Proteoform: a single term describing protein complexity
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Measuring proteoforms can fill these gaps by capturing the full molecular composition of proteins and refining phenotypic correlations.
“Measurement of proteoforms (8) can close these gaps by capturing the complete molecular composition of proteins, refining phenotypic correlations.”
From The Blood Proteoform Atlas: A reference map of proteoforms in human hematopoietic cells (2022) · cites this paper as [8]
Mutations, alternative splicing, and PTMs generate many proteoforms from a single gene, greatly diversifying the proteome.
“Mutations, alternative splicing events, and post-translational modifications (PTMs) result in a host of proteoforms (a term referring to all the protein products that arise from a single gene) that greatly diversify the proteome [1–4].”
From Top-down proteomics: challenges, innovations, and applications in basic and clinical research (2020) · cites this paper as [3]
Top-down analysis can provide unique structural insights into proteins through precise molecular weight measurements, identification of multiple PTMs, and in-depth proteoform characterization.
“Top-down analysis can provide unique insights into a protein’s structure by providing precise molecular weight measurements, the identification of multiple PTMs5,16,28 and in-depth proteoform characterization (different forms of a single protein generated from a gene)32.”
From Recent trends of capillary electrophoresis‐mass spectrometry in proteomics research (2019) · cites this paper as [32]
Top-down mass spectrometry (MS)-based proteomics provides a comprehensive analysis of proteoforms to achieve a proteome-wide understanding of protein functions.
“Top-down mass spectrometry (MS)-based proteomics provides a comprehensive analysis of proteoforms to achieve a proteome-wide understanding of protein functions.”
From Nanoproteomics enables proteoform-resolved analysis of low-abundance proteins in human serum (2020) · cites this paper as [1]
The Human Proteoform Project is modeled roughly after the successful roadmap provided by the Human Genome Project, which generated the human reference genome sequence while advancing technology in the process.
“The project is modeled roughly after the successful roadmap provided by the HGP, which generated the human reference genome sequence while advancing technology in the process ( 2 , 3 , 5 ).”
From The Human Proteoform Project: Defining the human proteome (2021) · cites this paper as [3]
Genetic variation, alternative splicing, and posttranslational modification work together to create a rich variety of different proteoforms arising from human genes.
“Genetic variation, alternative splicing, and posttranslational modification (PTM) work together to create a rich variety of different proteoforms arising from our genes ( Fig. 1 ) ( 3 ).”
From The Human Proteoform Project: Defining the human proteome (2021) · cites this paper as [3]
Proteins are the central intermediaries between genotype and phenotype.
“Proteins are the central intermediaries between genotype and phenotype ( 2 – 4 ).”
From The Human Proteoform Project: Defining the human proteome (2021) · cites this paper as [3]
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“Protein post-translational modifications (PTMs) can alter the above properties, leading to diverse functions (Smith and Kelleher, 2018; Smith et al., 2013).”
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Self-citationThe Plant PTM Viewer, a central resource for exploring plant protein modifications.
Willems, P., Horne, A., van Parys, T., Goormachtig, S., Smet, I. D., Botzki, A., Breusegem, F. V., & Gevaert, K. (2019) · The Plant Journal · doi:10.1111/tpj.14345 · Cited by 98 · see citing works
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“, charge isoforms, molecules with a variety of post-translational modifications (PTMs), sequence variants, products resulting from truncation of protein, or alternative mRNA splicing [11, 12].”
Optimizing capillary electrophoresis for top‐down proteomics of 30–80 kDa proteins
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Self-citationA current perspective on snake venom composition and constituent protein families
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“Toxic proteins produced by different genes are classified as different toxins, whilst toxins with different sequences that are produced by the same gene are called proteoforms (Smith and Kelleher 2013); these can be the result of alternative splicing or post-translational modifications (Ogawa et al.”
BackgroundCleland, T. P., DeHart, C. J., Fellers, R. T., VanNispen, A. J., Greer, J. B., LeDuc, R. D., Parker, W. R., Thomas, P. M., Kelleher, N. L., & Brodbelt, J. S. (2017) · Journal of Proteome Research · doi:10.1021/acs.jproteome.7b00043 · Cited by 96 · see citing works
Self-citationPersonalized Drug Therapy: Innovative Concept Guided With Proteoformics
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“Theterm “ proteoform ” has been used for 11 years since 2012 (17, 25), leading to the research fi eld of proteoformics that focuses on theories and methods to study the morphological diversity of the proteome (22, 26).”
BackgroundMethodProton Transfer Charge Reduction Enables High-Throughput Top-Down Analysis of Large Proteoforms
Huguet, R., Mullen, C., Srzentić, K., Greer, J. B., Fellers, R. T., Zabrouskov, V., Syka, J. E. P., Kelleher, N. L., & Fornelli, L. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b03925 · Cited by 94 · see citing works
Self-citationTop-Down Proteomics and the Challenges of True Proteoform Characterization
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Analytical techniques for multiplex analysis of protein biomarkers
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“produced from a single gene product [115].”
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“As a result, a single gene encodes a set of distinct protein molecules, known as proteoforms [57].”
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Self-citationA Practical Guide to Small Protein Discovery and Characterization Using Mass Spectrometry
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Self-citationSystematic detection of functional proteoform groups from bottom-up proteomic datasets
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Proteomics Standards Initiative: Fifteen Years of Progress and Future Work
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Proteomes Are of Proteoforms: Embracing the Complexity
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A comprehensive pipeline for translational top-down proteomics from a single blood draw
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“This allows the identification of distinct intact covalent protein products – knownas ʻ proteoforms’–eachhavingasignaturemolecularweight [98] (Figure 2E).”
BackgroundAn atlas of protein turnover rates in mouse tissues
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Advances in mass spectrometry‐based glycomics
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Instrumentation at the leading edge of proteomics
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- Authors
- The Consortium for Top Down Proteomics, Smith, L. M., & Kelleher, N. L.
- Affiliations
- University of Wisconsin–Madison (US)
- Northwestern University (US)
- Corresponding author
- Kelleher, Neil L
- Venue
- Nature Methods
- Published
- 2013-02-27
- Volume
- 10
- Issue
- 3
- Pages
- 186-187
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- PMC
- PMC4114032
- OpenAlex
- W1568341953
- Cited by
- 1,528
- References
- 7
- Citations by year
- 2026: 102 · 2025: 115 · 2024: 139 · 2023: 141 · 2022: 124 · 2021: 146 · 2020: 145 · 2019: 113 · 2018: 106 · 2017: 105 · 2016: 95 · 2015: 94 · 2014: 66 · 2013: 29 · 2012: 2
- FWCI
- 42.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Funders
- National Institutes of Health (7p50hg004952-05)
- National Human Genome Research Institute (1P50 HG004952, P50 HG-004952)
- National Institute of General Medical Sciences (R01GM067193)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063491)
- National Institute of Neurological Disorders and Stroke (R01NS065263, P01NS049134)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- Keywords
- proteoforms, protein isoforms, post-translational modification, top-down proteomics, proteome sequencing
- MeSH terms
- Humans, Terminology as Topic, Protein Conformation, Genome, Human, Human Genome Project, Protein Isoforms, Databases, Genetic
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