The Proteolysis MAP (PMAP) was an integrated web resource focused on

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...

s. Its domain now links to a scam/spam browser extender.

Rationale

PMAP was designed to aid the protease researchers in reasoning about

proteolytic Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Protein degradation is a major regulatory mechanism of gene expression and contributes substantially to shaping mammalian proteomes. Uncatalysed, the hydrolysis o ...

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 ...

History and funding

PMAP was originally created at the

Burnham Institute for Medical Research Sanford Burnham Prebys is a nonprofit biomedical research institute located in La Jolla, California. The institute conducts basic research and translational research focused on human disease. Research at the institute focuses on cancer, neuro ...

, La Jolla, California. In 2004 the

National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...

(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 An enzyme () is a protein that acts as a biological catalyst 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 pro ...

that regulate much of what happens in the

human body The human body is the entire 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 (biology), organs and then Organ system, org ...

, both inside the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

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 chai ...

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, re ...

. Through this activity, they govern the four essential cell functions: differentiation,

motility Motility is the ability of an organism to move independently using metabolism, metabolic energy. This biological concept encompasses movement at various levels, from whole organisms to cells and subcellular components. Motility is observed in ...

, 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 di ...

— 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 thrombus, blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of co ...

. 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 inhibito ...

database.

Goal

Proteolytic pathways, or proteolysis, are the series of events controlled by proteases that occur in response to specific stimuli. The clotting of blood and 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 insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

can be viewed as proteolytic pathways. The activation, regulation and inhibition of the protein are protease reactions to changing

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

levels and trigger 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 Cita ...

. 2007 D546-9 has information on more than 6,600 proteolytic events, and ProfileDB is dedicated to information of the

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 (aquatic environment), the earthy material that exi ...

recognition specificity of proteases. PathwayDB has begun accumulation of

whose function can be dynamically modeled in a rule-based manner. Hypothetical networks are inferred by semi-automated culling from the literature. Protease software tools may help analyze individual proteases and

proteome A 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. P ...

-wide datasets.

Usage

Popular destinations in PMAP are Protease Molecule Pages and Substrate Molecule Pages. Protease Molecule Pages show recent news in

PubMed PubMed is an openly accessible, free database which includes 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 Institute ...

literature of the protease, known

proteolytic events Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Protein degradation is a major regulatory mechanism of gene expression and contributes substantially to shaping mammalian proteomes. Uncatalysed, the hydrolysis o ...

protein domain In molecular biology, a protein domain is a region of a protein's Peptide, polypeptide chain that is self-stabilizing and that Protein folding, folds independently from the rest. Each domain forms a compact folded Protein tertiary structure, thre ...

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, which are the monomers of the polymer. A single amino acid ...

view, as well as a cross annotation in other

bioinformatic Bioinformatics () is an interdisciplinary field of science Science is a systematic discipline that builds and organises knowledge in the form of testable hypotheses and predictions about the universe. Modern science is typically divi ...

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 Protein databases Bioinformatics software Protein domains Protein families Peripheral membrane proteins * * Post-translational modification