The MEROPS Database

Many proteins undergo important post-translational proteolytic processing to remove targeting signals and activation peptides, and most proteins undergo proteolytic inactivation and catabolism. The enzymes that hydrolyse the peptide bonds in proteins and peptides are known as peptidases, proteases or proteolytic enzymes. The MEROPS database ("http://merops.sanger.ac.uk":http://merops.sanger.ac.uk) presents the classification and nomenclature of peptidases, their inhibitors and substrates. In 1993 we proposed the scheme for the classification of peptidases that has been internationally accepted, and in 1996 we established the MEROPS database. Protein inhibitors have been included in the database since 2004. About 2% of the genes in a genome encode peptidase homologues, and a further 1% encode protein inhibitors. For example, the human genome has 1037 genes encoding peptidase homologues (of which 643 are known or predicted to be active peptidases) and 433 protein inhibitor genes (of which 144 have been biochemically characterized as inhibitors). 

The MEROPS classification is hierarchical. Sequences are grouped into a peptidase species (each of which is given a unique identifier, for example C01.060 for cathepsin B); peptidase species are grouped into a family (for example C1); and families grouped into a clan (for example CA). To be included in the same protein species, sequences must be derived from the same node on a dendrogram derived from the family sequence alignment and known (or predicted) to share similar specificity. To be included in the same family sequences must be homologous over the sequence domain that contains the active site residues (peptidases) or reactive site (inhibitors). To be included in the same clan, the proteins must share similar tertiary structures (or the same linear arrangement of active site residues if the structure is unknown). Over 117,000 peptidase homologues are classified into 3114 protein species, 205 families and 52 clans, and 12,104 protein inhibitors are classified into 663 protein species, 64 families and 33 clans.

The database includes manually curated summaries for each clan, family and protein species. There are also sequence alignments and manually curated bibliographies (with over 41,000 references) at every level. In addition to protein inhibitors we also include 158 manually curated summaries for synthetic and naturally occurring small molecule inhibitors. There is also a summary page for each organism listing all known homologues and an analysis highlighting significant presences, absences or gene family expansions for organisms with a completely sequenced genome. 

The MEROPS database includes known peptidase substrates: naturally occurring peptides and proteins, and synthetic substrates. Currently there are 4091 cleavages of synthetic substrates and 95,413 cleavages of proteins (of which 74,740 are physiological). Cleavages in proteins are mapped to UniProt entries. An alignment of very close homologues of each substrate sequence is shown, highlighting residues around each cleavage site indicating whether the peptidase is known to accept the amino acid at that position or not. Cleavage sites that are conserved are likely to be physiological; cleavage sites that are not conserved may be pathological for the species in which they occur or coincidental.

The MEROPS data is freely available to download from our FTP site ("http://ftp.sanger.ac.uk/pub/MEROPS":http://ftp.sanger.ac.uk/pub/MEROPS) and via our Distributed Annotation System (DAS) server ("http://das.sanger.ac.uk/das/merops":http://das.sanger.ac.uk/das/merops).
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Immigrants and Employer-Provided Training

Much has been written about the labour market outcomes for immigrants in their host countries, particularly with regard to earnings, employment and occupational attainment. However, much less attention has been paid to the question of whether immigrants are as likely to receive employer-provided training relative to comparable natives. As such training should be crucial in determining the labour market success of immigrants in the long run it is a critically important question. Using data from a large scale survey of employees in Ireland, we find that immigrants are less likely to receive training from employers, with immigrants from the New Member States of the EU experiencing a particular disadvantage. The immigrant training disadvantage arises in part from a failure on the part of immigrants to get employed by training-oriented firms. However, they also experience a training disadvantage relative to natives within firms where less training is provided.immigrants, employer-provided training, Ireland

Structure/function relationships in the inhibition of thimet oligopeptidase by carboxyphenylpropyl-peptides

AbstractSome novel N-[1(RS)-carboxy-3-phenylpropyl]tripeptide p-aminobenzoates have been synthesised as inhibitors of thimet oligopeptidase (EC 3.4.24.15). These compounds are considered to bind as substrate analogues with the Cpp group in S1 and the peptide portion in the S′ sites. The most potent inhibitor is Cpp-Ala-Pro-Phe-pAb, which has a K1 = 7 nM. Substitution of Gly for Ala at P1′ leads to weaker binding which can be ascribed to increased rotational freedom. Good substrates often have Pro at P2′ and Pro is favoured over Ala at this position in the inhibitors, too. When P2′ is Pro, Phe is preferred over Tyr and Trp in P3′. The p-aminobenzoate group makes an important contribution to the binding, probably by forming a salt bridge, and removal of the C-terminal negative charge results in much less potent inhibitors

MEROPS: the peptidase database

Peptidases (proteolytic enzymes) and their natural, protein inhibitors are of great relevance to biology, medicine and biotechnology. The MEROPS database () aims to fulfil the need for an integrated source of information about these proteins. The organizational principle of the database is a hierarchical classification in which homologous sets of proteins of interest are grouped into families and the homologous families are grouped in clans. The most important addition to the database has been newly written, concise text annotations for each peptidase family. Other forms of information recently added include highlighting of active site residues (or the replacements that render some homologues inactive) in the sequence displays and BlastP search results, dynamically generated alignments and trees at the peptidase or inhibitor level, and a curated list of human and mouse homologues that have been experimentally characterized as active. A new way to display information at taxonomic levels higher than species has been devised. In the Literature pages, references have been flagged to draw attention to particularly ‘hot’ topics

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

BACKGROUND: We wished to compare two databases based on sequence similarity: one that aims to be comprehensive in its coverage of known sequences, and one that specialises in a relatively small subset of known sequences. One of the motivations behind this study was quality control. Pfam is a comprehensive collection of alignments and hidden Markov models representing families of proteins and domains. MEROPS is a catalogue and classification of enzymes with proteolytic activity (peptidases or proteases). These secondary databases are used by researchers worldwide, yet their contents are not peer reviewed. Therefore, we hoped that a systematic comparison of the contents of Pfam and MEROPS would highlight missing members and false-positives leading to improvements in quality of both databases. An additional reason for carrying out this study was to explore the extent of consensus in the definition of a protein family. RESULTS: About half (89 out of 174) of the peptidase families in MEROPS overlapped single Pfam families. A further 32 MEROPS families overlapped multiple Pfam families. Where possible, new Pfam families were built to represent most of the MEROPS families that did not overlap Pfam. When comparing the numbers of sequences found in the overlap between a MEROPS family and its corresponding Pfam family, in most cases the overlap was substantial (52 pairs of MEROPS and Pfam families had an intersection size of greater than 75% of the union) but there were some differences in the sets of sequences included in the MEROPS families versus the overlapping Pfam families. CONCLUSIONS: A number of the discrepancies between MEROPS families and their corresponding Pfam families arose from differences in the aims and philosophies of the two databases. Examination of some of the discrepancies highlighted additional members of families, which have subsequently been added in both Pfam and MEROPS. This has led to improvements in the quality of both databases. Overall there was a great deal of consensus between the databases in definitions of a protein family

Radio Astronomy

Contains reports on two research projects.National Aeronautics and Space Administration (Grant NsG-419)National Aeronautics and Space Administration (Contract NSR-22-009-120)Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force, under Contract DA 28-043-AMC-02536(E)U. S. Navy (Office of Naval Research) under Contract N00014-67-A-0204-0009National Science Foundation (Grant GP-7046

Is there a Wage Premium for Returning Irish Migrants? ESRI WP125. February 2000

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Radio Astronomy

Contains research objectives and reports on one research project.National Aeronautics and Space Administration (Grant NsG-250-62)National Aeronautics and Space Administration (Grant NsG-419)Office of Naval Research (Contract Nonr-3963(02

Radio Astronomy

Contains research objectives and reports on two research projects.National Aeronautics and Space Administration (Grant NsG-250-62)National Aeronautics and Space Administration (Grant NsG-419)U. S. Navy (Office of Naval Research) under Contract Nonr-3963(02)-Task 2Lincoln Laboratory, Purchase Order DDL BB-107U. S. Air Force under Contract AF 19(628)-50