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Information on EC 2.4.1.226 - N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase and Organism(s) Homo sapiens
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2.4.1.226 N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferaseIUBMB Comments
Involved in the biosynthesis of chondroitin and dermatan sulfate. The human chondroitin synthetase is a bifunctional glycosyltransferase, which has the 3-beta-glucuronosyltransferase and 4-beta-N-acetylgalactosaminyltransferase (EC 2.4.1.175) activities required for the synthesis of the chondroitin sulfate disaccharide repeats. Similar chondroitin synthase 'co-polymerases' can be found in Pasteurella multocida and Escherichia coli. There is also another human protein with apparently only the 3-beta-glucuronosyltransferase activity.
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Word Map
- 2.4.1.226
- glycosaminoglycans
- proteoglycans
- tetrasaccharide
- dermatan
-
polymerizing
- csgalnact1
-
hyperelongation
- brachydactyly
-
glcua
-
unsulfated
-
preaxial
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
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=
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[protein]-3-O-(beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine
+
=
+
+
[protein]-3-O-([beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)]n-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine
=
+
[protein]-3-O-(beta-D-GlcA-(1->3)-[beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)]n-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine
Synonyms
chsy1, chondroitin synthase, chgn-2, csgalnact-1, chgn-1, chsy-1, chsy3, chondroitin sulfate synthase 1, csglca-t, glcat-ii, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
chondroitin beta-glucuronyltransferase
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-
-
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chondroitin glucuronyltransaferase II
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-
-
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chondroitin glucuronyltransferase
-
-
-
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chondroitin sulfate glucuronyltransferase
chondroitin sulfate synthase-3
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enzyme possesses dual enzymatic GalNAcT-II (N-acetylgalactosaminyltransferase-II) and GlcAT-II (glucuronyltransferase-II) activities
glucuronyltransferase, uridine diphosphoglucuronate-chondroitin
-
-
-
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UDP-glucuronate:chondroitin glucuronyltransferase
-
-
-
-
additional information
chondroitin sulfate glucuronyltransferase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
UDP-alpha-D-glucuronate + [protein]-3-O-(beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine = UDP + [protein]-3-O-(beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine
UDP-alpha-D-glucuronate + [protein]-3-O-(beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine = UDP + [protein]-3-O-(beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine
transfer to polymer most likely through a beta(1-3) linkage
-
UDP-alpha-D-glucuronate + [protein]-3-O-(beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine = UDP + [protein]-3-O-(beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine
enzyme has dual function possessing both glucuronyltransferase and N-acetylgalactosaminyltransferase activities
UDP-alpha-D-glucuronate + [protein]-3-O-(beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine = UDP + [protein]-3-O-(beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine
enzyme has dual function possessing both glucuronyltransferase and N-acetylgalactosaminyltransferase activities
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glucuronyl group transfer
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-
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glycosyl group transfer
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-
-
-
PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
UDP-alpha-D-glucuronate:[protein]-3-O-(beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine = UDP + [protein]-3-O-(beta-D-GlcA-(1->?3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine 3-beta-glucuronosyltransferase (configuration-inverting)
Involved in the biosynthesis of chondroitin and dermatan sulfate. The human chondroitin synthetase is a bifunctional glycosyltransferase, which has the 3-beta-glucuronosyltransferase and 4-beta-N-acetylgalactosaminyltransferase (EC 2.4.1.175) activities required for the synthesis of the chondroitin sulfate disaccharide repeats. Similar chondroitin synthase 'co-polymerases' can be found in Pasteurella multocida and Escherichia coli. There is also another human protein with apparently only the 3-beta-glucuronosyltransferase activity.
CAS REGISTRY NUMBER
COMMENTARY
176023-59-9
-
269077-98-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
UDP-alpha-D-glucuronate + alpha-thrombomodulin
UDP + beta-D-glucuronosyl-(1,3)-alpha-thrombomodulin
-
-
-
?
UDP-alpha-D-glucuronate + beta-D-glucuronosyl-(1,3)-beta-D-galactosyl-(1,3)-beta-D-galactosyl-1,4-beta-D-xylose-1-O-Gly-Ser-Gly-Glu
UDP + ?
synthetic tetrasaccharide substrate
-
-
?
UDP-alpha-D-glucuronate + beta-D-glucuronosyl-(1,3)-beta-D-galactosyl-(1,3)-beta-D-galactosyl-1,4-beta-D-xylose-1-O-serine
UDP + ?
synthetic tetrasaccharide substrate
-
-
?
UDP-alpha-D-glucuronate + C11-oligosaccharide of chondroitin sulfate A
?
-
-
-
?
UDP-alpha-D-glucuronate + chondroitin sulfate A
UDP + beta-D-glucuronosyl-(1,3)-chondroitin sulfate A
and oligosaccharide of chondroitin sulfate with chain length of C11
-
-
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-galactosaminyl-(1-4)-beta-D-glucuronosyl-proteoglycan
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-galactosaminyl-(1-4)-beta-D-glucuronosyl-proteoglycan
-
-
-
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan
UDP-alpha-D-glucuronic acid + N-acetyl-D-galactosaminyl chondroitin polysaccharide
UDP + beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-chondroitin polysaccharide
polysaccharide substrate used after beta-glucuronidase treatment
-
-
?
UDP-glucuronic acid + chondroitin
UDP + N-acetylchondrosine glucuronic acid beta(1-3)N-acetylgalactosamine
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-
-
?
UDP-glucuronic acid + chondroitin heptasaccharide
?
heptasaccharide having a N-acetylgalactosamine residue at its non-reducing terminus
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-
?
UDP-glucuronic acid + chondroitin sulfate heptasaccharide
?
heptasaccharide having a N-acetylgalactosamine residue at its non-reducing terminus
-
-
?
UDP-alpha-D-glucuronate + chondroitin
UDP + beta-D-glucuronosyl-(1,3)-chondroitin
-
-
-
?
UDP-alpha-D-glucuronate + chondroitin
UDP + beta-D-glucuronosyl-(1,3)-chondroitin
chondroitin polymerization in disaccharide units by glucuronyltransferase and N-acetylgalactosaminyltransferase activities of the enzyme
-
-
?
UDP-alpha-D-glucuronate + chondroitin
UDP + beta-D-glucuronosyl-(1,3)-chondroitin
and oligosaccharide of chondroitin with chain length of C11
-
-
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan
-
-
-
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan
-
-
-
-
?
additional information
?
-
the glucuronic acid transfer rate roughly increases with increasing chain length
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-
?
additional information
?
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the glucuronic acid transfer rate roughly increases with increasing chain length
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-
?
additional information
?
-
no substrates: chondroitin, chondroitin sulfate, dermatan sulfate, N-acetylheparosan, hyaluronan, heparan sulfate, heparin, hyaluronan heptasaccharides
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-
?
additional information
?
-
-
no substrates: chondroitin, chondroitin sulfate, dermatan sulfate, N-acetylheparosan, hyaluronan, heparan sulfate, heparin, hyaluronan heptasaccharides
-
-
?
additional information
?
-
in vitro activity of the recombinant enzyme requires concomitant expression of the chondroitin polymerizing factor ChPF in a fusion protein, mixing of separately expressed proteins does not result in an active complex, overview
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-
?
additional information
?
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-
in vitro activity of the recombinant enzyme requires concomitant expression of the chondroitin polymerizing factor ChPF in a fusion protein, mixing of separately expressed proteins does not result in an active complex, overview
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-
?
additional information
?
-
substrate specificities of enzymes CSGlcAT-II and CSS2 in truncated form
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-
?
additional information
?
-
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substrate specificities of enzymes CSGlcAT-II and CSS2 in truncated form
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-
?
additional information
?
-
-
CSGlcA-T exhibits polymerization activity on alpha-thrombomodulin using alpha-thrombomodulin as acceptor incubated with UDP-Gal-NAc and UDP-GlcUA. The chain length of chondroitin formed by the co-expressed proteins ChSy-1,ChSy-2 (CSS3), or ChPF in various combinations is different
-
-
?
additional information
?
-
CSGlcA-T exhibits polymerization activity on alpha-thrombomodulin using alpha-thrombomodulin as acceptor incubated with UDP-Gal-NAc and UDP-GlcUA. The chain length of chondroitin formed by the co-expressed proteins ChSy-1,ChSy-2 (CSS3), or ChPF in various combinations is different
-
-
?
additional information
?
-
-
polymerization reactions carried out using alpha-thrombomodulin as an acceptor co-incubated with UDP-GalNAc and UDP-GlcA
-
-
?
additional information
?
-
polymerization reactions carried out using alpha-thrombomodulin as an acceptor co-incubated with UDP-GalNAc and UDP-GlcA
-
-
?
additional information
?
-
chondroitin synthase-1 has two glycosyltransferase activities: it acts as a GlcUA and a GalNAc transferase and is responsible for adding repeated disaccharide units to growing chondroitin sulfate chains
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
UDP-alpha-D-glucuronate + chondroitin
UDP + beta-D-glucuronosyl-(1,3)-chondroitin
chondroitin polymerization in disaccharide units by glucuronyltransferase and N-acetylgalactosaminyltransferase activities of the enzyme
-
-
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-galactosaminyl-(1-4)-beta-D-glucuronosyl-proteoglycan
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-galactosaminyl-(1-4)-beta-D-glucuronosyl-proteoglycan
-
-
-
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan
additional information
?
-
chondroitin synthase-1 has two glycosyltransferase activities: it acts as a GlcUA and a GalNAc transferase and is responsible for adding repeated disaccharide units to growing chondroitin sulfate chains
-
-
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan
-
-
-
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan
-
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
17% and 31% as effective as Mn2+ for glucuronyltransferase and N-acetylgalactosaminyltransferase activities, respectively
Mn2+
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
chondroitin synthase-1
co-expressed with chondroitin synthase-1 CSS3 also exhibits polymerase activity
-
chondroitin-polymerizing factor
co-expressed with ChPF (chondroitin-polymerizing factor) enzyme shows chondroitin polymerase activity
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00000004
glucuronyltransferase of recombinant wild-type enzyme secreted from COS-1 cells
0.00000314
glucuronyltransferase of recombinant mutant fusion protein consisting of enzyme and chondroitin polymerizing factor secreted from COS-1 cells
additional information
additional information
-
highest at the middle prenatal stage in the bovine and chicken sera, highest at the late prenatal stage in the rat serum
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
chondroitin sulfate synthase-2, i.e. CSS2; 2 enzymes: CSGlcAT-II and CSS2
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
by in situ hybridization and real time RT-PCR of developing cartilage, CSGal-NAcT-1 exhibits the highest level of expression among other glycosyltransferases involved in chondroitin sulphate synthesis
CHSY1 is frequently upregulated in glioblastoma and correlates with high tumor grade and poor survival
soft tissue sarcomas. Soft tissue sarcoma is a malignant tumor of nonepithelial extraskeletal origin classified by specific, differentiated cell types
additional information
additional information
ChGn-2 expression on early and advanced atherosclerotic lesions, overview
additional information
-
ChGn-2 expression on early and advanced atherosclerotic lesions, overview
additional information
CHSY1 is strongly expressed in myxofibrosarcoma and malignant peripheral nerve sheath tumor compared with other tumors and significantly associated with higher, rather than lower-grade tumors. High expression of CHSY1 is also significantly associated with poorer patient outcomes and higher stages, overview. Enzyme CHSY1 expression correlates with malignant potential of soft tissue sarcomas with myxoid substance
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
CHSY1 is mainly expressed in the paranuclear cytoplasm and strong CS56 staining in the extracellular space, plasma membrane, and cytoplasm of control cells
-
additional information
-
CHSY1 is mainly expressed in the paranuclear cytoplasm and strong CS56 staining in the extracellular space, plasma membrane, and cytoplasm of control cells
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
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
malfunction
missense mutations in the ChGn-1 gene results in an altered amount of chondroitin sulfate proteoglycans
malfunction
two missense mutations occur in the chondroitin N-acetylgalactosaminyltransferase-1 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
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
correlation between clinicopathological features and expression of CS synthases in glioma patients. The changes of cell surface CS and its contribution to malignant growth of glioma cells are analyzed, 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
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 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 selectively regulates the PDGFRA pathway and enhances PDGFRA protein stability in glioblastoma cells
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). CHSS1_HUMAN
802
1
91784
Swiss-Prot
Secretory Pathway (Reliability: 4)
CHSS2_HUMAN
775
0
85467
Swiss-Prot
Secretory Pathway (Reliability: 2)
CHSS3_HUMAN
882
1
100284
Swiss-Prot
Secretory Pathway (Reliability: 3)
CHPF2_HUMAN
772
0
85948
Swiss-Prot
Secretory Pathway (Reliability: 2)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D184A
mutant protein which lacks any glycosyltransferase activity but interacts with other ChSy family members shows that the glycosyltransferase activity of CSGlcA-T plays an important role in chondroitin polymerization
F362S
naturally occuring missense mutation of the enzyme activity-related, highly conserved residue, the mutant protein has a 56% decrease in GalNAcT-II activity and a 55% decrease in GlcAT-II activity compared to the wild-type
S126L
naturally occuring mutation, inactive mutant, the amount of chondroitin sulfate proteoglycans is reduced. In men, multiple sclerosis patients with S126L have a slower disease progression. This cSNP might be associated with the gender differences in clinical course of multiple sclerosis
additional information
additional information
-
adenoviral gene delivery of the enzyme into intervertebral discs of 4-month -old ICR mice displays a substantial increase in the level of chondroitin sulfate biosynthesis
additional information
-
overexpression of CSGlcA-T increases the amount of chondroitin sulfate in HeLa cells, whereas the RNA interference of CSGlcA-T results in a reduction of the amount of chondroitin sulphate in the cells
additional information
overexpression of CSGlcA-T increases the amount of chondroitin sulfate in HeLa cells, whereas the RNA interference of CSGlcA-T results in a reduction of the amount of chondroitin sulphate in the cells
additional information
-
overexpression of CSS3 increases the amount of chondroitin sulfate in HeLa cells, while the RNA interference of CSS3 results in a reduction in the amount of CS in the cells
additional information
overexpression of CSS3 increases the amount of chondroitin sulfate in HeLa cells, while the RNA interference of CSS3 results in a reduction in the amount of CS in the cells
additional information
-
overexpression of the enzyme in chondrocytic cells further enhances chondroitin sulfate biosynthesis but not that of the aggrecan core protein, indicating that the enzyme activity is not saturated in the cells and that aggrecan synthesized in the overexpressing cells is heavier than the native molecule
additional information
two missense mutations in the CHSY1 gene in patients with neuropathy. These mutations are associated with a profound decrease in enzyme activity. Construction of a soluble form of ChSy-1
additional information
both CHSY1 expression and CS56 staining are dramatically decreased in CHSY1-silenced cells
additional information
-
both CHSY1 expression and CS56 staining are dramatically decreased in CHSY1-silenced cells
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
a soluble form of CSGlcA-T is generated by replacing the first 57 amino acids of the protein with a cleavable insulin signal sequence and a protein A IgG-binding domain. The soluble protein is expressed in COS-1 cells as a recombinant protein fused with the protein A IgG-binding domain. The fusion protein secreted into the medium is adsorbed onto IgG-Sepharose beads for purification to eliminate endogenous glycosyltransferases, and then the protein-bound beads are used as an enzyme source
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, expression of putative catalytic domains of CSGlcAT-II and CSS2 in COS-7 cells as FLAG-tagged soluble proteins, which possesses glucuronyltransferase and N-acetylgalactosaminyltransferase activities as the wild-type enzyme
enzyme domain containing beta-3-glycosyltransferase motifs, expressed in COS-7 cells ATCCCRL 1651
gene ChSy-1, genotyping in healthy persons and multiple sclerosis patients, recombinant expression of wild-type and mutant enzymes in COS-1 cells
gene CHSY1, soluble forms of wild-type and mutant ChSy-1 is heterologously expressed in COS-1 cells, the recombinant enzymes are secreted to the medium, quantitative real-time RT-PCR enzyme expression analysis
genetic organization, coexpression of enzyme and chondroitin polymerizing factor as fusion protein in COS-1 cells, secretion into the cell culture medium
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
CSGalNAcT-1 plays a critical role in chondroitin sulfate biosynthesis in cartilage
medicine
CHSY1 expression is closely associated with malignant potential of soft tissue sarcomas with myxoid substance
medicine
gene ChGn-2 may serve as a plausible target to treat atherosclerotic-related diseases in humans
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kitagawa, H.; Ujikawa, M.; Sugahara, K.
Developmental changes in serum UDP-GlcA:chondroitin glucuronyltransferase activity
J. Biol. Chem.
271
6583-6585
1996
Bos taurus, Gallus gallus gallus, Homo sapiens, Rattus norvegicus
Gotoh, M.; Yada, T.; Sato, T.; Akashima, T.; Iwasaki, H.; Mochizuki, H.; Inaba, N.; Togayachi, A.; Kudo, T.; Watanabe, H.; Kimata, K.; Narimatsu, H.
Molecular cloning and characterization of a novel chondroitin sulfate glucuronyltransferase that transfers glucuronic acid to N-acetylgalactosamine
J. Biol. Chem.
277
38179-38188
2002
Homo sapiens (Q9P2E5), Homo sapiens
Kitagawa, H.; Izumikawa, T.; Uyama, T.; Sugahara, K.
Molecular cloning of a chondroitin polymerizing factor that cooperates with chondroitin synthase for chondroitin polymerization
J. Biol. Chem.
278
23666-23671
2003
Homo sapiens (Q8IZ52), Homo sapiens
Yada, T.; Gotoh, M.; Sato, T.; Shionyu, M.; Go, M.; Kaseyama, H.; Iwasaki, H.; Kikuchi, N.; Kwon, Y.D.; Togayachi, A.; Kudo, T.; Watanabe, H.; Narimatsu, H.; Kimata, K.
Chondroitin sulfate synthase-2. Molecular cloning and characterization of a novel human glycosyltransferase homologous to chondroitin sulfate glucuronyltransferase, which has dual enzymatic activities
J. Biol. Chem.
278
30235-30247
2003
Homo sapiens (Q8IZ52), Homo sapiens
Sakai, K.; Kimata, K.; Sato, T.; Gotoh, M.; Narimatsu, H.; Shinomiya, K.; Watanabe, H.
Chondroitin sulfate N-acetylgalactosaminyltransferase-1 plays a critical role in chondroitin sulfate synthesis in cartilage
J. Biol. Chem.
282
4152-4161
2007
Homo sapiens, Mus musculus
Izumikawa, T.; Uyama, T.; Okuura, Y.; Sugahara, K.; Kitagawa, H.
Involvement of chondroitin sulfate synthase-3 (chondroitin synthase-2) in chondroitin polymerization through its interaction with chondroitin synthase-1 or chondroitin-polymerizing factor
Biochem. J.
403
545-552
2007
Homo sapiens, Homo sapiens (A2V663)
Izumikawa, T.; Saigoh, K.; Shimizu, J.; Tsuji, S.; Kusunoki, S.; Kitagawa, H.
A chondroitin synthase-1 (ChSy-1) missense mutation in a patient with neuropathy impairs the elongation of chondroitin sulfate chains initiated by chondroitin N-acetylgalactosaminyltransferase-1
Biochim. Biophys. Acta
1830
4806-4812
2013
Homo sapiens (Q86X52)
Saigoh, K.; Yoshimura, S.; Izumikawa, T.; Miyata, S.; Tabara, Y.; Matsushita, T.; Miki, T.; Miyamoto, K.; Hirano, M.; Kitagawa, H.; Kira, J.I.; Kusunoki, S.
Chondroitin sulfate beta-1,4-N-acetylgalactosaminyltransferase-1 (ChGn-1) polymorphism: association with progression of multiple sclerosis
Neurosci. Res.
108
55-59
2016
Homo sapiens (Q86X52), Homo sapiens
Adhikara, I.M.; Yagi, K.; Mayasari, D.S.; Ikeda, K.; Kitagawa, H.; Miyata, O.; Igarashi, M.; Hatakeyama, K.; Asada, Y.; Hirata, K.I.; Emoto, N.
Chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell migration
Biochem. Biophys. Res. Commun.
509
89-95
2019
Homo sapiens (Q8IZ52), Homo sapiens, Mus musculus (Q6IQX7), Mus musculus, Mus musculus C57BL/6J (Q6IQX7)
Momose, T.; Yoshimura, Y.; Harumiya, S.; Isobe, K.; Kito, M.; Fukushima, M.; Kato, H.; Nakayama, J.
Chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance
Hum. Pathol.
50
15-23
2016
Homo sapiens (Q86X52)
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