ArticleProceedings of the National Academy of Sciences of the United States of America2023
Classification of domains in predicted structures of the human proteome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed.
- A histidine switch controls the pH-responsive self-assembly of a helical protein filament.bioRxiv : the preprint server for biology · 2026Article
- T3SS effector and regulator discovery by predicting interacting partners of T3SS chaperones in Pseudomonas aeruginosa.Protein science : a publication of the Protein Society · 2026Article
- ECOD: Classification of domains in AFDB Swiss-Prot structure predictions.PLoS computational biology · 2026Article
- From CASP13 to the Nobel Prize: DeepMind's AlphaFold Journey in Revolutionizing Protein Structure Prediction and Beyond.Current protein & peptide science · 2026Review
- C17orf75 (Njmu-R1) promotes hepatocellular carcinoma progression: a pan-cancer analysis and experimental validation.Frontiers in immunology · 2026Article
- Using evolutionary context to classify difficult protein folds.PLoS computational biology · 2025Article
- Exploring the Terra incognita of AI-based domain classifications.Protein science : a publication of the Protein Society · 2025Article
- CoDIAC: A comprehensive approach for interaction analysis provides insights into SH2 domain function and regulation.Science signaling · 2025Article
- Predicting protein-protein interactions in the human proteome.Science (New York, N.Y.) · 2025Article
- DrugDomain 2.0: comprehensive database of protein domains-ligands/drugs interactions across the whole Protein Data Bank.bioRxiv : the preprint server for biology · 2025Article
- Assessing Structural Classification Using AlphaFold2 Models Through ECOD-Based Comparative Analysis.Proteins · 2025Article
- CoDIAC: A comprehensive approach for interaction analysis reveals novel insights into SH2 domain function and regulation.bioRxiv : the preprint server for biology · 2025Article
- Uncovering the domain language of protein functionality and cell phenotypes using DANSy.bioRxiv : the preprint server for biology · 2025Article
- Recent progress and future challenges in structure-based protein-protein interaction prediction.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Refinement and curation of homologous groups facilitated by structure prediction.Protein science : a publication of the Protein Society · 2025Article
- A structural atlas of death domain fold proteins reveals their versatile roles in biology and function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lessons from Deep Learning Structural Prediction of Multistate Multidomain Proteins-The Case Study of Coiled-Coil NOD-like Receptors.International journal of molecular sciences · 2025Article
- DrugDomain 2.0: Comprehensive database of protein domains-ligands/drugs interactions across the whole Protein Data Bank.Computational and structural biotechnology journal · 2025Article
- DPAM-AI: a domain parser for AlphaFold models powered by artificial intelligence.Bioinformatics (Oxford, England) · 2024Article
- Bridging the Gap between Sequence and Structure Classifications of Proteins with AlphaFold Models.Journal of molecular biology · 2024Article
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6 authors.
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Abstract
Recent advances in protein structure prediction have generated accurate structures of previously uncharacterized human proteins. Identifying domains in these predicted structures and classifying them into an evolutionary hierarchy can reveal biological insights. Here, we describe the detection and classification of domains from the human proteome. Our classification indicates that only 62% of residues are located in globular domains. We further classify these globular domains and observe that the majority (65%) can be classified among known folds by sequence, with a smaller fraction (33%) requiring structural data to refine the domain boundaries and/or to support their homology. A relatively small number (966 domains) cannot be confidently assigned using our automatic pipelines, thus demanding manual inspection. We classify 47,576 domains, of which only 23% have been included in experimental structures. A portion (6.3%) of these classified globular domains lack sequence-based annotation in InterPro. A quarter (23%) have not been structurally modeled by homology, and they contain 2,540 known disease-causing single amino acid variations whose pathogenesis can now be inferred using AF models. A comparison of classified domains from a series of model organisms revealed expansions of several immune response-related domains in humans and a depletion of olfactory receptors. Finally, we use this classification to expand well-known protein families of biological significance. These classifications are presented on the ECOD website (http://prodata.swmed.edu/ecod/index_human.php).
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