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Cited by 8Protease and Inhibitor MechanismsGenomics and Phylogenetic StudiesChromosomal and Genetic Variations

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Origin and Early Diversification of the Papain Family of Cysteine Peptidases

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Kordiš, Dušan, Turk, Vito·2023·International Journal of Molecular Sciences
DOI 10.3390/ijms241411761PMC PMC10380794

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Abstract

Peptidases of the papain family play a key role in protein degradation, regulated proteolysis, and the host–pathogen arms race. Although the papain family has been the subject of many studies, knowledge about its diversity, origin, and evolution in Eukaryota, Bacteria, and Archaea is limited; thus, we aimed to address these long-standing knowledge gaps. We traced the origin and expansion of the papain family with a phylogenomic analysis, using sequence data from numerous prokaryotic and eukaryotic proteomes, transcriptomes, and genomes. We identified the full complement of the papain family in all prokaryotic and eukaryotic lineages. Analysis of the papain family provided strong evidence for its early diversification in the ancestor of eukaryotes. We found that the papain family has undergone complex and dynamic evolution through numerous gene duplications, which produced eight eukaryotic ancestral paralogous C1A lineages during eukaryogenesis. Different evolutionary forces operated on C1A peptidases, including gene duplication, horizontal gene transfer, and gene loss. This study challenges the current understanding of the origin and evolution of the papain family and provides valuable insights into their early diversification. The findings of this comprehensive study provide guidelines for future structural and functional studies of the papain family.

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Metadata

Authors
Kordiš, D., & Turk, V.
Affiliations
  • Jožef Stefan Institute (SI)
  • Department of Biochemistry, Molecular and Structural Biology, J. Stefan Institute, 1000 Ljubljana, Slovenia
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-07-21
Volume
24
Issue
14
Pages
11761
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms241411761
PMC
PMC10380794
OpenAlex
W4385172689
Cited by
8
References
3
Citations by year
2025: 2 · 2024: 3 · 2023: 3
FWCI
1.01
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Preprints.org (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Slovenian Research Agency (P1-0207, P1-0140, J1-2473)
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Keywords
papain family, cysteine peptidases, protein evolution, eukaryotic origin, gene duplication, horizontal gene transfer, gene loss, host-pathogen arms race, protein degradation
MeSH terms
Archaea, Cysteine, Papain, Peptide Hydrolases, Phylogeny, Evolution, Molecular, Eukaryota, Cysteine Proteases

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