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<p>Small open reading frames (sORFs) and their encoded microproteins are increasingly recognized as a widespread but poorly characterized components of the human proteome. Here we show a Human Microprotein Atlas (HMPA) platform that integrates 617,462 human microproteins with sequence features, predicted three-dimensional structures, variant effect predictions, subcellular localization, essentiality, and bioactivity annotations. Structural analyses revealed substantial conformational diversity, and structure-based functional inference suggested roles in cellular regulation, signaling, and cell-cell communication. Deep learning-based analyses further prioritized microproteins with tissue-specific essentiality and enabled the prediction of diverse bioactivities across multiple functional categories. To support the&#xa0;exploration of these data, we also provide an interactive web server with sequence-, structure-, and function-oriented search and analysis utilities. This resource provides a systematic framework for studying microprotein biology and supports the discovery of functional and therapeutically relevant microproteins.</p>

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Comprehensive annotation and analysis of human microproteins by human microprotein atlas platform

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月12日

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  • Boming Kang,
  • Rui Fan,
  • Xiangwen Ji,
  • Yuan Zhou,
  • Qinghua Cui,
  • Chunmei Cui

摘要

Small open reading frames (sORFs) and their encoded microproteins are increasingly recognized as a widespread but poorly characterized components of the human proteome. Here we show a Human Microprotein Atlas (HMPA) platform that integrates 617,462 human microproteins with sequence features, predicted three-dimensional structures, variant effect predictions, subcellular localization, essentiality, and bioactivity annotations. Structural analyses revealed substantial conformational diversity, and structure-based functional inference suggested roles in cellular regulation, signaling, and cell-cell communication. Deep learning-based analyses further prioritized microproteins with tissue-specific essentiality and enabled the prediction of diverse bioactivities across multiple functional categories. To support the exploration of these data, we also provide an interactive web server with sequence-, structure-, and function-oriented search and analysis utilities. This resource provides a systematic framework for studying microprotein biology and supports the discovery of functional and therapeutically relevant microproteins.