Evidence map›Paper›PMID 33727531›Full record

ArticleNature communications2021

Mapping specificity, cleavage entropy, allosteric changes and substrates of blood proteases in a high-throughput screen.

Federico Uliana, Matej Vizovišek, Laura Acquasaliente, Rodolfo Ciuffa, Andrea Fossati, Fabian Frommelt, Sandra Goetze, Bernd Wollscheid, Matthias Gstaiger, Vincenzo De Filippis and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 36 citations in OpenAlex.

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  4. The main protease (MCommunications biology · 2025
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  9. Thrombin has dual trypsin-like and chymotrypsin-like specificity.Journal of thrombosis and haemostasis : JTH · 2024
    Article
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  15. Adhesive Virulence Factors ofACS bio & med chem Au · 2022
    Article
  16. Comparative sequence analysis of vitamin K-dependent coagulation factors.Journal of thrombosis and haemostasis : JTH · 2022
    Article
  17. Article
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  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 3 countries.

Federico Uliana *Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
Matej Vizovišek *Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
Laura AcquasalienteDepartment of Pharmaceutical and Pharmacological Sciences, Laboratory of Protein Chemistry and Molecular Hematology, University of Padua, Padua, Italy.ORCID 0000-0001-6495-0871
Rodolfo CiuffaDepartment of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
Andrea FossatiDepartment of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.ORCID 0000-0001-5170-4903
Fabian FrommeltDepartment of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.ORCID 0000-0003-3666-8005
Sandra GoetzeDepartment of Health Sciences and Technology, Institute of Translational Medicine, ETH Zürich, Zürich, Switzerland.ORCID 0000-0001-6880-8020
Bernd WollscheidDepartment of Health Sciences and Technology, Institute of Translational Medicine, ETH Zürich, Zürich, Switzerland.
Matthias GstaigerDepartment of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.ORCID 0000-0002-3245-3253
Vincenzo De FilippisDepartment of Pharmaceutical and Pharmacological Sciences, Laboratory of Protein Chemistry and Molecular Hematology, University of Padua, Padua, Italy.ORCID 0000-0001-9775-8894
Ulrich Auf dem KellerDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
Ruedi AebersoldDepartment of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland. aebersold@imsb.biol.ethz.ch.ORCID 0000-0002-9576-3267
ETH Zurich · CHSIB Swiss Institute of Bioinformatics · CHUniversity of Padua · ITTechnical University of Denmark · DKUniversity of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proteases are among the largest protein families and critical regulators of biochemical processes like apoptosis and blood coagulation. Knowledge of proteases has been expanded by the development of proteomic approaches, however, technology for multiplexed screening of proteases within native environments is currently lacking behind. Here we introduce a simple method to profile protease activity based on isolation of protease products from native lysates using a 96FASP filter, their analysis in a mass spectrometer and a custom data analysis pipeline. The method is significantly faster, cheaper, technically less demanding, easy to multiplex and produces accurate protease fingerprints. Using the blood cascade proteases as a case study, we obtain protease substrate profiles that can be used to map specificity, cleavage entropy and allosteric effects and to design protease probes. The data further show that protease substrate predictions enable the selection of potential physiological substrates for targeted validation in biochemical assays.

Indexed as

EntropyHigh-Throughput Screening AssaysAllosteric RegulationAmino Acid SequenceBlood CoagulationFluorescenceHEK293 CellsHumansMatrix MetalloproteinasesPeptide HydrolasesPeptidesSubstrate SpecificityThromboplastinMatrix MetalloproteinasesPeptide HydrolasesPeptidesThromboplastin

Identifiers

PMID33727531
PMCPMC7966775
OpenAlexW3138269968

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.