{
  "abstract": "Lysine deserts-extended, continuous protein regions containing no lysine residues-occur across diverse proteomes, yet their definition, evolutionary origins and biological significance remain incompletely understood. In this Review, I examine the evidence linking local lysine depletion to protein regulation, with particular emphasis on ubiquitin- and proteasome-dependent pathways. Studies of toxin catalytic subunits and endogenous components of the ubiquitin-proteasome system show that introducing lysines at selected positions can alter ubiquitylation, protein turnover or function. These findings support a context-dependent model in which lysine deserts can limit the availability of ubiquitin acceptor sites within particular structural and enzymatic environments, rather than generally protecting entire proteins from modification or degradation. I discuss how lysine position, solvent accessibility, E3 ligase geometry and protein conformation determine the consequences of lysine introduction, and how N-terminal or non-lysine ubiquitylation as well as ubiquitin-independent proteolysis can bypass lysine depletion. I also consider the reported enrichment of lysine deserts in selected Actinobacteria and Mycobacterium phages, highlighting a testable Pup-proteasome adaptation hypothesis. Finally, I discuss potential functions beyond ubiquitylation and the methodological challenges of distinguishing selected lysine depletion from compositional bias or chance.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Protein Metabolism, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Natalia A Szulc"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cq63cktje8sat.bib",
  "cited_by": 0,
  "doi": "10.3389/fmolb.2026.1959694",
  "fulltext_url": "https://europepmc.org/articles/PMC13696103",
  "id": "cq63cktje8sat",
  "issns": [
    "2296-889X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42928854",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Ubiquitin and proteasome pathways"
    ]
  ],
  "openalex": "W7221455812",
  "pdf_url": "https://europepmc.org/articles/PMC13696103?pdf=render",
  "pmcid": "PMC13696103",
  "pmid": "42928854",
  "published": "2026-10-12",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cq63cktje8sat.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928854",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928854"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Ubiquitin and proteasome pathways",
      "subfield": "molecular-biology"
    }
  ],
  "title": "When absence becomes functional: lysine deserts in protein regulation and evolution.",
  "title_text": "When absence becomes functional: lysine deserts in protein regulation and evolution.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:18Z",
  "url": "https://research.draconitic.com/paper/cq63cktje8sat",
  "venue": "Frontiers in molecular biosciences",
  "versions": []
}