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evolution
the enzyme is a member of the ChSy family
evolution
the enzyme belongs to the GH family 2. The sequence from the photosynthetic green sulfur bacteria, Chlorobium phaeobacteroides DSM 266, which is very similar (about 62% identical) to the open reading frames of known bifunctional chondroitin synthases (Pasteurella multocida PmCS and Escherichia coli KfoC) some segments are strikingly conserved amongst the three proteins. Recombinant Escherichia coli-derived Chlorobium enzyme preparations are found to possess bona fide chondroitin synthase activity in vitro. This catalyst, CpCS, has a more promiscuous acceptor usage than the prototypical PmCS, which may be of utility in novel chimeric GAG syntheses. The finding of such a similar chondroitin synthase enzyme in Chlorobium phaeobacteroides is unexpected for several reasons including (a) a free-living nonpathogenic organism should not require an animal self molecule for protection, (b) the Proteobacteria and the green sulfur bacterial lineages diverged 2.5-3 billion years ago and (c) the ecological niches of these bacteria are not thought to overlap substantially to facilitate horizontal gene transfer. But this Chlorobium has somehow acquired the gene via horizontal gene transfer as the probability of such close functional evolutionary convergence seems a less likely alternative
evolution
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the enzyme belongs to the GH family 2. The sequence from the photosynthetic green sulfur bacteria, Chlorobium phaeobacteroides DSM 266, which is very similar (about 62% identical) to the open reading frames of known bifunctional chondroitin synthases (Pasteurella multocida PmCS and Escherichia coli KfoC) some segments are strikingly conserved amongst the three proteins. Recombinant Escherichia coli-derived Chlorobium enzyme preparations are found to possess bona fide chondroitin synthase activity in vitro. This catalyst, CpCS, has a more promiscuous acceptor usage than the prototypical PmCS, which may be of utility in novel chimeric GAG syntheses. The finding of such a similar chondroitin synthase enzyme in Chlorobium phaeobacteroides is unexpected for several reasons including (a) a free-living nonpathogenic organism should not require an animal self molecule for protection, (b) the Proteobacteria and the green sulfur bacterial lineages diverged 2.5-3 billion years ago and (c) the ecological niches of these bacteria are not thought to overlap substantially to facilitate horizontal gene transfer. But this Chlorobium has somehow acquired the gene via horizontal gene transfer as the probability of such close functional evolutionary convergence seems a less likely alternative
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malfunction
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knockdown of chondroitin expression results in the inhibition of fibroblast proliferation, adhesion and migration, as well as an increasing the number of cells that were arrested in the G2/M phase
malfunction
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CSS2 knockout mice are viable and fertile, exhibiting no overt morphological abnormalities or osteoarthritis, but their cartilage contains chondroitin sulfate chains with a shorter length and although at a similar number to wild-type. CSS2 knockout chondrocyte culture systems, together with siRNA of CSS1, reveal the presence of two CS chain species in length, suggesting two steps of CS chain polymerization; i.e., elongation from the linkage region up to Mr of about 10,00 and further extension
malfunction
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overexpression of ChGn-2 increases the length and amount of chondroitin sulfate chains in L cells, but not in sog9 mutant cells. Knockdown of ChGn-2 results in a decrease in the amount of CS in L cells in a manner proportional to ChGn-2 expression levels, whereas the introduction of mutated ChGn-2 lacking enzyme activity fails to increase the amount of chondroitin sulfate
malfunction
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reduced glucuronyltransferase activity for splice variant CSS2B and no polymerizing activity for CSS2B co-expressed with CSS1, in contrast to splice variant CSS2A co-expressed with CSS1
malfunction
missense mutations in the ChGn-1 gene results in an altered amount of chondroitin sulfate proteoglycans
malfunction
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silencing of CHSY1 decreases sulfated glycosaminoglycan accumulation in nucleus pulposus cells induced by TGF-beta
malfunction
two missense mutations occur in the CHSY1 gene in patients with neuropathy. These mutations are associated with a profound decrease in enzyme activity. The chondroitin synthase-1 F362S mutation in a patient with neuropathy results in a decrease in chondroitin polymerization activity and the mutant protein is defective in regulating the number of chondroitin sulfate chains via CHSY1. The progression of peripheral neuropathies may result from defects in these regulatory systems
malfunction
analysis of the craniofacial morphology in chondroitin sulfate N-acetylgalactosaminyltransferase-1 (T1) gene knockout (KO) mice. T1KO mice show the impaired intramembranous ossification in the skull, and the final skull shape of adult mice include a shorter face, higher and broader calvaria than wild-type. Some of T1KO mice exhibit severe facial developmental defects, such as eye defects and cleft lip and palate, causing embryonic lethality. At the postnatal stages, T1KO mice with severely reduced chondroitin sulfate (CS) amounts show malocclusion, general skeletal dysplasia and skin hyperextension, closely resembling Ehlers-Danlos syndrome-like connective tissue disorders. The production of collagen type 1 is significantly downregulated in T1KO mice, and the deposition of CS-binding molecules, Wnt3a, is decreased with CS in extracellular matrices. The collagen fibers are irregular and aggregated, and connective tissues are dysorganized in the skin and calvaria of T1KO mice
malfunction
chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell (ASMC) migration through attenuating PDGFR phosphorylation. Effects of CHPF gene deletion on the development of atherosclerosis, overview
malfunction
chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell migration. Effects of ChGn-2 gene deletion on the development of atherosclerosis, overview
malfunction
correlation between clinicopathological features and expression of CS synthases in glioma patients. We explore the changes of cell surface CS and its contribution to malignant growth of glioma cells, by manipulating CS Synthase 1 (CHSY1) expression. Overexpression of CHSY1 inhibits PDGF-triggered decrease in PDGFRA levels, whereas CHSY1 knockdown accelerates PDGFRA decrease following PDGF stimulation. PDGFRA is highly expressed on the cell membrane of CHSY1-overexpressing GL261 tumor tissue sections. PDGFRA inhibition reverses CHSY1-mediated tumor growth in vitro and in vivo
malfunction
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reduced glucuronyltransferase activity for splice variant CSS2B and no polymerizing activity for CSS2B co-expressed with CSS1, in contrast to splice variant CSS2A co-expressed with CSS1
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malfunction
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chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell migration. Effects of ChGn-2 gene deletion on the development of atherosclerosis, overview
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metabolism
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CSS1 and CSS2 differently contribute to chondroitin sulfate biosynthesis, mechanism of chondroitin sulfate biosynthesis, overview. CSS1 participates in both the chondroitin sulfate chain initiation and polymerization, and CSS2 participates in the polymerization, especially in further extension
metabolism
the biosynthesis of chondroitin sulfate (CS) chains begins with the formation of a link between N-acetylgalactosamine (GalNAc) and a common tetrasaccharide structure at a serine residue on the core protein. The next step (polymerization) is catalyzed by a group of bifunctional enzymes that have beta1-3 glucuronosyltransferase and beta1-4 N-acetylgalactosaminyltransferase activities. A single CS chain can consist of up to 50 repeating GlcA-GalNAc subunits, which are modified with sulfate groups at various positions. Three bifunctional CS synthases, CHSY1, CHPF (CHSY2), and CHSY3, control polymerization of CS chains
physiological function
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chondroitin 4-O-sulfotransferase-1, C4ST-1 regulates the chain length and amount of chondroitin sulfate in co-operation with ChGn-2 the enzymes play a critical role in chondroitin sulfate chain elongation
physiological function
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CSS2 is involved in elongation of chondroitin sulfate chains. Splice variant CSS2A facilitates chondroitin sulfate biosynthesis, while splice variant CSS2B inhibits it, molecular modeling and mechanisms of chondroitin sulfate biosynthesis regulation, overview. The ratio of CSS2 variants correlates with age-dependent change of chondroitin sulfate chain length in brain of mice
physiological function
ChGn-1 is a key enzyme for production of chondroitin sulfate proteoglycans
physiological function
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chondroitin sulfate synthase 1 (CHSY1) is a glycosyltransferases involved in the biosynthesis of chondroitin and dermatan sulfate glycosaminoglycan. CHSY1 possesses dual glucuronyl-transferase and galactosaminyl-transferase activity. It can promote the transfer of both GlcUA and GalNAc from their donors UDP-GlcUA and UDP-GalNAc, respectively, to the non-reducing end of the chondroitin polymer, resulting in the elongating and accumulation of glycosaminoglycans
physiological function
chondroitin sulfate synthase 1 (CHSY1) is the key biosynthetic enzyme forming the repeating chondroitin sulfate backbone disaccharide structure [4GlcAbeta1-3GalNAcbeta1], and polymerization of chondroitin chain by CHSY1 requires chondroitin polymerizing factors, including CHPF and CHPF2. The bifunctional enzyme CHSY1 exhibits both GlcAT-II and GalNAc-II activities
physiological function
the enzyme initiates the elongation of chondroitin sulfate chains
physiological function
chondroitin sulfate (CS) regulates the shape of the craniofacial skeleton by modulating connective tissue organization
physiological function
chondroitin sulfate N-acetylgalactosaminyltransferase-2 (ChGn-2) is a vital Golgi transferase that participates in enzymatic elongation of GAGs. ChGn-2 is functionally involved in the progression of atherosclerosis both in its early and advanced stages. Crucial contributions of ChGn-2 for LDL retention in the intima. Platelet-derived growth factor (PDGF) signaling is heavily involved in the development of plaques and directly regulates SMCs via platelet-derived growth factor receptor, PDGFR-beta, phosphorylation to promote phenotypic changes including smooth muscle cell migration, enzyme chondroitin sulfate N-acetylgalactosaminyltransferase-2 has a regulatory function
physiological function
chondroitin sulfate N-acetylgalactosaminyltransferase-2 (ChGn-2) is a vital Golgi transferase that participates in enzymatic elongation of GAGs. ChGn-2 is functionally involved in the progression of atherosclerosis both in its early and advanced stages. Crucial contributions of ChGn-2 for LDL retention in the intima. Platelet-derived growth factor (PDGF) signaling is heavily involved in the development of plaques and directly regulates SMCs via platelet-derived growth factor receptor, PDGFR-beta, phosphorylation to promote phenotypic changes including smooth muscle cell migration, enzyme chondroitin sulfate N-acetylgalactosaminyltransferase-2 has a regulatory function
physiological function
CHSY1 selectively modulates platelet derived growth factor receptor alpha (PDGFRA) signaling, and that survival of a mouse model of a CHSY1-expressing tumor is increased by using a PDGFR inhibitor. CHSY1 mediates CS formation in glioma cells. CHSY1 is a crucial enzyme to modulate CS formation in GBM cells in vitro. CHSY1 is a crucial enzyme to modulate CS formation in GBM cells in vitro. CHSY1 selectively regulates the PDGFRA pathway and enhances PDGFRA protein stability in glioblastoma cells
physiological function
the chondroitin synthase (ApCS) is a bifunctional enzyme catalyzing the elongation of the chondroitin chain by alternatively transferring the glucuronic acid (GlcA) and N-acetyl-D-galactosamine (GalNAc) residues from their nucleotide forms to the non-reducing ends of the saccharide chains
physiological function
the glycosyltransferase chondroitin sulfate synthase 1 (CHSY1) specifically functions in biosynthesis of the glycans chondroitin sulfate. The bifunctional CHSY1 exhibits both GlcAT-II and GalNAc-II activities, thus forming the GlcA-GalNAc disaccharide structure specific for chondroitin sulfate
physiological function
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the chondroitin synthase (ApCS) is a bifunctional enzyme catalyzing the elongation of the chondroitin chain by alternatively transferring the glucuronic acid (GlcA) and N-acetyl-D-galactosamine (GalNAc) residues from their nucleotide forms to the non-reducing ends of the saccharide chains
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physiological function
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CSS2 is involved in elongation of chondroitin sulfate chains. Splice variant CSS2A facilitates chondroitin sulfate biosynthesis, while splice variant CSS2B inhibits it, molecular modeling and mechanisms of chondroitin sulfate biosynthesis regulation, overview. The ratio of CSS2 variants correlates with age-dependent change of chondroitin sulfate chain length in brain of mice
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physiological function
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the chondroitin synthase (ApCS) is a bifunctional enzyme catalyzing the elongation of the chondroitin chain by alternatively transferring the glucuronic acid (GlcA) and N-acetyl-D-galactosamine (GalNAc) residues from their nucleotide forms to the non-reducing ends of the saccharide chains
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physiological function
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chondroitin sulfate N-acetylgalactosaminyltransferase-2 (ChGn-2) is a vital Golgi transferase that participates in enzymatic elongation of GAGs. ChGn-2 is functionally involved in the progression of atherosclerosis both in its early and advanced stages. Crucial contributions of ChGn-2 for LDL retention in the intima. Platelet-derived growth factor (PDGF) signaling is heavily involved in the development of plaques and directly regulates SMCs via platelet-derived growth factor receptor, PDGFR-beta, phosphorylation to promote phenotypic changes including smooth muscle cell migration, enzyme chondroitin sulfate N-acetylgalactosaminyltransferase-2 has a regulatory function
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additional information
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either of CSS2A, CSS2B, and CSS1/ChSy-1 heterogeneously and homogeneously interact with each other, suggesting that they form a complex of multimers
additional information
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the enzyme occurs in a heterooligomer complex, chondroitin sulfate synthase-2 (CSS2)/chondroitin polymerizing factor
additional information
structure-function relationship, and structure comparisons with the bifunctional chondroitin synthases from Pasteurella multocida (PmCS) and Escherichia coli (KfoC), overview
additional information
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structure-function relationship, and structure comparisons with the bifunctional chondroitin synthases from Pasteurella multocida (PmCS) and Escherichia coli (KfoC), overview
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