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Xylosyltransferase II

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https://www.readbyqxmd.com/read/26027496/homozygosity-for-frameshift-mutations-in-xylt2-result-in-a-spondylo-ocular-syndrome-with-bone-fragility-cataracts-and-hearing-defects
#1
Craig F Munns, Somayyeh Fahiminiya, Nabin Poudel, Maria Cristina Munteanu, Jacek Majewski, David O Sillence, Jordan P Metcalf, Andrew Biggin, Francis Glorieux, François Fassier, Frank Rauch, Myron E Hinsdale
Heparan and chondroitin/dermatan sulfated proteoglycans have a wide range of roles in cellular and tissue homeostasis including growth factor function, morphogen gradient formation, and co-receptor activity. Proteoglycan assembly initiates with a xylose monosaccharide covalently attached by either xylosyltransferase I or II. Three individuals from two families were found that exhibited similar phenotypes. The index case subjects were two brothers, individuals 1 and 2, who presented with osteoporosis, cataracts, sensorineural hearing loss, and mild learning defects...
June 4, 2015: American Journal of Human Genetics
https://www.readbyqxmd.com/read/25940448/phenotype-based-clustering-of-glycosylation-related-genes-by-rnai-mediated-gene-silencing
#2
Miki Yamamoto-Hino, Hideki Yoshida, Tomomi Ichimiya, Sho Sakamura, Megumi Maeda, Yoshinobu Kimura, Norihiko Sasaki, Kiyoko F Aoki-Kinoshita, Akiko Kinoshita-Toyoda, Hidenao Toyoda, Ryu Ueda, Shoko Nishihara, Satoshi Goto
Glycan structures are synthesized by a series of reactions conducted by glycosylation-related (GR) proteins such as glycosyltransferases, glycan-modifying enzymes, and nucleotide-sugar transporters. For example, the common core region of glycosaminoglycans (GAGs) is sequentially synthesized by peptide-O-xylosyltransferase, β1,4-galactosyltransferase I, β1,3-galactosyltransferase II, and β1,3-glucuronyltransferase. This raises the possibility that functional impairment of GR proteins involved in synthesis of the same glycan might result in the same phenotypic abnormality...
June 2015: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/25748573/xylosyltransferase-ii-is-the-predominant-isoenzyme-which-is-responsible-for-the-steady-state-level-of-xylosyltransferase-activity-in-human-serum
#3
Joachim Kuhn, Christian Götting, Brendan J Beahm, Carolyn R Bertozzi, Isabel Faust, Patricia Kuzaj, Cornelius Knabbe, Doris Hendig
In mammals, two active xylosyltransferase isoenzymes (EC 2.4.2.16) exist. Both xylosyltransferases I and II (XT-I and XT-II) catalyze the transfer of xylose from UDP-xylose to select serine residues in the proteoglycan core protein. Altered XT activity in human serum was found to correlate directly with various diseases such as osteoarthritis, systemic sclerosis, liver fibrosis, and pseudoxanthoma elasticum. To interpret the significance of the enzyme activity alteration observed in disease states it is important to know which isoenzyme is responsible for the XT activity in serum...
April 10, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/25704086/identification-and-characterization-of-human-xylosyltransferase-ii-promoter-single-nucleotide-variants
#4
Isabel Faust, Kai Oliver Böker, Christina Eirich, Dagmar Akkermann, Joachim Kuhn, Cornelius Knabbe, Doris Hendig
The human isoenzymes xylosyltransferase-I and -II (XT-I, XT-II) catalyze the rate-limiting step in proteoglycan biosynthesis. Therefore, serum XT activity, mainly representing XT-II activity, displays a powerful biomarker to quantify the actual proteoglycan synthesis rate. Serum XT activity is increased up to 44% in disorders which are characterized by an altered proteoglycan metabolism, whereby underlying regulatory mechanisms remain unclear. The aim of this study was to investigate new regulatory pathways by identifying and characterizing naturally occurring XYLT2 promoter sequence variants as well as their potential influence on promoter activity and serum XT activity...
March 20, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/25024048/blood-cells-transcriptomics-as-source-of-potential-biomarkers-of-articular-health-improvement-effects-of-oral-intake-of-a-rooster-combs-extract-rich-in-hyaluronic-acid
#5
Juana Sánchez, M Luisa Bonet, Jaap Keijer, Evert M van Schothorst, Ingrid Mölller, Carles Chetrit, Daniel Martinez-Puig, Andreu Palou
The aim of the study was to explore peripheral blood gene expression as a source of biomarkers of joint health improvement related to glycosaminoglycan (GAG) intake in humans. Healthy individuals with joint discomfort were enrolled in a randomized, double-blind, placebo-controlled intervention study in humans. Subjects ate control yoghurt or yoghurt supplemented with a recently authorized novel food in Europe containing hyaluronic acid (65 %) from rooster comb (Mobilee™ as commercial name) for 90 days. Effects on functional quality-of-life parameters related to joint health were assessed...
September 2014: Genes & Nutrition
https://www.readbyqxmd.com/read/24666997/phylogenetic-analysis-of-pectin-related-gene-families-in-physcomitrella-patens-and-nine-other-plant-species-yields-evolutionary-insights-into-cell-walls
#6
Thomas W McCarthy, Joshua P Der, Loren A Honaas, Claude W dePamphilis, Charles T Anderson
BACKGROUND: Pectins are acidic sugar-containing polysaccharides that are universally conserved components of the primary cell walls of plants and modulate both tip and diffuse cell growth. However, many of their specific functions and the evolution of the genes responsible for producing and modifying them are incompletely understood. The moss Physcomitrella patens is emerging as a powerful model system for the study of plant cell walls. To identify deeply conserved pectin-related genes in Physcomitrella, we generated phylogenetic trees for 16 pectin-related gene families using sequences from ten plant genomes and analyzed the evolutionary relationships within these families...
March 26, 2014: BMC Plant Biology
https://www.readbyqxmd.com/read/23581628/discovery-and-investigation-of-o-xylosylation-in-engineered-proteins-containing-a-ggggs-n-linker
#7
Dingyi Wen, Susan F Foley, Xiaoping L Hronowski, Sheng Gu, Werner Meier
Protein engineering is a powerful tool for designing or modifying therapeutic proteins for enhanced efficacy, greater safety, reduced immunogenicity, and better delivery. GGGGS [(G4S)n] linkers are commonly used when engineering a protein, because of their flexibility and resistance to proteases. However, post-translational modifications (PTMs) can occur at the Ser residue in these linkers. Here, we report, for the first time, the occurrence of O-xylosylation at the serine residue in (G4S)n>2 linkers. The O-xylosylation was discovered as a result of molecular mass determination, peptide mapping analysis, and MS/MS sequencing...
May 7, 2013: Analytical Chemistry
https://www.readbyqxmd.com/read/23542338/a-genomewide-association-study-of-smoking-relapse-in-four-european-population-based-samples
#8
Federica Tozzi, Alexander Teumer, Marcus Munafò, Rajesh Rawal, Gbenga Kazeem, Marcel Gerbaulet, Wendy McArdle, Howard Chilcoat, Angela Döring, Norbert Dahmen, Vincent Mooser, Matthias Nauck, Susan M Ring, Justin P Rubio, Peter Vollenweider, Gérard Waeber, Ulrich John, Henry Völzke, Georg Homuth, Harald J Freyberger, Uwe Völker, George Davey-Smith, Christian Gieger, Martin Preisig, Hans J Grabe
OBJECTIVES: Genomewide association studies (GWAS) have identified clear evidence of genetic markers for nicotine dependence. Other smoking phenotypes have been tested, but the results are less consistent. The tendency to relapse versus the ability to maintain long-term abstinence has received little attention in genetic studies; thus, our aim was to provide a better biological understanding of this phenotype through the identification of genetic loci associated with smoking relapse. METHODS: We carried out a GWAS on data from two European population-based collections, including a total of 835 cases (relapsers) and 990 controls (abstainers)...
August 2013: Psychiatric Genetics
https://www.readbyqxmd.com/read/23400704/time-resolved-fluorescence-imaging-reveals-differential-interactions-of-n-glycan-processing-enzymes-across-the-golgi-stack-in-planta
#9
Jennifer Schoberer, Eva Liebminger, Stanley W Botchway, Richard Strasser, Chris Hawes
N-Glycan processing is one of the most important cellular protein modifications in plants and as such is essential for plant development and defense mechanisms. The accuracy of Golgi-located processing steps is governed by the strict intra-Golgi localization of sequentially acting glycosidases and glycosyltransferases. Their differential distribution goes hand in hand with the compartmentalization of the Golgi stack into cis-, medial-, and trans-cisternae, which separate early from late processing steps. The mechanisms that direct differential enzyme concentration are still unknown, but the formation of multienzyme complexes is considered a feasible Golgi protein localization strategy...
April 2013: Plant Physiology
https://www.readbyqxmd.com/read/22886070/first-identification-and-functional-analysis-of-the-human-xylosyltransferase-ii-promoter
#10
Benjamin Müller, Christian Prante, Cornelius Knabbe, Knut Kleesiek, Christian Götting
Recently, we demonstrated that the human xylosyltransferase II (XT-II) has enzymatic activity and is able to catalyze the initial and rate-limiting step in the biosynthesis of glycosaminoglycans (GAGs) like chondroitin and dermatan sulfate, as well as heparan sulfate and heparin. Therefore, this enzyme also very likely assumes a crucial regulatory role in the biosynthesis of proteoglycans (PGs). In this study, we identified and characterized for the first time the XYLT2 gene promoter region and transcription factors involved in its regulation...
April 2013: Glycoconjugate Journal
https://www.readbyqxmd.com/read/22455987/injectable-perlecan-domain-1-hyaluronan-microgels-potentiate-the-cartilage-repair-effect-of-bmp2-in-a-murine-model-of-early-osteoarthritis
#11
Padma P Srinivasan, Sarah Y McCoy, Amit K Jha, Weidong Yang, Xinqiao Jia, Mary C Farach-Carson, Catherine B Kirn-Safran
The goal of this study was to use bioengineered injectable microgels to enhance the action of bone morphogenetic protein 2 (BMP2) and stimulate cartilage matrix repair in a reversible animal model of osteoarthritis (OA). A module of perlecan (PlnD1) bearing heparan sulfate (HS) chains was covalently immobilized to hyaluronic acid (HA) microgels for the controlled release of BMP2 in vivo. Articular cartilage damage was induced in mice using a reversible model of experimental OA and was treated by intra-articular injection of PlnD1-HA particles with BMP2 bound to HS...
April 2012: Biomedical Materials
https://www.readbyqxmd.com/read/22117070/molecular-cloning-of-a-xylosyltransferase-that-transfers-the-second-xylose-to-o-glucosylated-epidermal-growth-factor-repeats-of-notch
#12
Maya K Sethi, Falk F R Buettner, Angel Ashikov, Vadim B Krylov, Hideyuki Takeuchi, Nikolay E Nifantiev, Robert S Haltiwanger, Rita Gerardy-Schahn, Hans Bakker
The extracellular domain of Notch contains epidermal growth factor (EGF) repeats that are extensively modified with different O-linked glycans. O-Fucosylation is essential for receptor function, and elongation with N-acetylglucosamine, catalyzed by members of the Fringe family, modulates Notch activity. Only recently, genes encoding enzymes involved in the O-glucosylation pathway have been cloned. In the Drosophila mutant rumi, characterized by a mutation in the protein O-glucosyltransferase, Notch signaling is impaired in a temperature-dependent manner, and a mouse knock-out leads to embryonic lethality...
January 20, 2012: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/22024534/arabidopsis-%C3%AE-1-2-xylosyltransferase-substrate-specificity-and-participation-in-the-plant-specific-n-glycosylation-pathway
#13
Hiroyuki Kajiura, Toru Okamoto, Ryo Misaki, Yoshiharu Matsuura, Kazuhito Fujiyama
β1,2-Xylosyltransferase (XYLT) is a plant-specific glycosyltransferase that contributes to the biosynthesis of N-glycoproteins in plants. However, the specificity of XYLT for N-glycans has not yet been completely clarified. To gain insights into the function of XYLT in the plant N-glycosylation pathway, we examined the acceptor substrate specificity of recombinant Arabidopsis XYLT (AtXYLT) using 2-aminopyridine-labeled N-glycans as the substrates and confirmed the N-glycans of Arabidopsis xylt mutant. Recombinant AtXYLT expressed in insect cells required the β1,2-linked N-acetylglucosamine (GlcNAc) residue at the nonreducing terminus of the α1,3-branched mannose (Man) residue (GlcNAcβ1,2-Manα1,3-Man; GNM3B) for activity...
January 2012: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/21421394/a-putative-arabidopsis-thaliana-glycosyltransferase-at4g01220-which-is-closely-related-to-three-plant-cell-wall-specific-xylosyltransferases-is-differentially-expressed-spatially-and-temporally
#14
Jonatan U Fangel, Bent L Petersen, Niels B Jensen, William G T Willats, Antony Bacic, Jack Egelund
Plant cell wall polysaccharides are amongst the most complex, heterogeneous and abundant bio-molecules on earth. This makes the biosynthetic enzymes, namely the glycosyltransferases and polysaccharide synthases, important research targets in plant science and biotechnology. As an initial step to characterize At4g01220, a putative Arabidopsis thaliana encoding glycosyltransferases in CAZy GT-family-77 that is similar to three known xylosyltransferases involved in the biosynthesis of the pectic polysaccharide, rhamnogalacturonan II, we conducted an expression analysis...
March 2011: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/21288267/male-gametophyte-defective-4-encodes-a-rhamnogalacturonan-ii-xylosyltransferase-and-is-important-for-growth-of-pollen-tubes-and-roots-in-arabidopsis
#15
Xiao-Lei Liu, Lifeng Liu, Qian-Kun Niu, Chuan Xia, Ke-Zhen Yang, Rui Li, Li-Qun Chen, Xue-Qin Zhang, Yihua Zhou, De Ye
In flowering plants, the growth of pollen tubes is essential for the delivery of sperm to the egg cells. Although many factors (including cell-wall properties) are involved in this process, little is known about the underlying molecular mechanisms that regulate the growth of pollen tubes. We report here the characterization of an Arabidopsis mutant male gametophyte defective 4 (mgp4) that is severely defective in pollen tube growth. The mgp4 mutation also impairs root growth of pollen-rescued mgp4 mutant plants generated by expressing MGP4 cDNA under the control of a pollen grain/tube-specific promoter...
February 2011: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/21143678/subcompartment-localization-of-the-side-chain-xyloglucan-synthesizing-enzymes-within-golgi-stacks-of-tobacco-suspension-cultured-cells
#16
Laurence Chevalier, Sophie Bernard, Yasmina Ramdani, Romain Lamour, Muriel Bardor, Patrice Lerouge, Marie-Laure Follet-Gueye, Azeddine Driouich
Xyloglucan is the dominant hemicellulosic polysaccharide of the primary cell wall of dicotyledonous plants that plays a key role in plant development. It is well established that xyloglucan is assembled within Golgi stacks and transported in Golgi-derived vesicles to the cell wall. It is also known that the biosynthesis of xyloglucan requires the action of glycosyltransferases including α-1,6-xylosyltransferase, β-1,2-galactosyltransferase and α-1,2-fucosyltransferase activities responsible for the addition of xylose, galactose and fucose residues to the side chains...
December 2010: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/19944077/differences-in-gene-expression-of-human-xylosyltransferases-and-determination-of-acceptor-specificities-for-various-proteoglycans
#17
COMPARATIVE STUDY
Christina Roch, Joachim Kuhn, Knut Kleesiek, Christian Götting
The xylosyltransferase (XT) isoforms XT-I and XT-II initiate the posttranslational glycosaminoglycan (GAG) synthesis. Here, we determined the relative expression of both isoforms in 33 human cell lines. The majority of tested cell lines showed dominant XYLT2 gene expression, while only in 23132/87, JAR, NCI-H510A and THP-1 was the XT-I mRNA expression higher. Nearly equal expression levels were detected in six cell lines. Additionally, to shed light on putative differences in acceptor specificities the acceptor properties of potential acceptor sequences were determined...
January 1, 2010: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/19455420/assay-and-heterologous-expression-in-pichia-pastoris-of-plant-cell-wall-type-ii-membrane-anchored-glycosyltransferases
#18
Bent Larsen Petersen, Jack Egelund, Iben Damager, Kirsten Faber, Jacob Krüger Jensen, Zhang Yang, Eric Paul Bennett, Henrik Vibe Scheller, Peter Ulvskov
Two Arabidopsis xylosyltransferases, designated RGXT1 and RGXT2, were recently expressed in Baculovirus transfected insect cells and by use of the free sugar assay shown to catalyse transfer of D-xylose from UDP-alpha-D-xylose to L-fucose and derivatives hereof. We have now examined expression of RGXT1 and RGXT2 in Pichia pastoris and compared the two expression systems. Pichia transformants, expressing soluble, secreted forms of RGXT1 and RGXT2 with an N- or C-terminal Flag-tag, accumulated recombinant, hyper-glycosylated proteins at levels between 6 and 16 mg protein * L(-1) in the media fractions...
December 2009: Glycoconjugate Journal
https://www.readbyqxmd.com/read/19389916/xylosyltransferase-ii-is-a-significant-contributor-of-circulating-xylosyltransferase-levels-and-platelets-constitute-an-important-source-of-xylosyltransferase-in-serum
#19
Eduard Condac, George L Dale, Diane Bender-Neal, Beatrix Ferencz, Rheal Towner, Myron E Hinsdale
Circulating glycosyltransferases including xylosyltransferases I (XylT1) and II (XylT2) are potential serum biomarkers for various diseases. Understanding what influences the serum activity of these enzymes as well as the sources of these enzymes is important to interpreting the significance of alterations in enzyme activity during disease. This article demonstrates that in the mouse and human the predominant XylT in serum is XylT2. Furthermore, that total XylT levels in human serum are approximately 200% higher than those in plasma due in part to XylT released by platelets during blood clotting in vitro...
August 2009: Glycobiology
https://www.readbyqxmd.com/read/19289103/analysis-of-xylosyltransferase-ii-binding-to-the-anticoagulant-heparin
#20
Javier Carrera Casanova, Michael Ambrosius, Joachim Kuhn, Knut Kleesiek, Christian Götting
The key enzymes in the biosynthetic pathway of glycosaminoglycan production are represented by the human xylosyltransferase I and its isoform II (XylT-I and XylT-II). The glycosaminoglycan heparin interacts with a variety of proteins, thereby regulating their activities, also those of xylosyltransferases. The identification of unknown amino acids responsible for heparin-binding of XylT-II was addressed in this study. Thus, six XylT-II fragments were designed as fusion proteins with MBP and we received soluble and purified MBP/XylT-II from Escherichia coli...
May 22, 2009: Biochemical and Biophysical Research Communications
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