabolic network modelling, also known as metabolic network reconstruction or metabolic pathway analysis, allows for an in-depth insight into the molecular mechanisms of a particular organism. In particular, these models correlate the genome wi ...
* Protein-protein interaction prediction


References


External links

*
Official website

Proteolysis Cut Site database - curated expert annotation from users

Protease cut sites graphical interface

Protease cutting predictor

Merops - the peptidase database
{{DEFAULTSORT:Proteolysis Map Molecular biology Biological databases Bioinformatics software Systems biology Mathematical and theoretical biology Protein domains Protein families Peripheral membrane proteins * * Post-translational modification Programmed cell death Apoptosis