N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping

Sun, Shisheng; Hu, Yingwei; Ao, Minghui; Shah, Punit; Chen, Jing; Yang, Weiming; Jia, Xin; Tian, Yuan; Thomas, Stefani N.; Zhang, Hui

doi:10.1186/s12014-019-9254-0

Cited by 75 publications

(58 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the various types of glycosylation, N-glycosylation is most ubiquitous in eukaryotes. Over 7000 human proteins are N-glycosylated [2], and N-glycans with huge structural diversity regulate the various functions of proteins such as folding, trafficking, interactions with other proteins, and enzyme activity [3]. N-glycans (Glc 3 Man 9 GlcNAc 2 ) are covalently attached onto the asparagine residue of the consensus sequence (N-X-S/T, X P) of nascent glycoproteins by oligosaccharyltransferase (OST) complex in the endoplasmic reticulum (ER).…”

Section: Introductionmentioning

confidence: 99%

3D Structure and Function of Glycosyltransferases Involved in N-glycan Maturation

Nagae

Yamaguchi

Taniguchi

et al. 2020

IJMS

View full text Add to dashboard Cite

Glycosylation is the most ubiquitous post-translational modification in eukaryotes. N-glycan is attached to nascent glycoproteins and is processed and matured by various glycosidases and glycosyltransferases during protein transport. Genetic and biochemical studies have demonstrated that alternations of the N-glycan structure play crucial roles in various physiological and pathological events including progression of cancer, diabetes, and Alzheimer’s disease. In particular, the formation of N-glycan branches regulates the functions of target glycoprotein, which are catalyzed by specific N-acetylglucosaminyltransferases (GnTs) such as GnT-III, GnT-IVs, GnT-V, and GnT-IX, and a fucosyltransferase, FUT8s. Although the 3D structures of all enzymes have not been solved to date, recent progress in structural analysis of these glycosyltransferases has provided insights into substrate recognition and catalytic reaction mechanisms. In this review, we discuss the biological significance and structure-function relationships of these enzymes.

show abstract

Section: Introductionmentioning

confidence: 99%

3D Structure and Function of Glycosyltransferases Involved in N-glycan Maturation

Nagae

Yamaguchi

Taniguchi

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…To determine the structure of a glycan, identification and quantification of monosaccharides, as well as identification of glycosidic bonds between monosaccharides, are both required. Useful information can be obtained by comparing the chromatography and mass spectra of unidentified glycans and known structures, which will accelerate the analysis [ 21 , 22 , 23 , 24 ]. For this purpose, storage and management of glycan structure data are very important.…”

Section: Glycan Structure Databasesmentioning

confidence: 99%

“…Recently, a larger database called N -GlycositeAtlas ( ) containing more than 30,000 glycosite-containing peptides with >14,000 N -glycosylation sites from over 7200 N -glycoproteins was developed by the same lab [ 22 ]. These human glycosite-containing peptides were collected from over 100 publications and unpublished datasets, and then mapped to UniProt database.…”

Section: Glycoprotein Databasesmentioning

confidence: 99%

Databases and Bioinformatic Tools for Glycobiology and Glycoproteomics

Hong

et al. 2020

IJMS

View full text Add to dashboard Cite

Glycosylation plays critical roles in various biological processes and is closely related to diseases. Deciphering the glycocode in diverse cells and tissues offers opportunities to develop new disease biomarkers and more effective recombinant therapeutics. In the past few decades, with the development of glycobiology, glycomics, and glycoproteomics technologies, a large amount of glycoscience data has been generated. Subsequently, a number of glycobiology databases covering glycan structure, the glycosylation sites, the protein scaffolds, and related glycogenes have been developed to store, analyze, and integrate these data. However, these databases and tools are not well known or widely used by the public, including clinicians and other researchers who are not in the field of glycobiology, but are interested in glycoproteins. In this study, the representative databases of glycan structure, glycoprotein, glycan–protein interactions, glycogenes, and the newly developed bioinformatic tools and integrated portal for glycoproteomics are reviewed. We hope this overview could assist readers in searching for information on glycoproteins of interest, and promote further clinical application of glycobiology.

show abstract

“…To facilitate identification of intact N-linked glycopeptides from resulting 'oxo-spectra', the global and IMAC-based phosphopeptide-enriched phosphoproteomics data sets of the breast cancer xenograft tissues were searched using GPQuest against a human database containing over 30,000 known N-linked glycopeptide sequences and 181 N-linked glycan compositions 35 . The search results are summarized in Table 1.…”

Section: Identification Of N-linked Glycopeptides Of the Breast Tumormentioning

confidence: 99%

Reanalysis of global proteomic and phosphoproteomic data identified a large number of glycopeptides

Shah

Clark

et al. 2017

Preprint

Self Cite

View full text Add to dashboard Cite

Protein glycosylation plays fundamental roles in many cellular processes, and previous reports have shown dysregulation to be associated with several human diseases, including diabetes, cancer, and neurodegenerative disorders. Despite the vital role of glycosylation for proper protein function, the analysis of glycoproteins has been lagged behind to other protein modifications. In this study, we describe the re-analysis of global proteomic data from breast cancer xenograft tissues using recently developed software package GPQuest 2.0, revealing a large number of previously unidentified N-linked glycopeptides. More importantly, we found that using immobilized metal affinity chromatography (IMAC) technology for the enrichment of phosphopeptides had coenriched a substantial number of sialoglycopeptides, allowing for a large-scale analysis of sialoglycopeptides in conjunction with the analysis of phosphopeptides. Collectively, combined MS/MS analyses of global proteomic and phosphoproteomic datasets resulted in the identification of 6,724 N-linked glycopeptides from 617 glycoproteins derived from two breast cancer xenograft tissues. Next, we utilized GPQuest for the re-analysis of global and phosphoproteomic data generated from 108 human breast cancer tissues that were previously analyzed by Clinical Proteomic Analysis Consortium (CPTAC). Reanalysis of the CPTAC dataset resulted in the identification of 2,683 glycopeptides from the global proteomic data set and 4,554 glycopeptides from phosphoproteomic data set, respectively. Together, 11,292 N-linked glycopeptides corresponding to 1,731 N-linked glycosites from 883 human glycoproteins were identified from the two data sets. This analysis revealed an extensive number of glycopeptides hidden in the global and enriched in IMAC-based phosphopeptide-enriched proteomic data, information which would have remained unknown from the original study otherwise. The reanalysis described herein can be readily applied to identify glycopeptides from already existing data sets, providing insight into many important facets of protein glycosylation in different biological, physiological, and pathological processes.would not contain the sialic residue. Further investigation of the influence of IMAC-enrichment on intact glycopeptides, specifically sialylated intact glycopeptides is warranted, as well as the scheme of the co-enrichment of both phosphopeptides and intact glycopeptides. ConclusionsWith the rapid development of mass spectrometry and computational glycoproteomics tools, we can conduct a large-scale analysis of glycoproteome without specific glycopeptide enrichment and mass spectrometry analysis. In this study, we used our recently developed and improved intact glycopeptide analysis tool, GPQuest 2.0, to investigate the glycopeptide expression in two large datasets: two breast cancer xenograft samples and 108 CPTAC breast cancer tissues. The search results of 'oxo-spectra' and intact N-linked glycopeptides analysis demonstrated the feasibility of profiling glycoproteome utiliz...

show abstract

N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping

Cited by 75 publications

References 105 publications

3D Structure and Function of Glycosyltransferases Involved in N-glycan Maturation

3D Structure and Function of Glycosyltransferases Involved in N-glycan Maturation

Databases and Bioinformatic Tools for Glycobiology and Glycoproteomics

Reanalysis of global proteomic and phosphoproteomic data identified a large number of glycopeptides

Contact Info

Product

Resources

About