CoChat
Sign Up
Cited by 1,749Protease and Inhibitor MechanismsGenomics and Phylogenetic StudiesEnzyme Structure and Function

The MEROPS database of proteolytic enzymes, their substrates and inhibitors in 2017 and a comparison with peptidases in the PANTHER database

Open access
Rawlings, Neil D, Barrett, Alan J, Thomas, Paul D, Huang, Xiaosong, Bateman, Alex, Finn, Robert D·2018·Nucleic Acids Research
DOI 10.1093/nar/gkx1134PMC PMC5753285
Open this paper in CoChat — free accountOpen PDF

Abstract

The MEROPS database (http://www.ebi.ac.uk/merops/) is an integrated source of information about peptidases, their substrates and inhibitors. The hierarchical classification is: protein-species, family, clan, with an identifier at each level. The MEROPS website moved to the EMBL-EBI in 2017, requiring refactoring of the code-base and services provided. The interface to sequence searching has changed and the MEROPS protein sequence libraries can be searched at the EMBL-EBI with HMMER, FastA and BLASTP. Cross-references have been established between MEROPS and the PANTHER database at both the family and protein-species level, which will help to improve curation and coverage between the resources. Because of the increasing size of the MEROPS sequence collection, in future only sequences of characterized proteins, and from completely sequenced genomes of organisms of evolutionary, medical or commercial significance will be added. As an example, peptidase homologues in four proteomes from the Asgard superphylum of Archaea have been identified and compared to other archaean, bacterial and eukaryote proteomes. This has given insights into the origins and evolution of peptidase families, including an expansion in the number of proteasome components in Asgard archaeotes and as organisms increase in complexity. Novel structures for proteasome complexes in archaea are postulated.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/nar/gkx1134

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Overall selectivity of individually synthesised tetrapeptide pNA substrates roughly follows the HNE consensus cleavage sequence in the MEROPS database.

    “Overall, selectivity for these individually synthesised peptides roughly follows the HNE consensus cleavage sequence found in the MEROPS database [28] shown in Figure 1B.”

    From Discrimination of Methionine Sulfoxide and Sulfone by Human Neutrophil Elastase (2021) · cites this paper as [28]

    The Introduction (page unavailable) says MEROPS contains known cleavage sites for proteins, peptides and synthetic substrates, supporting its use as a source of cleavage data. Our copy does not give an HNE consensus sequence or compare it with the citing authors’ tetrapeptide results, so the specific agreement claimed cannot be verified from this paper. (LLM, conf=0.79)

    Experimental — accuracy not yet measured

  • The HNE consensus cleavage sequences of flagellin (E163MSA) and OmpA (G141MLS) contain oxidisable methionine residues.

    “Both of these targets have consensus cleavage sequences defined in the MEROPS database for HNE that contain oxidisable methionine residues (Flagellin E163MSA, OmpA G141MLS) [28].”

    From Discrimination of Methionine Sulfoxide and Sulfone by Human Neutrophil Elastase (2021) · cites this paper as [28]

    The Introduction states that MEROPS contains a collection of known substrate cleavage sites. Our copy does not identify HNE cleavage sequences for flagellin or OmpA, give E163MSA or G141MLS, or discuss methionine oxidation; searches for those terms found no matching passage. It supports the database attribution generally, but not the specific sequences. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 25

  1. [1]Rawlings N.D., Barrett A.J. Evolutionary families of peptidases. Biochem. J. 1993; 290: 205– 218. 8439290 PMC1132403
  2. [2]Rawlings N.D., Tolle D.P., Barrett A.J. Evolutionary families of peptidase inhibitors. Biochem. J. 2004; 378: 705– 716. 14705960 PMC1224039
  3. [3]Barrett A.J., Rawlings N.D. ‘Species’ of peptidases. Biol. Chem. 2007; 388: 1151– 1157. 17976007
  4. [4]Rawlings N.D., Barrett A.J., Bateman A. Asparagine peptide lyases: a seventh catalytic type of proteolytic enzymes. J. Biol. Chem. 2011; 286: 38321– 38328. 21832066 PMC3207474
  5. [5]Rawlings N.D. A large and accurate collection of peptidase cleavages in the MEROPS database. Database (Oxford). 2009; 2009: bap015. 20157488 PMC2790309
  6. [6]Rawlings N.D., Morton F.R., Kok C.Y., Kong J., Barrett A.J. MEROPS: the peptidase database. Nucleic Acids Res. 2008; 36: D320– D325. 17991683 PMC2238837
  7. [7]Finn R.D., Coggill P., Eberhardt R.Y., Eddy S.R., Mistry J., Mitchell A.L., Potter S.C., Punta M., Qureshi M., Sangrador-Vegas A. The Pfam protein families database: towards a more sustainable future. Nucleic Acids Res. 2016; 44: D279– D285. 26673716 PMC4702930
  8. [8]UniProt Consortium UniProt: the universal protein knowledgebase. Nucleic Acids Res. 2017; 45: D158– D169. 27899622 PMC5210571
  9. [9]NCBI Resource Coordinators Database Resources of the National Center for Biotechnology Information. Nucleic Acids Res. 2017; 45: D12– D17. 27899561 PMC5210554
  10. [11]Finn R.D., Clements J., Arndt W., Miller B.L., Wheeler T.J., Schreiber F., Bateman A., Eddy S.R. HMMER web server: 2015 update. Nucleic Acids Res. 2015; 43: W30– W38. 25943547 PMC4489315
  11. [12]Edgar R.C. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004; 32: 1792– 1797. 15034147 PMC390337
  12. [13]Howe K., Bateman A., Durbin R. QuickTree: building huge Neighbour-Joining trees of protein sequences. Bioinformatics. 2002; 18: 1546– 1547. 12424131
  13. [14]Tieku S., Hooper N.M. Inhibition of aminopeptidases N, A and W. A re-evaluation of the actions of bestatin and inhibitors of angiotensin converting enzyme. Biochem. Pharmacol. 1992; 44: 1725– 1730. 1360211 PMC7111144
  14. [15]Rawlings N.D., Barrett A.J., Bateman A. Using the MEROPS Database for Proteolytic Enzymes and Their Inhibitors and Substrates. Curr. Protoc. Bioinformatics. 2014; 48: 1.25.1– 33. 25501939
  15. [16]Mi H., Muruganujan A., Thomas P.D. PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees. Nucleic Acids Res. 2013; 41: D377– D386. 23193289 PMC3531194
  16. [17]Katoh K., Standley D.M. MAFFT: iterative refinement and additional methods. Methods Mol. Biol. 2014; 1079: 131– 146. 24170399
  17. [18]Thomas P.D. GIGA: a simple, efficient algorithm for gene tree inference in the genomic age. BMC Bioinformatics. 2010; 11: 312. 20534164 PMC2905364
  18. [19]Rawlings N.D., Morton F.R. The MEROPS batch BLAST: a tool to detect peptidases and their non-peptidase homologues in a genome. Biochimie. 2008; 90: 243– 259. 17980477
  19. [20]Rose P.W., Prlić A., Altunkaya A., Bi C., Bradley A.R., Christie C.H., Costanzo L.D., Duarte J.M., Dutta S., Feng Z. The RCSB protein data bank: integrative view of protein, gene and 3D structural information. Nucleic Acids Res. 2017; 45: D271– D281. 27794042 PMC5210513
  20. [21]Velankar S., van Ginkel G., Alhroub Y., Battle G.M., Berrisford J.M., Conroy M.J., Dana J.M., Gore S.P., Gutmanas A., Haslam P. PDBe: improved accessibility of macromolecular structure data from PDB and EMDB. Nucleic Acids Res. 2016; 44: D385– D395. 26476444 PMC4702783
  21. [22]Laskowski R.A., Jabłońska J., Pravda L., Vařeková R.S., Thornton J.M. PDBsum: Structural summaries of PDB entries. Protein Sci. 2017; doi:10.1002/pro.3289. PMC5734310 28875543 · DOI
  22. [25]Ferla M.P., Thrash J.C., Giovannoni S.J., Patrick W.M. New rRNA gene-based phylogenies of the Alphaproteobacteria provide perspective on major groups, mitochondrial ancestry and phylogenetic instability. PLoS One. 2013; 8: e83383. 24349502 PMC3859672
  23. [26]Sousa M.C., Trame C.B., Tsuruta H., Wilbanks S.M., Reddy V.S., McKay D.B. Crystal and solution structures of an HslUV protease-chaperone complex. Cell. 2000; 103: 633– 643. 11106733
  24. [27]Löwe J., Stock D., Jap B., Zwickl P., Baumeister W., Huber R. Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution. Science. 1995; 268: 533– 539. 7725097
  25. [28]Groll M., Ditzel L., Löwe J., Stock D., Bochtler M., Bartunik H.D., Huber R. Structure of 20S proteasome from yeast at 2.4 A resolution. Nature. 1997; 386: 463– 471. 9087403

Cited by

Sorted by citations

Authors
Rawlings, N. D., Barrett, A. J., Thomas, P. D., Huang, X., Bateman, A., & Finn, R. D.
Affiliations
  • European Bioinformatics Institute (GB)
  • University of Southern California (US)
Corresponding author
Rawlings, Neil D
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2017-11-14
Volume
46
Issue
D1
Pages
D624-D632
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkx1134
PMC
PMC5753285
OpenAlex
W2769449671
Cited by
1,749
References
3
Citations by year
2026: 158 · 2025: 189 · 2024: 246 · 2023: 253 · 2022: 248 · 2021: 242 · 2020: 206 · 2019: 157 · 2018: 45 · 2017: 2 · 2016: 1
FWCI
37.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation (1458808)
  • Wellcome Trust
  • European Bioinformatics Institute
  • Research Councils UK
  • Directorate for Biological Sciences
  • Biotechnology and Biological Sciences Research Council (BB/N00521X/1)
  • National Human Genome Research Institute (U41HG002273)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
proteolytic enzymes, enzyme substrates, enzyme inhibitors, protein family classification, Asgard archaea, database refactoring
MeSH terms
Archaea, Bacteria, Humans, Peptide Hydrolases, Phylogeny, Protease Inhibitors, Substrate Specificity, Sequence Alignment, Databases, Protein, Eukaryota

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review