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Current strategies and findings in clinically relevant post-translational modification-specific proteomics.

Pagel O, Loroch S, Sickmann A, Zahedi RP - Expert Rev Proteomics (2015)

Bottom Line: Thus, quantitative proteomics holds a great potential to discover, validate and accurately quantify biomarkers in body fluids and primary tissues.A major effort will be to improve the complete integration of robust but sensitive proteomics technology to clinical environments.Here, we discuss PTMs that are relevant for clinical research, with a focus on phosphorylation, glycosylation and proteolytic cleavage; furthermore, we give an overview on the current developments and novel findings in mass spectrometry-based PTM research.

View Article: PubMed Central - PubMed

Affiliation: Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Otto-Hahn-Straße 6b, 44227 Dortmund, Germany.

ABSTRACT
Mass spectrometry-based proteomics has considerably extended our knowledge about the occurrence and dynamics of protein post-translational modifications (PTMs). So far, quantitative proteomics has been mainly used to study PTM regulation in cell culture models, providing new insights into the role of aberrant PTM patterns in human disease. However, continuous technological and methodical developments have paved the way for an increasing number of PTM-specific proteomic studies using clinical samples, often limited in sample amount. Thus, quantitative proteomics holds a great potential to discover, validate and accurately quantify biomarkers in body fluids and primary tissues. A major effort will be to improve the complete integration of robust but sensitive proteomics technology to clinical environments. Here, we discuss PTMs that are relevant for clinical research, with a focus on phosphorylation, glycosylation and proteolytic cleavage; furthermore, we give an overview on the current developments and novel findings in mass spectrometry-based PTM research.

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Frequency of human PTMs. Summary of human PTMs which, according to UniProt and PhosphoSitePlus, have been detected (A) frequently, (B) less frequently and (C) rarely. For UniProt, the percentage of entries with experimental evidence is given (ECO:0000269). (D) The high number of known PTMs is in stark contrast to the limited knowledge about their involvement in disease.PTM: Post-translational modification.
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Figure 0002: Frequency of human PTMs. Summary of human PTMs which, according to UniProt and PhosphoSitePlus, have been detected (A) frequently, (B) less frequently and (C) rarely. For UniProt, the percentage of entries with experimental evidence is given (ECO:0000269). (D) The high number of known PTMs is in stark contrast to the limited knowledge about their involvement in disease.PTM: Post-translational modification.

Mentions: Currently, 469 PTMs are reported in the UniProt database (January 2015), of which 326 are reported in eukaryotes, 250 in bacteria, and 80 in archeae [1]. Some PTMs have only been found in specialized bacteria [2,3], but more than 100 different PTMs are reported in Homo sapiens. According to PhosphoSitePlus [4], protein phosphorylation is by far the most common PTM and has been detected on approximately 17,500 human gene products (Figure 2). Other frequently reported PTMs are ubiquitination (∼8100 proteins), lysine acetylation (∼6700 proteins), and lysine methylation (∼2400 proteins). The heterogeneous group of protein glycosylation has been reported for approximately 4500 proteins (PhosphoSitePlus and UniProt), but is estimated to occur on ≥50% of all human proteins [5]. Further PTMs such as succinylation, SUMOylation and citrullination [6,7] are increasingly added to the databases (Figure 2B). Importantly, >95% of these data are derived from mass spectrometry (MS)-based proteome studies [8], and with the advent of tools that allow automated re-processing of large-scale MS data sets [9] from repositories such as PRIDE [10] or proteomeXchange [11], it can be assumed that our knowledge about the prevalence of PTMs will further increase [12].


Current strategies and findings in clinically relevant post-translational modification-specific proteomics.

Pagel O, Loroch S, Sickmann A, Zahedi RP - Expert Rev Proteomics (2015)

Frequency of human PTMs. Summary of human PTMs which, according to UniProt and PhosphoSitePlus, have been detected (A) frequently, (B) less frequently and (C) rarely. For UniProt, the percentage of entries with experimental evidence is given (ECO:0000269). (D) The high number of known PTMs is in stark contrast to the limited knowledge about their involvement in disease.PTM: Post-translational modification.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4487610&req=5

Figure 0002: Frequency of human PTMs. Summary of human PTMs which, according to UniProt and PhosphoSitePlus, have been detected (A) frequently, (B) less frequently and (C) rarely. For UniProt, the percentage of entries with experimental evidence is given (ECO:0000269). (D) The high number of known PTMs is in stark contrast to the limited knowledge about their involvement in disease.PTM: Post-translational modification.
Mentions: Currently, 469 PTMs are reported in the UniProt database (January 2015), of which 326 are reported in eukaryotes, 250 in bacteria, and 80 in archeae [1]. Some PTMs have only been found in specialized bacteria [2,3], but more than 100 different PTMs are reported in Homo sapiens. According to PhosphoSitePlus [4], protein phosphorylation is by far the most common PTM and has been detected on approximately 17,500 human gene products (Figure 2). Other frequently reported PTMs are ubiquitination (∼8100 proteins), lysine acetylation (∼6700 proteins), and lysine methylation (∼2400 proteins). The heterogeneous group of protein glycosylation has been reported for approximately 4500 proteins (PhosphoSitePlus and UniProt), but is estimated to occur on ≥50% of all human proteins [5]. Further PTMs such as succinylation, SUMOylation and citrullination [6,7] are increasingly added to the databases (Figure 2B). Importantly, >95% of these data are derived from mass spectrometry (MS)-based proteome studies [8], and with the advent of tools that allow automated re-processing of large-scale MS data sets [9] from repositories such as PRIDE [10] or proteomeXchange [11], it can be assumed that our knowledge about the prevalence of PTMs will further increase [12].

Bottom Line: Thus, quantitative proteomics holds a great potential to discover, validate and accurately quantify biomarkers in body fluids and primary tissues.A major effort will be to improve the complete integration of robust but sensitive proteomics technology to clinical environments.Here, we discuss PTMs that are relevant for clinical research, with a focus on phosphorylation, glycosylation and proteolytic cleavage; furthermore, we give an overview on the current developments and novel findings in mass spectrometry-based PTM research.

View Article: PubMed Central - PubMed

Affiliation: Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Otto-Hahn-Straße 6b, 44227 Dortmund, Germany.

ABSTRACT
Mass spectrometry-based proteomics has considerably extended our knowledge about the occurrence and dynamics of protein post-translational modifications (PTMs). So far, quantitative proteomics has been mainly used to study PTM regulation in cell culture models, providing new insights into the role of aberrant PTM patterns in human disease. However, continuous technological and methodical developments have paved the way for an increasing number of PTM-specific proteomic studies using clinical samples, often limited in sample amount. Thus, quantitative proteomics holds a great potential to discover, validate and accurately quantify biomarkers in body fluids and primary tissues. A major effort will be to improve the complete integration of robust but sensitive proteomics technology to clinical environments. Here, we discuss PTMs that are relevant for clinical research, with a focus on phosphorylation, glycosylation and proteolytic cleavage; furthermore, we give an overview on the current developments and novel findings in mass spectrometry-based PTM research.

Show MeSH