ArticleThe Journal of biological chemistry2012
Site-specific O-glucosylation of the epidermal growth factor-like (EGF) repeats of notch: efficiency of glycosylation is affected by proper folding and amino acid sequence of individual EGF repeats.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 80 citations in OpenAlex.
- ER quality control of Crumbs2 and Notch proteins by GXYLT1-dependent xylosyl elongation of O-glucose glycans.The Journal of biological chemistry · 2026Article
- Protein β-O-glucosylation by Legionella LtpM through short consensus sequons G-T/S and S-G.Nature chemical biology · 2025Article
- Article
- Marfan syndrome variation of the POGLUT2 and POGLUT3 consensus sequence can produce aberrant fibrillin-1 O-glucosylation.The Journal of biological chemistry · 2025Article
- FUT10 and FUT11 are protein O-fucosyltransferases that modify protein EMI domains.Nature chemical biology · 2025Article
- Analysis of endogenous NOTCH1 from POFUT1 S162L patient fibroblasts reveals the importance of the O-fucose modification on EGF12 in human development.Glycobiology · 2024Article
- SLC35D3 promotes white adipose tissue browning to ameliorate obesity by NOTCH signaling.Nature communications · 2023Article
- Article
- Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing.Experimental & molecular medicine · 2023Article
- Significant Roles of NotchMolecules (Basel, Switzerland) · 2022Review
- Generation of Properly Folded Epidermal Growth Factor-Like (EGF) Repeats and Glycosyltransferases Enables In Vitro O-Glycosylation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Dissecting the role of EYS in retinal degeneration: clinical and molecular aspects and its implications for future therapy.Orphanet journal of rare diseases · 2021Review
- Coagulation factor IX analysis in bioreactor cell culture supernatant predicts quality of the purified product.Communications biology · 2021Article
- Current Views on the Roles ofBiomolecules · 2021Review
- Structure, function, and pathology of protein O-glucosyltransferases.Cell death & disease · 2021Review
- Multifaceted regulation of Notch signaling by glycosylation.Glycobiology · 2021Review
- Other Types of Glycosylation.Advances in experimental medicine and biology · 2021Article
- Meta-heterogeneity: Evaluating and Describing the Diversity in Glycosylation Between Sites on the Same Glycoprotein.Molecular & cellular proteomics : MCP · 2021Review
- Expression, purification, and glycosylation of epidermal growth factor-like repeat 27 from mouse NOTCH1.Protein expression and purification · 2020Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
O-Glucosylation of epidermal growth factor-like (EGF) repeats in the extracellular domain of Notch is essential for Notch function. O-Glucose can be elongated by xylose to the trisaccharide, Xylα1-3Xylα1-3Glcβ1-O-Ser, whose synthesis is catalyzed by the consecutive action of three glycosyltransferases. A UDP-glucose:protein O-glucosyltransferase (Poglut/Rumi) transfers O-glucose to serine within the O-glucose consensus. Subsequently, either of two UDP-xylose:glucoside xylosyltransferases (Gxylt1 or Gxylt2) transfers xylose to O-glucose. Finally, a UDP-xylose:xyloside xylosyltransferase (Xxylt1) transfers xylose to Xylα1-3Glcβ1-O-EGF. Our prior site-mapping studies demonstrated that O-glucose consensus sites are modified at high but variable stoichiometries in mouse Notch1 and identified a novel glycosylation site with alanine in place of proline, suggesting a revised, broader consensus sequence (CXSX(P/A)C). Here we examined the molecular basis for this site specificity. A panel of EGF repeats from human coagulation factor 9 (FA9), mouse Notch1, and Notch2 were bacterially expressed and purified by reverse phase HPLC for use in in vitro enzyme assays. We demonstrate that proper folding of EGF repeats is essential for glycosylation by Poglut/Rumi, that alanine can substitute for proline in the context of coagulation factor 9 EGF repeat for O-glucose transfer, confirming the new consensus sequence, and that positively charged residues within the O-glucose consensus sequence reduce efficiency of glycosylation by Poglut/Rumi. Moreover, proper folding of EGF repeats is also important for the activities of Gxylt1, Gxylt2, and Xxylt1. These results indicate that protein folding and amino acid sequences of individual EGF repeats fundamentally affect both attachment and elongation of O-glucose glycans.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.