ArticleJournal of proteome research2014
Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome.
Article in Journal of proteome research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 102 citations in OpenAlex.
- SIMPATICO-Streamlined Isolation of the N-Terminome via Phosphonate Tagging and Coordination-Based Depletion.Molecular & cellular proteomics : MCP · 2026Article
- N-terminomics and proteomics analysis of Calpain-2 reveal key proteolytic processing of metabolic and cell adhesion proteins.Protein science : a publication of the Protein Society · 2025Article
- RBC-GEM: A genome-scale metabolic model for systems biology of the human red blood cell.PLoS computational biology · 2025Article
- Red Blood Cell Omics and Machine Learning in Transfusion Medicine: Singularity Is Near.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2023Review
- Sphingosine 1-phosphate has a negative effect on RBC storage quality.Blood advances · 2023Article
- Extended N-Terminal Acetyltransferase Naa50 in Filamentous Fungi Adds to Naa50 Diversity.International journal of molecular sciences · 2022Article
- Mechanistic convergence across initiation sites for RAN translation in fragile X associated tremor ataxia syndrome.Human molecular genetics · 2022Article
- The protein organization of a red blood cell.Cell reports · 2022Article
- HUNTER: Sensitive Automated Characterization of Proteolytic Systems by N Termini Enrichment from Microscale Specimen.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Sensitive Plant N-Terminome Profiling with HUNTER.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The interactome of the N-terminus of band 3 regulates red blood cell metabolism and storage quality.Haematologica · 2021Article
- Combinatorial analysis of translation dynamics reveals eIF2 dependence of translation initiation at near-cognate codons.Nucleic acids research · 2021Article
- Insight into the human pathodegradome of the V8 protease from Staphylococcus aureus.Cell reports · 2021Article
- MANTI: Automated Annotation of Protein N-Termini for Rapid Interpretation of N-Terminome Data Sets.Analytical chemistry · 2021Article
- Impact of WIN site inhibitor on the WDR5 interactome.Cell reports · 2021Article
- Post-translational Modifications of the Protein Termini.Frontiers in cell and developmental biology · 2021Review
- ExteNDing Proteome Coverage with Legumain as a Highly Specific Digestion Protease.Analytical chemistry · 2020Article
- Sensitive Determination of Proteolytic Proteoforms in Limited Microscale Proteome Samples.Molecular & cellular proteomics : MCP · 2019Article
- Internalization of Erythrocyte Acylpeptide Hydrolase Is Required for Asexual Replication of Plasmodium falciparum.mSphere · 2019Article
- Quantitative comparative analysis of human erythrocyte surface proteins between individuals from two genetically distinct populations.Communications biology · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
A goal of the Chromosome-centric Human Proteome Project is to identify all human protein species. With 3844 proteins annotated as "missing", this is challenging. Moreover, proteolytic processing generates new protein species with characteristic neo-N termini that are frequently accompanied by altered half-lives, function, interactions, and location. Enucleated and largely void of internal membranes and organelles, erythrocytes are simple yet proteomically challenging cells due to the high hemoglobin content and wide dynamic range of protein concentrations that impedes protein identification. Using the N-terminomics procedure TAILS, we identified 1369 human erythrocyte natural and neo-N-termini and 1234 proteins. Multiple semitryptic N-terminal peptides exhibited improved mass spectrometric identification properties versus the intact tryptic peptide enabling identification of 281 novel erythrocyte proteins and six missing proteins identified for the first time in the human proteome. With an improved bioinformatics workflow, we developed a new classification system and the Terminus Cluster Score. Thereby we described a new stabilizing N-end rule for processed protein termini, which discriminates novel protein species from degradation remnants, and identified protein domain hot spots susceptible to cleavage. Strikingly, 68% of the N-termini were within genome-encoded protein sequences, revealing alternative translation initiation sites, pervasive endoproteolytic processing, and stabilization of protein fragments in vivo. The mass spectrometry proteomics data have been deposited to ProteomeXchange with the data set identifier <PXD000434>.
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