MEROPS

MEROPS

MEROPS

Overview

The MEROPS database of proteolytic enzymes, their substrates and inhibitors provides a "one-stop shop" for researchers with an interest in proteolytic enzymes. The aim of the database is to provide a classification, a software interface and a bibliography for the retrieval of information about proteolytic enzymes, their substrates and inhibitors, and for the analysis of sequence data. A proteolytic enzyme catalyses the cleavage of a peptide or protein by breaking the peptide bond that exists between amino acids in the chain. The MEROPS classification for peptidases began in 1993. Sequences are grouped into a protein species if they represent the same protein but from different species. For each protein species a type example or holotype is selected, which is usually the protein for which most biochemistry is known. Protein species are grouped into a family if the sequences can be shown to be homologous. Sequence homology can be shown by means of software such as FastA, BlastP and HMMER; to be included in a family a sequence must match an existing member of the family with an expect value of less than 0.001. Because the MEROPS system is a domain classification, the sequence relationship must be within the region identified as the peptidase domain, known as the "peptidase unit". Families are grouped into a clan if the proteins within them share a similar structural fold.

The classification was extended to peptidase inhibitors in 2004. There are six different catalytic types of peptidase, depending on the nature of the nucleophile in the catalytic reaction. Peptidases that use the hydroxyl or thiol group of an amino acid as a nucleophile are known as serine, threonine or cysteine peptidases. Peptidases that use an activated water molecule to hydrolyse a peptide bond are known as aspartic, glutamic or metallo- peptidases, depending on whether the water molecule is bound to aspartic or glutamic acid residues, or to a metal ion. In addition to the peptidases that cleave a peptide bond by hydrolysis, there are also peptide lyases, in which a peptide bond is broken because an asparagine or glutamine residue undergoes a cyclization reaction. There is a unique name for every protein species, family and clan in MEROPS. The first letter of each of these corresponds to the catalytic type: A for aspartic peptidase, C for cysteine peptidase, G for glutamic peptidase, M for metallopeptidase, S for serine peptidase and T for threonine peptidase. In addition, the letter "P" is used for peptidases of mixed catalytic type; the letter "U" is used for peptidases where the catalytic type cannot be determined or is ambiguous; the letter "N" is used for peptide lyases; and the letter "I" is used for peptidase inhibitors.

All proteins are subject to proteolysis, either as a means of activation, de-activation or degradation. In addition to the nomenclature and classification of proteolytic enzymes and peptidase inhibitors, the MEROPS database is also a repository for the known cleavages in peptide, protein and synthetic substrates.

The MEROPS database is also a repository for peptidase-inhibitor interactions. We also a maintain a collection of small-molecule inhibitors, which include naturally occurring and synthetic inhibitors, many of which have important uses in peptidase biochemistry and pharmacology.

In the current release, there are over 500,000 sequences, over 4,600 different peptidases, over 700 different peptidase inhibitors, over 64,000 substrate cleavages, over 6,000 peptidase/inhibitor interactions, and over 59,000 references.

We provide a service analyse sequences and to identify any peptidases or peptidase inhibitors. A user can upload a library of sequences in FastA format and will receive by E-mail a list of peptidase homologues with the MEROPS family and active site residues identified. This service is useful for identifying peptidases in a complete proteome.

We also provide a service to analyse cleaves in proteins to see if the cleavage site is conserved in close homologues. This service is useful for identifying physiologically important cleavages, because these are most likely to be well conserved.

Download and Installation

The database is available through the website. The website can be browsed with Internet Explorer, Firefox or Chrome. To make full use of the molecular structure pages of MEROPS, RASMOL or JMOL is required.

The data are stored in a MySQL database, the tables for which can be downloaded from our FTP site. The FTP site also provides downloads of our sequence collection.

Learn and Support

Please contact merops@sanger.ac.uk for any assistance.

License and Citation

The MEROPS database is provided under the terms of the GNU Library General Public License and the complete content of the database is referred to as the 'Library'.

Contact

Please submit a helpdesk ticket or contact us at merops@sanger.ac.uk for any assistance.

Authors The MEROPS team is Dr Neil D. Rawlings and Dr Alan J. Barrett. The MEROPS team is part of the Protein Families department run by Dr Rob Finn at the EMBL-European Bioinformatics Institute.

Publications

  • Evolutionary families of peptidases.

    Rawlings ND and Barrett AJ

    The Biochemical journal 1993;290 ( Pt 1);205-18

  • Families of serine peptidases.

    Rawlings ND and Barrett AJ

    Methods in enzymology 1994;244;19-61

  • Families of cysteine peptidases.

    Rawlings ND and Barrett AJ

    Methods in enzymology 1994;244;461-86

  • Families of aspartic peptidases, and those of unknown catalytic mechanism.

    Rawlings ND and Barrett AJ

    Methods in enzymology 1995;248;105-20

  • Evolutionary families of metallopeptidases.

    Rawlings ND and Barrett AJ

    Methods in enzymology 1995;248;183-228

  • MEROPS: the peptidase database.

    Rawlings ND and Barrett AJ

    Nucleic acids research 1999;27;1;325-31

  • Dyslipidemia in the elderly: should it be treated?

    Shanmugasundaram M, Rough SJ and Alpert JS

    Clinical cardiology 2010;33;1;4-9

  • Diaphragmatic Breathing.

    Hance IH

    Transactions of the American Climatological and Clinical Association. American Climatological and Clinical Association 1917;33;52-8

  • The MEROPS database as a protease information system.

    Barrett AJ, Rawlings ND and O'Brien EA

    Journal of structural biology 2001;134;2-3;95-102

  • MEROPS: the protease database.

    Rawlings ND, O'Brien E and Barrett AJ

    Nucleic acids research 2002;30;1;343-6

  • A comparison of Pfam and MEROPS: two databases, one comprehensive, and one specialised.

    Studholme DJ, Rawlings ND, Barrett AJ and Bateman A

    BMC bioinformatics 2003;4;17

  • MEROPS: the peptidase database.

    Rawlings ND, Tolle DP and Barrett AJ

    Nucleic acids research 2004;32;Database issue;D160-4

  • Bioinformatics of proteases in the MEROPS database.

    Barrett AJ

    Current opinion in drug discovery & development 2004;7;3;334-41

  • Evolutionary families of peptidase inhibitors.

    Rawlings ND, Tolle DP and Barrett AJ

    The Biochemical journal 2004;378;Pt 3;705-16

  • MEROPS: the peptidase database.

    Rawlings ND, Morton FR and Barrett AJ

    Nucleic acids research 2006;34;Database issue;D270-2

  • 'Species' of peptidases.

    Barrett AJ and Rawlings ND

    Biological chemistry 2007;388;11;1151-7

  • MEROPS: the peptidase database.

    Rawlings ND, Morton FR, Kok CY, Kong J and Barrett AJ

    Nucleic acids research 2008;36;Database issue;D320-5

  • The MEROPS batch BLAST: a tool to detect peptidases and their non-peptidase homologues in a genome.

    Rawlings ND and Morton FR

    Biochimie 2008;90;2;243-59

  • A large and accurate collection of peptidase cleavages in the MEROPS database.

    Rawlings ND

    Database : the journal of biological databases and curation 2009;2009;bap015

  • MEROPS: the peptidase database.

    Rawlings ND, Barrett AJ and Bateman A

    Nucleic acids research 2010;38;Database issue;D227-33

  • Peptidase inhibitors in the MEROPS database.

    Rawlings ND

    Biochimie 2010;92;11;1463-83

  • Asparagine peptide lyases: a seventh catalytic type of proteolytic enzymes.

    Rawlings ND, Barrett AJ and Bateman A

    The Journal of biological chemistry 2011;286;44;38321-8

  • MEROPS: the database of proteolytic enzymes, their substrates and inhibitors.

    Rawlings ND, Barrett AJ and Bateman A

    Nucleic acids research 2012;40;Database issue;D343-50

  • Identification and prioritization of novel uncharacterized peptidases for biochemical characterization.

    Rawlings ND

    Database : the journal of biological databases and curation 2013;2013;bat022

  • MEROPS: the database of proteolytic enzymes, their substrates and inhibitors.

    Rawlings ND, Waller M, Barrett AJ and Bateman A

    Nucleic acids research 2014;42;Database issue;D503-9

  • Using the MEROPS Database for Proteolytic Enzymes and Their Inhibitors and Substrates.

    Rawlings ND, Barrett AJ and Bateman A

    Current protocols in bioinformatics 2014;48;1.25.1-33

Tool Type