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Information on EC 2.4.1.175 - glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase and Organism(s) Homo sapiens and UniProt Accession Q8TDX6
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EC Tree
2.4.1.175 glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferaseIUBMB Comments
Involved in the biosynthesis of chondroitin sulfate. The human form of this enzyme is a bifunctional glycosyltransferase, which also has the 3-beta-glucuronosyltransferase (EC 2.4.1.226, N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase) activity required for the synthesis of the chondroitin sulfate disaccharide repeats. Similar chondroitin synthase 'co-polymerases' can be found in Pasteurella multocida and Escherichia coli.
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Word Map
- 2.4.1.175
- glycosaminoglycans
- n-acetylgalactosamine
- udp-galnac
-
glcua
-
sulfotransferases
- medicine
-
glucuronyltransferase
- hexasaccharide
- udp-glca
- udp-sugars
-
d-glucuronic
-
chemo-enzymatically
- diagnostics
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
+
=
+
+
[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)-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
=
+
[protein]-3-O-([beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)]n+1-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
chondroitin polymerase, chsy-2, chondroitin synthase-1, csgalnact-2, n-acetylgalactosaminyltransferase ii, chondroitin synthase 1, cs synthase-1, cs glycosyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acetylgalactosaminyltransferase, uridine diphosphoacetylgalactosamine-chondroitin, II
-
-
-
-
chondroitin sulfate synthase-3
chondroitin synthase
chondroitin synthase-2
based on the experimental results chondroitin sulfate synthase-3 is renamed into chondroitin synthase-2
chondroitin synthase-3
based on the experimental results CSGlcA-T renamed into chondroitin synthase-3
CHSY1
CSS3
glucuronyl-N-acetylgalactosaminylproteoglycan beta1,4-N-acetylgalactosaminyltransferase
-
-
-
-
N-acetylgalactosaminyltransferase II
-
-
-
-
UDP-N-acetyl-D-galactosamine:D-glucuronyl-N-acetyl-1,3-beta-D-galactosaminylproteoglycan beta-1,4-N-acetylgalactosaminyltransferase
-
-
-
-
uridine diphosphoacetylgalactosamine-chondroitin acetylgalactosaminyltransferasec II
-
-
-
-
additional information
chondroitin synthase
-
-
-
-
additional information
the enzyme also has N-acetylgalactosaminyltransferase I activity, EC 2.4.1.174
additional information
the enzyme also has N-acetylgalactosaminyltransferase I activity, EC 2.4.1.174
additional information
the enzyme also has N-acetylgalactosaminyltransferase I activity, EC 2.4.1.174
additional information
the enzyme shows no 3-beta-glucuronosyltransferase activity, EC 2.4.1.226
additional information
the human form of this enzyme is a bifunctional glycosyltransferase, which also has the 3-beta-glucuronosyltransferase, EC 2.4.1.226, activity required for the synthesis of the chondroitin sulfate disaccharide repeats. Similar chondroitin synthase co-polymerases can be found in Pasteurella multocida and Escherichia coli.
additional information
the human form of this enzyme is a bifunctional glycosyltransferase, which also has the 3-beta-glucuronosyltransferase, EC 2.4.1.226, activity required for the synthesis of the chondroitin sulfate disaccharide repeats. Similar chondroitin synthase co-polymerases can be found in Pasteurella multocida and Escherichia coli.
additional information
the human form of this enzyme is a bifunctional glycosyltransferase, which also has the 3-beta-glucuronosyltransferase, EC 2.4.1.226, activity required for the synthesis of the chondroitin sulfate disaccharide repeats. Similar chondroitin synthase co-polymerases can be found in Pasteurella multocida and Escherichia coli.
additional information
the enzyme also has the 3-beta-glucuronosyltransferase, EC 2.4.1.226, activity
additional information
the enzyme also has N-acetylgalactosaminyltransferase I activity, EC 2.4.1.174
additional information
the human form of this enzyme is a bifunctional glycosyltransferase, which also has the 3-beta-glucuronosyltransferase, EC 2.4.1.226, activity required for the synthesis of the chondroitin sulfate disaccharide repeats. Similar chondroitin synthase co-polymerases can be found in Pasteurella multocida and Escherichia coli.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexosyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetyl-D-galactosamine:beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase
Involved in the biosynthesis of chondroitin sulfate. The human form of this enzyme is a bifunctional glycosyltransferase, which also has the 3-beta-glucuronosyltransferase (EC 2.4.1.226, N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase) activity required for the synthesis of the chondroitin sulfate disaccharide repeats. Similar chondroitin synthase 'co-polymerases' can be found in Pasteurella multocida and Escherichia coli.
CAS REGISTRY NUMBER
COMMENTARY
96189-40-1
-
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-N-acetyl-alpha-D-galactosamine + (glucuronyl-N-acetyl-1,3-beta-D-galactosamine)3
UDP + N-acetyl-beta-D-galactosaminyl-1,4-glucuronyl-N-acetyl-1,3-beta-D-galactosaminyl-(glucuronyl-N-acetyl-1,3-beta-D-galactosamine)2
-
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + (glucuronyl-N-acetyl-1,3-beta-D-galactosamine)4
UDP + N-acetyl-beta-D-galactosaminyl-1,4-glucuronyl-N-acetyl-1,3-beta-D-galactosaminyl-(glucuronyl-N-acetyl-1,3-beta-D-galactosamine)3
-
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + (glucuronyl-N-acetyl-1,3-beta-D-galactosamine)5
UDP + N-acetyl-beta-D-galactosaminyl-1,4-glucuronyl-N-acetyl-1,3-beta-D-galactosaminyl-(glucuronyl-N-acetyl-1,3-beta-D-galactosamine)4
-
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + (glucuronyl-N-acetyl-1,3-beta-D-galactosamine)6
UDP + N-acetyl-beta-D-galactosaminyl-1,4-glucuronyl-N-acetyl-1,3-beta-D-galactosaminyl-(glucuronyl-N-acetyl-1,3-beta-D-galactosamine)5
-
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + (glucuronyl-N-acetyl-1,3-beta-D-galactosamine)7
UDP + N-acetyl-beta-D-galactosaminyl-1,4-glucuronyl-N-acetyl-1,3-beta-D-galactosaminyl-(glucuronyl-N-acetyl-1,3-beta-D-galactosamine)6
-
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin oligosaccharide
UDP-N-acetyl-alpha-D-galactosamine + chondroitin sulfate oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin sulfate oligosaccharide
UDP-N-acetyl-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-D-galactosaminyl chondroitin oligosaccharide
UDP-N-acetyl-D-galactosamine + chondroitin polysaccharide
UDP + N-acetyl-D-galactosaminyl chondroitin polysaccharide
best acceptor substrate
-
?
UDP-N-acetyl-D-galactosamine + chondroitin sulfate oligosaccharide
UDP + N-acetyl-D-galactosaminyl chondroitin sulfate oligosaccharide
-
-
?
alpha-thrombomodulin + UDP-N-acetyl-D-galactosamine + UDP-glucuronic acid
?
-
-
-
?
chondroitin + UDP-glucuronic acid
?
chondroitin is the best substrate
-
-
?
chondroitin sulfate A10 + UDP-GalNAc
?
no activity with UDP-glucuronic acid
-
-
?
chondroitin sulfate A11 + UDP-glucuronic acid
?
no activity with UDP-GalNAc
-
-
?
chondroitin sulfate C10 + UDP-GalNAc
?
no activity with UDP-glucuronic acid
-
-
?
chondroitin sulfate C11 + UDP-glucuronic acid
?
no activity with UDP-GalNAc
-
-
?
GlcUAbeta1-3Galbeta1-O-C2H4NH-benzyloxycarbonyl + UDP-glucuronic acid
?
-
-
-
?
GlcUAbeta1-3Galbeta1-O-C2H4NH-benzyloxycarbonyl + UDP-N-acetyl-D-galactosamine
?
-
-
-
?
GlcUAbeta1-3Galbeta1-O-naphthalenemethanol + UDP-glucuronic acid
?
-
-
-
?
GlcUAbeta1-3Galbeta1-O-naphthalenemethanol + UDP-N-acetyl-D-galactosamine
?
-
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + (glucuronyl-N-acetyl-1,3-beta-D-galactosamine)3
UDP + N-acetyl-beta-D-galactosaminyl-1,4-glucuronyl-N-acetyl-1,3-beta-D-galactosaminyl-(glucuronyl-N-acetyl-1,3-beta-D-galactosamine)2
low activity
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + (glucuronyl-N-acetyl-1,3-beta-D-galactosamine)4
UDP + N-acetyl-beta-D-galactosaminyl-1,4-glucuronyl-N-acetyl-1,3-beta-D-galactosaminyl-(glucuronyl-N-acetyl-1,3-beta-D-galactosamine)3
low activity
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-proteoglycan
UDP + N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-proteoglycan
-
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin oligosaccharide
involved in chondroitin biosynthesis
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + chondroitin sulfate oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin sulfate oligosaccharide
involved in chondroitin sulfate biosynthesis: elongation of growing chondroitin sulfate chain
-
-
?
UDP-N-acetyl-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-D-galactosaminyl chondroitin oligosaccharide
UDP-N-acetyl-D-galactosamine + chondroitin sulfate C
UDP + N-acetyl-D-galactosaminyl chondroitin sulfate C
11% activity compared to chondroitin
-
?
UDP-N-acetyl-alpha-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin oligosaccharide
involved in chondroitin biosynthesis
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin oligosaccharide
involved in chondroitin biosynthesis
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + chondroitin sulfate oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin sulfate oligosaccharide
involved in chondroitin sulfate biosynthesis: elongation of growing chondroitin sulfate chain
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + chondroitin sulfate oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin sulfate oligosaccharide
involved in chondroitin sulfate biosynthesis: elongation of growing chondroitin sulfate chain
-
-
?
UDP-N-acetyl-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-D-galactosaminyl chondroitin oligosaccharide
-
-
?
UDP-N-acetyl-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-D-galactosaminyl chondroitin oligosaccharide
low activity
-
?
UDP-N-acetyl-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-D-galactosaminyl chondroitin oligosaccharide
best acceptor substrate
transfer in beta-1,4-linkage
?
UDP-N-acetyl-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-D-galactosaminyl chondroitin oligosaccharide
acceptors are even-numbered chondroitin oligosaccharides with terminal glucuronyl-N-acetyl-1,3-beta-D-galactosamine sequence at non-reducing end, transfers N-acetyl-galactosamine to non-reducing glucuronic acid residues in beta-glycosidic linkage
-
?
UDP-N-acetyl-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-D-galactosaminyl chondroitin oligosaccharide
-
-
?
UDP-N-acetyl-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-D-galactosaminyl chondroitin oligosaccharide
best acceptor substrate
transfer in beta-1,4-linkage
?
additional information
?
-
low activity with sulfated oligosaccharide substrates
-
-
?
additional information
?
-
the enzyme shows no 3-beta-glucuronosyltransferase activity, EC 2.4.1.226
-
-
?
additional information
?
-
the enzyme shows no 3-beta-glucuronosyltransferase activity, EC 2.4.1.226
-
-
?
additional information
?
-
the enzyme also has N-acetylgalactosaminyltransferase I activity, EC 2.4.1.174
-
-
?
additional information
?
-
the enzyme also has N-acetylgalactosaminyltransferase I activity, EC 2.4.1.174
-
-
?
additional information
?
-
the enzyme also has N-acetylgalactosaminyltransferase I activity, EC 2.4.1.174
-
-
?
additional information
?
-
chondroitin sulfates A, C, D, and E, and dermatan sulfate are poor acceptor substrates
-
-
?
additional information
?
-
the enzyme also has N-acetylgalactosaminyltransferase I activity, EC 2.4.1.174
-
-
?
additional information
?
-
the enzyme also has N-acetylgalactosaminyltransferase I activity, EC 2.4.1.174
-
-
?
additional information
?
-
the enzyme also has the 3-beta-glucuronosyltransferase, EC 2.4.1.226, activity
-
-
?
additional information
?
-
chondroitin sulfate A and D are very poor acceptor substrates
-
-
?
additional information
?
-
CSS3 is a glycosyltransferase having both glucuronyltransferase and N-acetylgalactosaminyltransferase activities. It may make a contribution to CS biosynthesis that differs from that of CSS1
-
-
?
additional information
?
-
enzyme exhibits the glucuronyltransferase-II (GlcAT-II) and N-acetylgalactosaminyltransferase-II (GalNAcT-II) activities responsible for the biosynthesis of repeating disaccharide units of chondroitin sulfate. Chondroitin polymerizing factor (ChPF) is required for chondroitin polymerizing activity
-
-
?
additional information
?
-
glucuronyltransferase and N-acetylgalactosaminyltransferase activities are observed when chondroitin, chondroitin sulfate polymer, and their corresponding oligosaccharides are used as the acceptor substrates, reaction products were shown to have a GlcAbeta(13)GalNAc linkage and a GalNAbeta(14)GlcA linkage in the nonreducing terminus of chondroitin
-
-
?
additional information
?
-
possess N-acetylgalactosaminyltransferase-II and glucuronyltransferase-II activities responsible for the elongation of chondroitin sulfate chains but cannot polymerize chondroitin chains by themselves
-
-
?
additional information
?
-
experimental data suggest that enzyme acts as a chondroitin polymerase through its interaction with other ChSy family members in the Golgi apparatus
-
-
?
additional information
?
-
-
experimental data suggest that enzyme acts as a chondroitin polymerase through its interaction with other ChSy family members in the Golgi apparatus
-
-
?
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
?
-
-
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-N-acetyl-alpha-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin oligosaccharide
UDP-N-acetyl-alpha-D-galactosamine + chondroitin sulfate oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin sulfate oligosaccharide
UDP-N-acetyl-alpha-D-galactosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-proteoglycan
UDP + N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-proteoglycan
-
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin oligosaccharide
involved in chondroitin biosynthesis
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + chondroitin sulfate oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin sulfate oligosaccharide
involved in chondroitin sulfate biosynthesis: elongation of growing chondroitin sulfate chain
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin oligosaccharide
involved in chondroitin biosynthesis
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + chondroitin oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin oligosaccharide
involved in chondroitin biosynthesis
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + chondroitin sulfate oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin sulfate oligosaccharide
involved in chondroitin sulfate biosynthesis: elongation of growing chondroitin sulfate chain
-
-
?
UDP-N-acetyl-alpha-D-galactosamine + chondroitin sulfate oligosaccharide
UDP + N-acetyl-beta-D-galactosaminyl chondroitin sulfate oligosaccharide
involved in chondroitin sulfate biosynthesis: elongation of growing chondroitin sulfate chain
-
-
?
additional information
?
-
CSS3 is a glycosyltransferase having both glucuronyltransferase and N-acetylgalactosaminyltransferase activities. It may make a contribution to CS biosynthesis that differs from that of CSS1
-
-
?
additional information
?
-
enzyme exhibits the glucuronyltransferase-II (GlcAT-II) and N-acetylgalactosaminyltransferase-II (GalNAcT-II) activities responsible for the biosynthesis of repeating disaccharide units of chondroitin sulfate. Chondroitin polymerizing factor (ChPF) is required for chondroitin polymerizing activity
-
-
?
additional information
?
-
possess N-acetylgalactosaminyltransferase-II and glucuronyltransferase-II activities responsible for the elongation of chondroitin sulfate chains but cannot polymerize chondroitin chains by themselves
-
-
?
additional information
?
-
experimental data suggest that enzyme acts as a chondroitin polymerase through its interaction with other ChSy family members in the Golgi apparatus
-
-
?
additional information
?
-
-
experimental data suggest that enzyme acts as a chondroitin polymerase through its interaction with other ChSy family members in the Golgi apparatus
-
-
?
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
?
-
-
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
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mn2+
Co2+
divalent cation is essential, Co2+ evokes the highest level of activity
Mn2+
Mn2+
31% as effective as Co2 in reaction with chondroitin sulfate C11 and UDP-glucuronic acid, 64% as effective as Co2+ in reaction with chondroitin sulfate C10 and UDP-GalNAc
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
chondroitin polymerizing factor (ChPF) is required for chondroitin polymerizing activity of mammalian ChSy. Chondroitin polymerization is not demonstrated in vitro using the recombinant enzyme
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5
5.8
Mes buffer, reaction with chondroitin sulfate C11 and UDP-glucuronic acid
6.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
chondroitin N-acetylgalactosaminyltransferase I, not N-acetylgalactosaminyltransferase I EC 2.4.1.174
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
CHSY1 is frequently upregulated in glioblastoma and correlates with high tumor grade and poor survival
additional information
soft tissue sarcomas with myxoid substance: myxoid liposarcoma, 14 of myxofibrosarcoma, 12 of malignant peripheral nerve sheath tumor, and 2 of low-grade fibromyxoid sarcoma. Soft tissue sarcoma is a malignant tumor of nonepithelial extraskeletal origin classified by specific, differentiated cell types
soft tissue sarcomas. Soft tissue sarcoma is a malignant tumor of nonepithelial extraskeletal origin classified by specific, differentiated cell types
additional information
enzyme 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, mmunohistochemic analysis, 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. Immunohistochemical analysis of CHSY1 in soft tissue sarcomas with myxoid substance
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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
-
knockdown of chondroitin expression results in the inhibition of fibroblast proliferation, adhesion and migration, as well as an increasing the number of cells that were arrested in the G2/M phase
malfunction
missense mutations in the ChGn-1 gene results in an altered amount of chondroitin sulfate proteoglycans
malfunction
two missense mutations occur in the CHSY1 gene in patients with neuropathy. These mutations are associated with a profound decrease in enzyme activity. The chondroitin synthase-1 F362S mutation in a patient with neuropathy results in a decrease in chondroitin polymerization activity and the mutant protein is defective in regulating the number of chondroitin sulfate chains via CHSY1. The progression of peripheral neuropathies may result from defects in these regulatory systems
malfunction
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. We explore the changes of cell surface CS and its contribution to malignant growth of glioma cells, by manipulating CS Synthase 1 (CHSY1) expression. Overexpression of CHSY1 inhibits PDGF-triggered decrease in PDGFRA levels, whereas CHSY1 knockdown accelerates PDGFRA decrease following PDGF stimulation. PDGFRA is highly expressed on the cell membrane of CHSY1-overexpressing GL261 tumor tissue sections. PDGFRA inhibition reverses CHSY1-mediated tumor growth in vitro and in vivo
physiological function
ChGn-1 is a key enzyme for production of chondroitin sulfate proteoglycans
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 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). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
95000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
2 potential N-glycosylation sites, either one or both of which are used in COS-1 cells during expression of the recombinant fusion protein
glycoprotein
2 potential N-glycosylation sites, either one or both of which are used in COS-1 cells during expression of the recombinant fusion protein
glycoprotein
2 potential N-glycosylation sites, either one or both of which are used in COS-1 cells during expression of the recombinant fusion protein
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F362S
naturally occuring missense mutation of the CHSY1 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
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
-
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
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA sequence determination and analysis, expression of a truncated form, consisting of the putative catalytic domain, in Spodoptera frugiperda Sf21 insect cells as a soluble FLAG-tagged protein
DNA sequence determination, genomic organization and chromosome localization, functional expression as soluble protein fused to protein A IgG-binding domain in COS-1 cells, secretion into the medium
DNA sequence determination, genomic organization and chromosome localization, functional expression as soluble protein fused to protein A IgG-binding domain in COS-1 cells, secretion into the medium
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, quantitative reverse-transcription PCR enzyme expression analysis
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
genomic organization and chromosome localization, functional expression as soluble protein fused to protein A IgG-binding domain in COS-1 cells, secretion into the medium
soluble form of the enzyme lacking the first 129 amino acids expressed as protein A fusion protein in COS-1 cells
soluble form of the enzyme lacking the first 57 amino acids expressed as protein A fusion protein in COS-1 cells
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance. High expression of CHSY1 is significantly associated with poorer patient outcomes
medicine
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
Gotoh, M.; Sato, T.; Akashima, T.; Iwasaki, H.; Kameyama, A.; Mochizuki, H.; Yada, T.; Inaba, N.; Zhang, Y.; Kikuchi, N.; Kwon, Y.D.; Togayachi, A.; Kudo, T.; Nishihara, S.; Watanabe, H.; Kimata, K.; Narimatsu, H.
Enzymatic synthesis of chondroitin with a novel chondroitin sulfate N-acetylgalactosaminyltransferase that transfers N-acetylgalactosamine to glucuronic acid in initiation and elongation of chondroitin sulfate synthesis
J. Biol. Chem.
277
38189-38196
2002
Homo sapiens (Q8TDX6)
Uyama, T.; Kitagawa, H.; Tamura, J.I.; Sugahara, K.
Molecular cloning and expression of human chondroitin N-acetylgalactosaminyltransferase. The key enzyme for chain initiation and elongation of chondroitin/dermatan sulfate on the protein linkage region tetrasaccharide shared by heparin/heparan sulfate
J. Biol. Chem.
277
8841-8846
2002
Homo sapiens (Q8TDX6)
Uyama, T.; Kitagawa, H.; Tanaka, J.; Tamura, J.i.; Ogawa, T.; Sugahara, K.
Molecular cloning and expression of a second chondroitin N-acetylgalactosaminyltransferase involved in the initiation and elongation of chondroitin/dermatan sulfate
J. Biol. Chem.
278
3072-3078
2003
Homo sapiens (Q8N6G5), Homo sapiens (Q8TDX6)
Kitagawa, H.; Uyama, T.; Sugahara, K.
Molecular cloning and expression of a human chondroitin synthase
J. Biol. Chem.
276
38721-38726
2001
Homo sapiens (Q86X52)
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)
Yada, T.; Sato, T.; Kaseyama, H.; Gotoh, M.; Iwasaki, H.; Kikuchi, N.; Kwon, Y.D.; Togayachi, A.; Kudo, T.; Watanabe, H.; Narimatsu, H.; Kimata, K.
Chondroitin sulfate synthase-3. Molecular cloning and characterization
J. Biol. Chem.
278
39711-39725
2003
Homo sapiens (Q70JA7)
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 (A2V663)
Izumikawa, T.; Koike, T.; Shiozawa, S.; Sugahara, K.; Tamura, J.; Kitagawa, H.
Identification of chondroitin sulfate glucuronyltransferase as chondroitin synthase-3 involved in chondroitin polymerization: chondroitin polymerization is achieved by multiple enzyme complexes consisting of chondroitin synthase family members
J. Biol. Chem.
283
11396-11406
2008
Homo sapiens (Q70JA7), Homo sapiens
Zou, X.H.; Jiang, Y.Z.; Zhang, G.R.; Jin, H.M.; Nguyen, T.M.; Ouyang, H.W.
Specific interactions between human fibroblasts and particular chondroitin sulfate molecules for wound healing
Acta Biomater.
5
1588-1595
2009
Homo sapiens
Tew, S.R.; Pothacharoen, P.; Katopodi, T.; Hardingham, T.E.
SOX9 transduction increases chondroitin sulfate synthesis in cultured human articular chondrocytes without altering glycosyltransferase and sulfotransferase transcription
Biochem. J.
414
231-236
2008
Homo sapiens
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), Homo sapiens
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)
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)
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), Mus musculus (Q6IQX7), 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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