The Proteolysis Map
Encyclopedia
The Proteolysis MAP is an integrated web resource focused on protease
s.
and metabolic pathways.
, La Jolla, California. In 2004 the National Institutes of Health
(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.
, both inside the cell
and out, by cleaving peptide bonds in proteins. Through this activity, they govern the four essential cell functions: differentiation, motility
, division and cell death — and activate important extracellular
episodes, such as the biochemical cascade
effect in blood clotting. Simply stated, life could not exist without them. Extensive on-line classification system for proteases (also referred as peptidases) is deposited in the MEROPS
database.
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
levels and triggering other proteases downstream.
(1)ProteaseDB and (2)SubstrateDB, are driven by an automated annotation pipeline that generates dynamic ‘Molecule Pages’, rich in molecular information. (3)CutDB has information
on more than 6,600 proteolytic events, and (4)ProfileDB is dedicated to information of the substrate
recognition specificity of proteases. (5)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 of the literature. Additionally, protease software tools are available for the analysis of individual proteases and proteome
-wide data sets.
literature of the protease, known proteolytic events, protein domain
location and protein structure
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.
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
s.
Rationale
PMAP is to aid the protease researchers in reasoning about proteolytic networksNeural network
The term neural network was traditionally used to refer to a network or circuit of biological neurons. The modern usage of the term often refers to artificial neural networks, which are composed of artificial neurons or nodes...
and metabolic pathways.
History and funding
PMAP was originally created at the Burnham Institute for Medical ResearchBurnham Institute for Medical Research
The Sanford-Burnham Medical Research Institute, previously Burnham Institute for Medical Research, is a non-profit medical research institute with locations in La Jolla, California, Orlando, Florida, and Santa Barbara, California...
, La Jolla, California. In 2004 the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
(NIH) selected a team led by Jeffrey W. Smith
Jeffrey W. Smith
Jeffrey W. Smith is Director, Program for Excellence in Nanotechnology, Center on Proteolytic Pathways, Tumor Microenvironment at of the Burnham Institute. Jeff earned his Ph.D. in biological sciences at UC Irvine in 1987. Following postdoctoral training at The Scripps Research Institute, he was...
, 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 that regulate much of what happens in the human bodyHuman body
The human body is the entire structure of a human organism, and consists of a head, neck, torso, two arms and two legs.By the time the human reaches adulthood, the body consists of close to 100 trillion cells, the basic unit of life...
, both inside the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
and out, by cleaving peptide bonds in proteins. Through this activity, they govern the four essential cell functions: differentiation, motility
Motility
Motility is a biological term which refers to the ability to move spontaneously and actively, consuming energy in the process. Most animals are motile but the term applies to single-celled and simple multicellular organisms, as well as to some mechanisms of fluid flow in multicellular organs, in...
, division and cell death — and activate important extracellular
Extracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
episodes, such as the biochemical cascade
Biochemical cascade
A biochemical cascade is a series of chemical reactions in which the products of one reaction are consumed in the next reaction. There are several important biochemical cascade reactions in biochemistry, including the enzymatic cascades, such as the coagulation cascade and the complement system,...
effect in blood clotting. 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
Merops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
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 insulinInsulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
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
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
levels and triggering other proteases downstream.
Database content
PMAP integrates five databases (DBs), linked together in one environment.(1)ProteaseDB and (2)SubstrateDB, are driven by an automated annotation pipeline that generates dynamic ‘Molecule Pages’, rich in molecular information. (3)CutDB has information
Information
Information in its most restricted technical sense is a message or collection of messages that consists of an ordered sequence of symbols, or it is the meaning that can be interpreted from such a message or collection of messages. Information can be recorded or transmitted. It can be recorded as...
on more than 6,600 proteolytic events, and (4)ProfileDB is dedicated to information of the substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
recognition specificity of proteases. (5)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 of the literature. Additionally, protease software tools are available for the analysis of individual proteases and proteome
Proteome
The proteome is the entire set of proteins expressed by a genome, cell, tissue or organism. More specifically, it is the set of expressed proteins in a given type of cells or an organism at a given time under defined conditions. The term is a portmanteau of proteins and genome.The term has been...
-wide data sets.
Usage
Popular destinations in PMAP are Protease Molecule Pages and Substrate Molecule Pages. Protease Molecule Pages show recent news in PubMedPubMed
PubMed is a free database accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez information retrieval system...
literature of the protease, known proteolytic events, protein domain
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
location and protein structure
Protein structure
Proteins are an important class of biological macromolecules present in all organisms. Proteins are polymers of amino acids. Classified by their physical size, proteins are nanoparticles . Each protein polymer – also known as a polypeptide – consists of a sequence formed from 20 possible L-α-amino...
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.
See also
- Metabolic pathwayMetabolic pathwayIn biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...
- CytoscapeCytoscapeCytoscape 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...
- Computational genomicsComputational genomicsComputational genomics refers to the use of computational analysis to decipher biology from genome sequences and related data , including both DNA and RNA sequence as well as other "post-genomic" data...
- Metabolic network modellingMetabolic network modellingMetabolic network reconstruction and simulation allows for an in depth insight into comprehending the molecular mechanisms of a particular organism, especially correlating the genome with molecular physiology...
- Protein-protein interaction predictionProtein-protein interaction predictionProtein–protein interaction prediction is a field combining bioinformatics and structural biology in an attempt to identify and catalog physical interactions between pairs or groups of proteins...
- MEROPSMeropsMerops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
External links
- Official website
- Host institution website
- Proteolysis Cut Site database - curated expert annotation from users
- Protease cut sites graphical interface
- Protease cutting predictor
- List of proteases and their specificities
- International Proteolysis Society
- Merops - the peptidase database
- List of protease inhibitors