The Proteolysis MAP (PMAP) is an integrated web resource 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 ...

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 prote ...

networks and metabolic pathways.

History and funding

PMAP was originally created at the Burnham Institute for Medical Research, 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 lat ...

(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 substrates, and the enzyme converts the substrates into different molecules known as products. ...

that regulate much of what happens in the

human body The human body is the structure of a human being. It is composed of many different types of cells that together create tissues and subsequently organ systems. They ensure homeostasis and the viability of the human body. It comprises a hea ...

, both inside the cell and out, by cleaving peptide bonds 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 — 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 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 mechan ...

. 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 inhibitors ...

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 ...

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, u ...

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. 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 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-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 maintai ...

literature of the protease, known proteolytic events,

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 ...

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 monom ...

view, as well as a cross annotation in other bioinformatic databases section. Substrate Molecule Pages display protein domains and experimentally derived protease cut-sites for a given protein target of interest.

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