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Information on EC 2.4.1.226 - N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase
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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 expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
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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, cs n-acetylgalactosaminyltransferase-1, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AcbD
ApCS
ChGn-2
chondroitin beta-glucuronyltransferase
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chondroitin glucuronyltransaferase II
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chondroitin glucuronyltransferase
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chondroitin sulfate glucuronyltransferase
chondroitin sulfate N-acetylgalactosaminyltransferase-1
chondroitin sulfate N-acetylgalactosaminyltransferase-2
chondroitin sulfate synthase 1
chondroitin sulfate synthase-3
-
enzyme possesses dual enzymatic GalNAcT-II (N-acetylgalactosaminyltransferase-II) and GlcAT-II (glucuronyltransferase-II) activities
chondroitin synthase
CHSY1
CSGalNAcT-1
CSGlcA-T
GlcAT-II
glucuronyltransferase, uridine diphosphoglucuronate-chondroitin
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glucuronyltransferase-II
UDP-glucuronate:chondroitin glucuronyltransferase
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additional information
chondroitin sulfate glucuronyltransferase
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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)]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 = UDP + [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
(2)
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-
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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 the acceptor through a beta-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
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
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
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
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
-
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
(1)
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glucuronyl group transfer
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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.
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CAS REGISTRY NUMBER
COMMENTARY
176023-59-9
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269077-98-7
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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
NDP-glucose + 3-phospho-D-glycerate
NDP + 2-O-(alpha-D-glucopyranosyl)-3-phospho-D-glycerate
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-GalNAc + 4-nitrophenyl D-glucuronide
UDP + 4-nitrophenyl 4-O-(N-acetyl-alpha-D-glucosaminyl)-D-glucuronide
UDP-glucuronic acid + chondroitin
UDP + N-acetylchondrosine glucuronic acid beta(1-3)N-acetylgalactosamine
UDP-glucuronic acid + chondroitin heptasaccharide
?
heptasaccharide having a N-acetylgalactosamine residue at its non-reducing terminus
-
-
?
UDP-glucuronic acid + chondroitin sulfate heptasaccharide
?
heptasaccharide having a N-acetylgalactosamine residue at its non-reducing terminus
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-
?
NDP-glucose + 3-phospho-D-glycerate
NDP + 2-O-(alpha-D-glucopyranosyl)-3-phospho-D-glycerate
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-
-
?
NDP-glucose + 3-phospho-D-glycerate
NDP + 2-O-(alpha-D-glucopyranosyl)-3-phospho-D-glycerate
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-
-
?
NDP-glucose + 3-phospho-D-glycerate
NDP + 2-O-(alpha-D-glucopyranosyl)-3-phospho-D-glycerate
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-
-
?
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
-
-
-
?
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-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-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
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-
-
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?
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
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chondroitin sulfate A-8, chondroitin sulfate C-8,chondroitin-8, and GlcUAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-methoxy-phenyl as acceptor substrates
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?
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
-
chondroitin sulfate A-8, chondroitin sulfate C-8,chondroitin-8, and GlcUAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-methoxy-phenyl as acceptor substrates
-
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?
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
-
-
-
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?
UDP-GalNAc + 4-nitrophenyl D-glucuronide
UDP + 4-nitrophenyl 4-O-(N-acetyl-alpha-D-glucosaminyl)-D-glucuronide
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-
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?
UDP-GalNAc + 4-nitrophenyl D-glucuronide
UDP + 4-nitrophenyl 4-O-(N-acetyl-alpha-D-glucosaminyl)-D-glucuronide
-
-
-
?
UDP-GalNAc + 4-nitrophenyl D-glucuronide
UDP + 4-nitrophenyl 4-O-(N-acetyl-alpha-D-glucosaminyl)-D-glucuronide
-
-
-
?
UDP-glucuronic acid + chondroitin
UDP + N-acetylchondrosine glucuronic acid beta(1-3)N-acetylgalactosamine
-
-
-
?
UDP-glucuronic acid + chondroitin
UDP + N-acetylchondrosine glucuronic acid beta(1-3)N-acetylgalactosamine
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-
-
-
?
UDP-glucuronic acid + chondroitin
UDP + N-acetylchondrosine glucuronic acid beta(1-3)N-acetylgalactosamine
-
-
-
?
UDP-glucuronic acid + chondroitin
UDP + N-acetylchondrosine glucuronic acid beta(1-3)N-acetylgalactosamine
-
-
-
?
UDP-glucuronic acid + chondroitin
UDP + N-acetylchondrosine glucuronic acid beta(1-3)N-acetylgalactosamine
-
-
-
?
additional information
?
-
GlcA with a para-nitrophenyl group can serve as the acceptor for ApCS. The enzyme shows a stringent donor tolerance when the acceptor is as small as this monosaccharide. Ligand/substrate interaction analysis via surface plasmon resonance (SPR) analysis. Substrate specificity, overview
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additional information
?
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GlcA with a para-nitrophenyl group can serve as the acceptor for ApCS. The enzyme shows a stringent donor tolerance when the acceptor is as small as this monosaccharide. Ligand/substrate interaction analysis via surface plasmon resonance (SPR) analysis. Substrate specificity, overview
-
-
-
additional information
?
-
GlcA with a para-nitrophenyl group can serve as the acceptor for ApCS. The enzyme shows a stringent donor tolerance when the acceptor is as small as this monosaccharide. Ligand/substrate interaction analysis via surface plasmon resonance (SPR) analysis. Substrate specificity, overview
-
-
-
additional information
?
-
GlcA with a para-nitrophenyl group can serve as the acceptor for ApCS. The enzyme shows a stringent donor tolerance when the acceptor is as small as this monosaccharide. Ligand/substrate interaction analysis via surface plasmon resonance (SPR) analysis. Substrate specificity, overview
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additional information
?
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further substrates: chondroitin heptaserine, pentaserine, non-sulfated odd-numbered oligosaccharides with a N-acetylgalactosamine residue at the non-reducing terminus except for a trisaccharide
-
-
?
additional information
?
-
-
no substrates: a trisaccharide-serine, an alpha-N-acetylgalactosamine-capped pentasaccharide-serine
-
-
?
additional information
?
-
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the glucuronic acid transfer rate roughly increases with increasing chain length
-
-
?
additional information
?
-
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6-O-sulfation of non-reducing terminal N-acetylgalactosamine markedly enhances glucuronic acid transfer
-
-
?
additional information
?
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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
-
-
?
additional information
?
-
no substrates: chondroitin, chondroitin sulfate, dermatan sulfate, N-acetylheparosan, hyaluronan, heparan sulfate, heparin, hyaluronan heptasaccharides
-
-
?
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
?
-
-
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
-
-
?
additional information
?
-
substrate specificities of enzymes CSGlcAT-II and CSS2 in truncated form
-
-
?
additional information
?
-
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substrate specificities of enzymes CSGlcAT-II and CSS2 in truncated form
-
-
?
additional information
?
-
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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
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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
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-
?
additional information
?
-
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polymerization reactions carried out using alpha-thrombomodulin as an acceptor co-incubated with UDP-GalNAc and UDP-GlcA
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-
?
additional information
?
-
polymerization reactions carried out using alpha-thrombomodulin as an acceptor co-incubated with UDP-GalNAc and UDP-GlcA
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?
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
-
-
?
additional information
?
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CHSY1, CHSY2 and CHSY3 possess dual, glucuronyltransferase and galactosaminyltransferase enzymatic activities, while the CSGlcA-T acts only by transferring glucuronic acid
-
-
?
additional information
?
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CSS1, CSS2, and CSS3 contain two glycosyltransferase domains, beta-3 domain at the N-terminal region and beta-4 domain at the C-terminal region and exhibit dual enzymatic activities of N-acetylgalactosaminyltransferase-II, GalNAcTII, and glucuronyltransferase-II, GlcAT-II. Chondroitin sulfate glucuronyltransferase, similarly containing two glycosyltransferase domains, shows only GlcAT-I activity, EC 2.4.1.135
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-
?
additional information
?
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CSS2A exhibits both GalNAcT-II and GlcAT-II activities, CSS2B also shows both GalNAcT-II and GlcAT-II activities, but they are 82.8% and 26.5% that of CSS2A, respectively
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?
additional information
?
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-
CSS1, CSS2, and CSS3 contain two glycosyltransferase domains, beta-3 domain at the N-terminal region and beta-4 domain at the C-terminal region and exhibit dual enzymatic activities of N-acetylgalactosaminyltransferase-II, GalNAcTII, and glucuronyltransferase-II, GlcAT-II. Chondroitin sulfate glucuronyltransferase, similarly containing two glycosyltransferase domains, shows only GlcAT-I activity, EC 2.4.1.135
-
-
?
additional information
?
-
-
CSS2A exhibits both GalNAcT-II and GlcAT-II activities, CSS2B also shows both GalNAcT-II and GlcAT-II activities, but they are 82.8% and 26.5% that of CSS2A, respectively
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-
?
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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
NDP-glucose + 3-phospho-D-glycerate
NDP + 2-O-(alpha-D-glucopyranosyl)-3-phospho-D-glycerate
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
NDP-glucose + 3-phospho-D-glycerate
NDP + 2-O-(alpha-D-glucopyranosyl)-3-phospho-D-glycerate
-
-
-
?
NDP-glucose + 3-phospho-D-glycerate
NDP + 2-O-(alpha-D-glucopyranosyl)-3-phospho-D-glycerate
-
-
-
?
NDP-glucose + 3-phospho-D-glycerate
NDP + 2-O-(alpha-D-glucopyranosyl)-3-phospho-D-glycerate
-
-
-
?
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-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-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-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-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
-
-
?
additional information
?
-
-
CHSY1, CHSY2 and CHSY3 possess dual, glucuronyltransferase and galactosaminyltransferase enzymatic activities, while the CSGlcA-T acts only by transferring glucuronic acid
-
-
?
additional information
?
-
-
CSS1, CSS2, and CSS3 contain two glycosyltransferase domains, beta-3 domain at the N-terminal region and beta-4 domain at the C-terminal region and exhibit dual enzymatic activities of N-acetylgalactosaminyltransferase-II, GalNAcTII, and glucuronyltransferase-II, GlcAT-II. Chondroitin sulfate glucuronyltransferase, similarly containing two glycosyltransferase domains, shows only GlcAT-I activity, EC 2.4.1.135
-
-
?
additional information
?
-
-
CSS1, CSS2, and CSS3 contain two glycosyltransferase domains, beta-3 domain at the N-terminal region and beta-4 domain at the C-terminal region and exhibit dual enzymatic activities of N-acetylgalactosaminyltransferase-II, GalNAcTII, and glucuronyltransferase-II, GlcAT-II. Chondroitin sulfate glucuronyltransferase, similarly containing two glycosyltransferase domains, shows only GlcAT-I activity, EC 2.4.1.135
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
17% and 31% as effective as Mn2+ for glucuronyltransferase and N-acetylgalactosaminyltransferase activities, respectively
Mg2+
Mn2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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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
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Atherosclerosis
Chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell migration.
Atherosclerosis
Chondroitin Sulfate N-acetylgalactosaminyltransferase-2 Impacts Foam Cell Formation and Atherosclerosis by Altering Macrophage Glycosaminoglycan Chain.
Atherosclerosis
Correlation of C4ST-1 and ChGn-2 expression with chondroitin sulfate chain elongation in atherosclerosis.
Brachydactyly
A FURTHER PATIENT OF PURE 15q DELETION: CLINICAL AND MOLECULAR CYTOGENETIC FINDINGS.
Brachydactyly
A novel CHSY1 gene mutation underlies Temtamy preaxial brachydactyly syndrome in a Pakistani family.
Brachydactyly
Chondroitin sulfate synthase 1 (Chsy1) is required for bone development and digit patterning.
Brachydactyly
Loss of CHSY1, a secreted FRINGE enzyme, causes syndromic brachydactyly in humans via increased NOTCH signaling.
Brachydactyly
Temtamy preaxial brachydactyly syndrome is caused by loss-of-function mutations in chondroitin synthase 1, a potential target of BMP signaling.
Carcinogenesis
CHSY1 promoted proliferation and suppressed apoptosis in colorectal cancer through regulation of the NF?B and/or caspase-3/7 signaling pathway.
Carcinoma, Hepatocellular
CHSY1 promotes aggressive phenotypes of hepatocellular carcinoma cells via activation of the hedgehog signaling pathway.
Colorectal Neoplasms
Chondroitin synthases I, II, III and chondroitin sulfate glucuronyltransferase expression in colorectal cancer.
Colorectal Neoplasms
CHSY1 promoted proliferation and suppressed apoptosis in colorectal cancer through regulation of the NF?B and/or caspase-3/7 signaling pathway.
Craniofacial Abnormalities
Craniofacial abnormality with skeletal dysplasia in mice lacking chondroitin sulfate N-acetylgalactosaminyltransferase-1.
Encephalomyelitis
Chondroitin sulfate N-acetylgalactosyltransferase-1 knockout shows milder phenotype in experimental autoimmune encephalomyelitis than in wild type.
Encephalomyelitis, Autoimmune, Experimental
Chondroitin sulfate N-acetylgalactosyltransferase-1 knockout shows milder phenotype in experimental autoimmune encephalomyelitis than in wild type.
Glioblastoma
Chondroitin sulfate synthase 1 enhances proliferation of glioblastoma by modulating PDGFRA stability.
Glioblastoma
Loss of CHSY1, a secreted FRINGE enzyme, causes syndromic brachydactyly in humans via increased NOTCH signaling.
Glioma
Chondroitin sulfate synthase 1 enhances proliferation of glioblastoma by modulating PDGFRA stability.
Glioma
Tumor-dependent effects of proteoglycans and various glycosaminoglycan synthesizing enzymes and sulfotransferases on patients' outcome.
Hearing Loss
Temtamy preaxial brachydactyly syndrome is caused by loss-of-function mutations in chondroitin synthase 1, a potential target of BMP signaling.
Intervertebral Disc Degeneration
Chondroitin synthase-3 regulates nucleus pulposus degeneration through actin-induced YAP signaling.
Joint Instability
Chondroitin Sulfate N-acetylgalactosaminylTransferase-1 (CSGalNAcT-1) Deficiency Results in a Mild Skeletal Dysplasia and Joint Laxity.
Lymphoma, B-Cell
CHSY1 promoted proliferation and suppressed apoptosis in colorectal cancer through regulation of the NF?B and/or caspase-3/7 signaling pathway.
Melanoma
The Dietary Supplement Chondroitin-4-Sulfate Exhibits Oncogene-Specific Pro-tumor Effects on BRAF V600E Melanoma Cells.
Multiple Sclerosis
Chondroitin sulfate ?-1,4-N-acetylgalactosaminyltransferase-1 (ChGn-1) polymorphism: Association with progression of multiple sclerosis.
Neoplasm Metastasis
CHSY1 promotes aggressive phenotypes of hepatocellular carcinoma cells via activation of the hedgehog signaling pathway.
Neoplasms
Chondroitin sulfate synthase 1 enhances proliferation of glioblastoma by modulating PDGFRA stability.
Neoplasms
Chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance.
Neoplasms
CHSY1 is upregulated and acts as tumor promotor in gastric cancer through regulating cell proliferation, apoptosis, and migration.
Neoplasms
CHSY1 promoted proliferation and suppressed apoptosis in colorectal cancer through regulation of the NF?B and/or caspase-3/7 signaling pathway.
Neoplasms
CHSY1 promotes aggressive phenotypes of hepatocellular carcinoma cells via activation of the hedgehog signaling pathway.
Neurofibrosarcoma
Chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance.
Sarcoma
Chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance.
Spinal Cord Injuries
Chondroitin sulfate ?-1,4-N-acetylgalactosaminyltransferase-1 (ChGn-1) polymorphism: Association with progression of multiple sclerosis.
Spinal Cord Injuries
Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury.
Stomach Neoplasms
CHSY1 is upregulated and acts as tumor promotor in gastric cancer through regulating cell proliferation, apoptosis, and migration.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
-
Michaelis-Menten kinetics
-
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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
additional information
-
highest at the middle prenatal stage in the bovine and chicken sera, highest at the late prenatal stage in the rat serum
additional information
-
highest at the middle prenatal stage in the bovine and chicken sera, highest at the late prenatal stage in the rat serum
additional information
-
highest at the middle prenatal stage in the bovine and chicken sera, highest at the late prenatal stage in the rat serum
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.2
6.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
chondroitin sulfate synthase-2, i.e. CSS2; 2 enzymes: CSGlcAT-II and CSS2
SwissProt
brenda
further cDNA: Kazusa DNA Research Institute number KIAA1402
SwissProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
CHSY1 is frequently upregulated in glioblastoma and correlates with high tumor grade and poor survival
brenda
soft tissue sarcomas. Soft tissue sarcoma is a malignant tumor of nonepithelial extraskeletal origin classified by specific, differentiated cell types
brenda
additional information
-
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
brenda
-
in heterozygote and homozygote aggrecan-null cartilage where aggrecan transcription is decreased, CSGal-NAcT-1 transcription diminishs accordingly
brenda
additional information
ChGn-2 expression on early and advanced atherosclerotic lesions, overview
brenda
additional information
-
ChGn-2 expression on early and advanced atherosclerotic lesions, overview
brenda
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
brenda
additional information
-
CSGlcAT/ChSy-3 quantitative tissue expression analysis by realtime RT-PCR, overview
brenda
additional information
-
RT-PCR expression analysis of CHSY1, CHSY3 and CSGlcA-T from macroscopically normal and pathological specimens, overview. CHSY1 expression is increased by about 7fold in the adjacent normal tissue of the benign tumors compared to the tumor and healthy control tissues. In the tumor specimens, CHSY1 expression is high during the early stages. The CHSY3 gene is expressed equally and at very low levels in the macroscopically normal and tumor specimens. In benign tumors, CSGlcA-T is markedly elevated by about 40fold compared to the adjacent normal and healthy tissues, while in the cancer specimens it is decreased
brenda
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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
-
brenda
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
-
brenda
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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
additional information
malfunction
-
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
-
silencing of CHSY1 decreases sulfated glycosaminoglycan accumulation in nucleus pulposus cells induced by TGF-beta
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
analysis of the craniofacial morphology in chondroitin sulfate N-acetylgalactosaminyltransferase-1 (T1) gene knockout (KO) mice. T1KO mice shows 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. 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
malfunction
-
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
-
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
-
physiological function
-
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
-
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 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
-
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
-
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
-
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
-
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
-
additional information
-
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
-
either of CSS2A, CSS2B, and CSS1/ChSy-1 heterogeneously and homogeneously interact with each other, suggesting that they form a complex of multimers
-
Show AA Sequence and Transmembrane Helices (163 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
?
x * 111000, about, sequence calculation, x * 100000-130000, recombinant His-tagged enzyme, SDS-PAGE
?
-
x * 111000, about, sequence calculation, x * 100000-130000, recombinant His-tagged enzyme, SDS-PAGE
-
?
-
x * 111000, about, sequence calculation, x * 100000-130000, recombinant His-tagged enzyme, SDS-PAGE
-
additional information
-
homology modeling of the N-terminal domain of CSS2 variants, three-dimensional structure of the N-terminal domain of CSS2 variants showing differences in the catalytic sites, overview
additional information
-
homology modeling of the N-terminal domain of CSS2 variants, three-dimensional structure of the N-terminal domain of CSS2 variants showing differences in the catalytic sites, overview
-
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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
additional information
deletion of the ChGn-2 gene significantly reduces LDL retention in the DIT mouse model. Chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell migration. A functional assay of ASMCs prepared from ChGn-2-/- mice displays abrogation of platelet-derived growth factor (PDGF)-mediated migration via reduced PDGF receptor phosphorylation. Evaluation of LDL retention in a diffuse intimal thickening (DIT) model using partial carotid ligation on ChGn-2/LDL receptor double knockout (ChGn-2-/-/LDLr-/-) mice
additional information
-
deletion of the ChGn-2 gene significantly reduces LDL retention in the DIT mouse model. Chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell migration. A functional assay of ASMCs prepared from ChGn-2-/- mice displays abrogation of platelet-derived growth factor (PDGF)-mediated migration via reduced PDGF receptor phosphorylation. Evaluation of LDL retention in a diffuse intimal thickening (DIT) model using partial carotid ligation on ChGn-2/LDL receptor double knockout (ChGn-2-/-/LDLr-/-) mice
additional information
generation of chondroitin sulfate (CS) N-acetylgalactosaminyltransferase-1 (T1) gene knockout (KO) mice, Ehlers-Danlos syndrome (EDS)-like phenotype and phenotypic features, histological analysis, detailed overview. The protein levels of collagen type 1 and Wnt3a are significantly decreased by T1 gene knockdown by T1KD. Downregulation of collagen type 1 and Wnt3a by T1 gene knockdown in vitro and in vivo
additional information
-
deletion of the ChGn-2 gene significantly reduces LDL retention in the DIT mouse model. Chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell migration. A functional assay of ASMCs prepared from ChGn-2-/- mice displays abrogation of platelet-derived growth factor (PDGF)-mediated migration via reduced PDGF receptor phosphorylation. Evaluation of LDL retention in a diffuse intimal thickening (DIT) model using partial carotid ligation on ChGn-2/LDL receptor double knockout (ChGn-2-/-/LDLr-/-) mice
-
additional information
-
gene silencing via shRNA sequences targeting Rattus norvegicus Smad2, Smad3, CHSY1, c-jun and Sp1, the shRNAs are transfected using a lentiviral vector
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
60% activity remaining after 10 h, 40% activity remaining after 70 h
4 - 20
75% activity remaining after 10 h, 60% activity remaining after 70 h
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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
recombinant soluble N-terminally His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
CSGlcAT/ChSy-3 quantitative tissue expression analysis by realtime RT-PCR, overview
-
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 acbD, encoded within the presumed capsule biosynthesis gene cluster, functional recombinant expression of N-terminally His-tagged enzyme in Escherichia coli strain BL21(DE3) as soluble protein
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
individual overexpression of soluble forms of FLAG- and Myc-tagged splice variants CSS2A and CSS2B in COS-7 cells, co-expression with CSS1. Whereas CSS2A facilitates chondroitin sulfate biosynthesis, CSS2B inhibits it. Analysis of transcription levels of CSS2 variants
-
RT-PCR expression analysis of CHSY1, CHSY3 and CSGlcA-T from macroscopically normal and pathological specimens, overview
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
knockdown of c-Jun and Sp1 decreases CHSY1 promoter activity, CHSY1 expression and sulfated glycosaminoglycan accumulation induced by TGF-beta
-
TGF-beta induces up-regulation of CHSY1 in nucleus pulposus cells through MAPK signaling. TGF-beta increases CHSY1 expression and promoter activity in the nucleus pulposus partially through activation of canonical Smad signaling pathway
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
CSGalNAcT-1 plays a critical role in chondroitin sulfate biosynthesis in cartilage
medicine
-
CSGalNAcT-1 plays a critical role in chondroitin sulphate 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
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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
brenda
Kitagawa, H.; Ujikawa, M.; Tsutsumi, K.; Tamura, J.I.; Neumann, K.W.; Ogawa, T.; Sugahara, K.
Characterization of serum beta-glucuronyltransferase involved in chondroitin sulfate biosynthesis
Glycobiology
7
905-911
1997
Bos taurus
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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)
brenda
Ogawa, H.; Shionyu, M.; Sugiura, N.; Hatano, S.; Nagai, N.; Kubota, Y.; Nishiwaki, K.; Sato, T.; Gotoh, M.; Narimatsu, H.; Shimizu, K.; Kimata, K.; Watanabe, H.
Chondroitin sulfate synthase-2/chondroitin polymerizing factor has two variants with distinct function
J. Biol. Chem.
285
34155-34167
2010
Mus musculus, Mus musculus C57/BL6
brenda
Kalathas, D.; Theocharis, D.A.; Bounias, D.; Kyriakopoulou, D.; Papageorgakopoulou, N.; Stavropoulos, M.S.; Vynios, D.H.
Chondroitin synthases I, II, III and chondroitin sulfate glucuronyltransferase expression in colorectal cancer
Mol. Med. Rep.
4
363-368
2011
Mus musculus
brenda
Ogawa, H.; Hatano, S.; Sugiura, N.; Nagai, N.; Sato, T.; Shimizu, K.; Kimata, K.; Narimatsu, H.; Watanabe, H.
Chondroitin sulfate synthase-2 is necessary for chain extension of chondroitin sulfate but not critical for skeletal development
PLoS ONE
7
e43806
2012
Mus musculus
brenda
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)
brenda
Hu, B.; Shi, C.; Tian, Y.; Zhang, Y.; Xu, C.; Chen, H.; Cao, P.; Yuan, W.
TGF-beta induces up-regulation of chondroitin sulfate synthase 1 (CHSY1) in nucleus pulposus cells through MAPK signaling
Cell. Physiol. Biochem.
37
793-804
2015
Rattus norvegicus
brenda
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
brenda
Wang, T.T.; Zhu, C.Y.; Zheng, S.; Meng, C.C.; Wang, T.T.; Meng, D.H.; Li, Y.J.; Zhu, H.M.; Wang, F.S.; Sheng, J.Z.
Identification and characterization of a chondroitin synthase from Avibacterium paragallinarum
Appl. Microbiol. Biotechnol.
102
4785-4797
2018
Avibacterium paragallinarum (D0QYM5), Avibacterium paragallinarum, Avibacterium paragallinarum ATCC 29545 (D0QYM5), Avibacterium paragallinarum NCTC 11296 (D0QYM5)
brenda
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
Mus musculus (Q6IQX7), Mus musculus, Homo sapiens (Q8IZ52), Homo sapiens, Mus musculus C57BL/6J (Q6IQX7)
brenda
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)
brenda
Liao, W.C.; Liao, C.K.; Tseng, T.J.; Ho, Y.J.; Chen, Y.R.; Lin, K.H.; Lai, T.J.; Lan, C.T.; Wei, K.C.; Liu, C.H.
Chondroitin sulfate synthase 1 enhances proliferation of glioblastoma by modulating PDGFRA stability
Oncogenesis
9
9
2020
Homo sapiens (Q86X52), Homo sapiens
brenda
Ida-Yonemochi, H.; Morita, W.; Sugiura, N.; Kawakami, R.; Morioka, Y.; Takeuchi, Y.; Sato, T.; Shibata, S.; Watanabe, H.; Imamura, T.; Igarashi, M.; Ohshima, H.; Takeuchi, K.
Craniofacial abnormality with skeletal dysplasia in mice lacking chondroitin sulfate N-acetylgalactosaminyltransferase-1
Sci. Rep.
8
17134
2018
Mus musculus (Q6ZQ11)
brenda
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