The Proteolysis Map

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The Proteolysis MAP (PMAP) was an integrated web resource focused on proteases. [1] Its domain now links to a scam/spam browser extender.

Contents

Rationale

PMAP was designed to aid the protease researchers in reasoning about proteolytic 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 (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 that regulate much of what happens in the human body, 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. Life could not exist without them. Extensive on-line classification system for proteases (also referred as peptidases) is deposited in the MEROPS 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 can be viewed as proteolytic pathways. The activation, regulation and inhibition of the protein are protease reactions to changing glucose 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. CutDB [2] has information on more than 6,600 proteolytic events, and ProfileDB is dedicated to information of the substrate recognition specificity of proteases. PathwayDB has 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. Protease software tools may help analyze individual proteases and proteome-wide datasets.

Usage

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

See also

Related Research Articles

<span class="mw-page-title-main">Proteolysis</span> Breakdown of proteins into smaller polypeptides or amino acids

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, but may also occur by intra-molecular digestion.

<span class="mw-page-title-main">Protease</span> Enzyme that cleaves other proteins into smaller peptides

A protease is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do this by cleaving the peptide bonds within proteins by hydrolysis, a reaction where water breaks bonds. Proteases are involved in many biological functions, including digestion of ingested proteins, protein catabolism, and cell signaling.

<span class="mw-page-title-main">Thrombin</span> Enzyme involved in blood coagulation in humans

Thrombin is a serine protease, an enzyme that, in humans, is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the clotting process. Thrombin in turn acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions.

In biology and biochemistry, protease inhibitors, or antiproteases, are molecules that inhibit the function of proteases. Many naturally occurring protease inhibitors are proteins.

<span class="mw-page-title-main">Serine protease</span> Class of enzymes

Serine proteases are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. Serine proteases fall into two broad categories based on their structure: chymotrypsin-like (trypsin-like) or subtilisin-like.

A metalloproteinase, or metalloprotease, is any protease enzyme whose catalytic mechanism involves a metal. An example is ADAM12 which plays a significant role in the fusion of muscle cells during embryo development, in a process known as myogenesis.

<span class="mw-page-title-main">Calpain</span> Protease enzyme present in mammals and other organisms

A calpain is a protein belonging to the family of calcium-dependent, non-lysosomal cysteine proteases expressed ubiquitously in mammals and many other organisms. Calpains constitute the C2 family of protease clan CA in the MEROPS database. The calpain proteolytic system includes the calpain proteases, the small regulatory subunit CAPNS1, also known as CAPN4, and the endogenous calpain-specific inhibitor, calpastatin.

<span class="mw-page-title-main">Cysteine protease</span> Class of enzymes

Cysteine proteases, also known as thiol proteases, are hydrolase enzymes that degrade proteins. These proteases share a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic triad or dyad.

In molecular biology, the Signal Peptide Peptidase (SPP) is a type of protein that specifically cleaves parts of other proteins. It is an intramembrane aspartyl protease with the conserved active site motifs 'YD' and 'GxGD' in adjacent transmembrane domains (TMDs). Its sequences is highly conserved in different vertebrate species. SPP cleaves remnant signal peptides left behind in membrane by the action of signal peptidase and also plays key roles in immune surveillance and the maturation of certain viral proteins.

<span class="mw-page-title-main">Aspartic protease</span>

Aspartic proteases are a catalytic type of protease enzymes that use an activated water molecule bound to one or more aspartate residues for catalysis of their peptide substrates. In general, they have two highly conserved aspartates in the active site and are optimally active at acidic pH. Nearly all known aspartyl proteases are inhibited by pepstatin.

Caspase 5 is an enzyme that proteolytically cleaves other proteins at an aspartic acid residue, and belongs to a family of cysteine proteases called caspases. It is an inflammatory caspase, along with caspase 1, caspase 4 and the murine caspase 4 homolog caspase 11, and has a role in the immune system.

MEROPS is an online database for peptidases and their inhibitors. The classification scheme for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibitors by Rawlings et al. in 2004. The most recent version, MEROPS 12.4, was released in late October 2021.

<span class="mw-page-title-main">Caspase 7</span> Protein-coding gene in the species Homo sapiens

Caspase-7, apoptosis-related cysteine peptidase, also known as CASP7, is a human protein encoded by the CASP7 gene. CASP7 orthologs have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.

<span class="mw-page-title-main">ATP-dependent Clp protease proteolytic subunit</span> Protein-coding gene in the species Homo sapiens

ATP-dependent Clp protease proteolytic subunit (ClpP) is an enzyme that in humans is encoded by the CLPP gene. This protein is an essential component to form the protein complex of Clp protease.

<span class="mw-page-title-main">Short linear motif</span>

In molecular biology short linear motifs (SLiMs), linear motifs or minimotifs are short stretches of protein sequence that mediate protein–protein interaction.

TopFIND is the Termini oriented protein Function Inferred Database (TopFIND) is an integrated knowledgebase focused on protein termini, their formation by proteases 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 databases.

Terminal amine isotopic labeling of substrates (TAILS) is a method in quantitative proteomics that identifies the protein content of samples based on N-terminal fragments of each protein and detects differences in protein abundance among samples.

<span class="mw-page-title-main">PA clan of proteases</span>

The PA clan is the largest group of proteases with common ancestry as identified by structural homology. Members have a chymotrypsin-like fold and similar proteolysis mechanisms but can have identity of <10%. The clan contains both cysteine and serine proteases. PA clan proteases can be found in plants, animals, fungi, eubacteria, archaea and viruses.

<span class="mw-page-title-main">Degradomics</span> Sub-discipline of biology

Degradomics is a sub-discipline of biology encompassing all the genomic and proteomic approaches devoted to the study of proteases, their inhibitors, and their substrates on a system-wide scale. This includes the analysis of the protease and protease-substrate repertoires, also called "protease degradomes". The scope of these degradomes can range from cell, tissue, and organism-wide scales.

Asparagine peptide lyase are one of the seven groups in which proteases, also termed proteolytic enzymes, peptidases, or proteinases, are classified according to their catalytic residue. The catalytic mechanism of the asparagine peptide lyases involves an asparagine residue acting as nucleophile to perform a nucleophilic elimination reaction, rather than hydrolysis, to catalyse the breaking of a peptide bond.

References

  1. Igarashi, Y; Heureux, E; Doctor, KS; Talwar, P; Gramatikova, S; Gramatikoff, K; Zhang, Y; Blinov, M; Ibragimova, SS; Boyd, S; Ratnikov, B; Cieplak, P; Godzik, A; Smith, JW; Osterman, AL; Eroshkin, AM (2008). "PMAP: databases for analyzing proteolytic events and pathways". Nucleic Acids Research . 37 (Database issue): D611–D618. doi:10.1093/nar/gkn683. PMC   2686432 . PMID   18842634.
  2. Igarashi 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