hu.MAP3.0: atlas of human protein complexes by integration of >25,000 proteomic experiments
Macromolecular protein complexes carry out most cellular functions. Unfortunately, we lack the subunit composition for many human protein complexes. To address this gap we integrated >25,000 mass spectrometry experiments using a machine learning approach to identify >15,000 human protein complexes. We show our map of protein complexes is highly accurate and more comprehensive than previous maps, placing nearly 70% of human proteins into their physical contexts. We globally characterize our complexes using mass spectrometry based protein covariation data (ProteomeHD.2) and identify covarying complexes suggesting common functional associations. hu.MAP3.0 generates testable functional hypotheses for 472 uncharacterized proteins which we support using AlphaFold modeling. Additionally, we use AlphaFold modeling to identify 5871 mutually exclusive proteins in hu.MAP3.0 complexes suggesting complexes serve different functional roles depending on their subunit composition. We identify expression as the primary way cells and organisms relieve the conflict of mutually exclusive subunits. Finally, we import our complexes to EMBL-EBI's Complex Portal ( https://www.ebi.ac.uk/complexportal/home ) and provide complexes through our hu.MAP3.0 web interface ( https://humap3.proteincomplexes.org/ ). We expect our resource to be highly impactful to the broader research community.
Authors
- Savvas Kourtis (ORCID: https://orcid.org/0000-0002-3800-0853)
- Sandra Orchard (ORCID: https://orcid.org/0000-0002-8878-3972)
- Kevin Drew (ORCID: https://orcid.org/0000-0002-1260-4413)
- Sara Sdelci (ORCID: https://orcid.org/0000-0003-1330-4364)
- Henning Hermjakob (ORCID: https://orcid.org/0000-0001-8479-0262)
- Georg Kustatscher (ORCID: https://orcid.org/0000-0001-8955-0866)
- Erin R Claussen
- Samantha N Fischer
Institutions
- European Bioinformatics Institute (GB)
- University of Illinois Chicago (US)
- Wellcome Centre for Cell Biology (GB)
- Centre for Genomic Regulation (ES)
- University of Edinburgh (GB)
Publication Details
- Journal
- Molecular Systems Biology
- Published
- 2025-05-27
- DOI
- https://doi.org/10.1038/s44320-025-00121-5
- Citations
- 9
- Primary Topic
- Advanced Proteomics Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 6.81
Funders
- National Science Foundation
- European Bioinformatics Institute
- European Molecular Biology Laboratory
- Royal Society
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institutes of Health
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- National Institute on Aging
- National Heart, Lung, and Blood Institute
- National Human Genome Research Institute
- National Eye Institute
- National Cancer Institute
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development