Disease relevance of XYLT1

• Based on the partial amino acid sequence of the purified enzyme from human JAR choriocarcinoma cell culture supernatant we isolated a cDNA encoding XT-I using the degenerate reverse transcriptase-polymerase chain reaction method [1].
• Furthermore, xylosyltransferase activity was correlated with the clinical classification of systemic sclerosis [2].
• Serum XT-I, the novel fibrosis marker, may be useful for the assessment of extracellular matrix alterations and disease activity in PXE [3].
• Elevated xylosyltransferase I activities in pseudoxanthoma elasticum (PXE) patients as a marker of stimulated proteoglycan biosynthesis [3].
• The mean XT-I activities in PXE patients with hypertension were 24% higher than in patients without increased blood pressure (p<0.05) [3].
• In the left and right ventricular samples of dilated cardiomyopathy patients, our data show increased amounts of XT-I mRNA compared with nonfailing controls [4].

High impact information on XYLT1

• Those peptides corresponding to amino acid sequences known to contain glycosaminoglycan-substituted serine residues in the protein were efficient xylosyltransferase acceptors, whereas peptides from sequences with no glycosaminoglycan-substituted serine residues were not [5].
• Here we show evidence that the stem regions were indispensable for Golgi localization of XT-I and XT-II [6].
• Xylosyltransferase I (XT-I) catalyzes the transfer of xylose from UDP-xylose to serine residues in proteoglycan core proteins [6].
• Furthermore, a co-localization of native human XT-I and alpha-mannosidase II could also be demonstrated in untransfected cells [6].
• We expressed both AtXT1 and a second closely related gene, now called AtXT2, in insect cells and demonstrated that both have XT activity for cellopentaose and cellohexaose acceptor substrates [7].

Chemical compound and disease context of XYLT1

• First isolation of human UDP-D-xylose: proteoglycan core protein beta-D-xylosyltransferase secreted from cultured JAR choriocarcinoma cells [8].

Biological context of XYLT1

• A new 3608 bp cDNA fragment encoding a protein of 865 amino acid residues was also isolated by PCR using degenerate primers based on the amino acid sequence of human XT-I [1].
• The human XT-I gene was located on chromosome 16p13.1 using radiation hybrid mapping, and extracts from CHO-K1 cells transfected with the XT-I cDNA in an expression vector exhibited marked XT activity [1].
• Our study demonstrates that over 80% of the nucleotide sequence of the XT-I-cDNA is necessary for expressing a recombinant enzyme with full catalytic activity [9].
• Interestingly, deletion of the single 12 amino acid motif G261KEAISALSRAK272 leads to a loss-of-function XT-I mutant [9].
• METHODS: We screened all XYLT exons in 65 German PXE patients using denaturing high performance liquid chromatography and analysed the influence of the variations on clinical characteristics [10].

Anatomical context of XYLT1

• Exposure of human chondrocytes to colchicine led to a 3-fold decreased level of xylosyltransferase and chondroitin-6-sulfate concentration in cell culture [2].
• Secretion of xylosyltransferase into the extracellular space was determined in cultured human dermal fibroblasts [2].
• Xylosyltransferase activity in seminal plasma of infertile men [11].
• Screening over 1000 extracts from a random plant collection obtained from the Amazon rain forest yielded five plants that stimulated glycosaminoglycan assembly in both wild-type cells and a mutant cell line defective in xylosyltransferase (the first committed enzyme involved in glycosaminoglycan biosynthesis) [12].
• The enzyme responsible for this reaction, UDP-glucuronate carboxy-lyase, co-localized with xylosyltransferase activity in subcellular fractions [13].

Associations of XYLT1 with chemical compounds

• Human UDP-d-xylose:proteoglycan core protein beta-d-xylosyltransferase (EC 2.4.2.26, XT-I) initiates the biosynthesis of glycosaminoglycan chains in proteoglycans by transferring xylose from UDP-xylose to specific serine residues of the core protein [1].
• The properties of binding of XT-I to heparin-beads, the Ki constants for noncompetitive inhibition by heparin, and the activation by protamine were not altered by the generated mutations [14].
• Specific xylosyltransferase activity and chondroitin-6-sulfate concentration decreased in a concentration-dependent manner and in parallel in culture medium and accumulated 5-fold in cell lysates indicating that xylosyltransferase is secreted simultaneously into the extracellular space with chondroitin sulfate proteoglycans [2].
• UDP-D-xylose:proteoglycan core protein beta-D-xylosyltransferase (EC2.4.2.26) is the initial enzyme in the biosynthesis of chondroitin sulfate and dermatan sulfate proteoglycans in fibroblasts and chondrocytes [2].
• Human xylosyltransferase I: functional and biochemical characterization of cysteine residues required for enzymic activity [15].

Other interactions of XYLT1

• A decorin core protein mutant devoid of N-linked oligosaccharide attachment sites will not be secreted by Chinese hamster ovary cells deficient in xylosyltransferase or by parental Chinese hamster ovary wild type cells if the xylosyltransferase recognition sequence is disrupted [16].
• It was possible to improve the overall degree of attachment by mutating Ser472 to glutamic acid (so as to conform Ser474 to the xylosyltransferase acceptor consensus acidic-Gly-Ser-Gly-acidic); however, a significant proportion (approx. 35%) of the total TM still lacked a glycosaminoglycan moiety [17].
• CS-deficient full-length recombinant aggrecan (rbAgg) was produced by chondroitinase ABC treatment, or by expression in the xylosyltransferase-deficient CHO-pgsA745 cell line [18].
• Novel sequence variants in the human xylosyltransferase I gene and their role in diabetic nephropathy [19].
• Localization of glycolipid and glycoprotein glycosyltransferase activities in the isolated Golgi and ER fractions was examined; three glycosyltransferases, i.e., galactosyltransferase, fucosyltransferase, and xylosyltransferase, proved to be almost exclusively confined to the Golgi, whereas the ER fractions contained glycolipid glycosyltransferase [20].

Analytical, diagnostic and therapeutic context of XYLT1

• METHODS: Xylosyltransferase activity was determined in seminal plasma and serum samples of 50 healthy semen donors, 20 infertile men with oligo-, astheno- or teratozoospermia and men after vasectomy [11].
• In addition, the role of the cysteine residues was investigated by site-directed mutagenesis combined with chemical modifications of XT-I by N-phenylmaleimide [15].
• Measurement of fibrosis marker xylosyltransferase I activity by HPLC electrospray ionization tandem mass spectrometry [21].
• A xylosyltransferase of apparent M(r) 38,000 on size-exclusion chromatography was associated with cell expansion and primary wall synthesis [22].
• Molecular cloning and functional expression of beta1, 2-xylosyltransferase cDNA from Arabidopsis thaliana [23].

References