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Information on EC 2.4.1.174 - glucuronylgalactosylproteoglycan 4-beta-N-acetylgalactosaminyltransferase and Organism(s) Mus musculus and UniProt Accession Q8BJQ9
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2.4.1.174 glucuronylgalactosylproteoglycan 4-beta-N-acetylgalactosaminyltransferaseIUBMB Comments
Requires Mn2+. Involved in the biosynthesis of chondroitin sulfate. Key enzyme activity for the initiation of chondroitin and dermatan sulfates, transferring GalNAc to the GlcA-Gal-Gal-Xyl-Ser core.
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The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
csgalnact1, csgalnact2, chondroitin sulfate n-acetylgalactosaminyltransferase 1, galnact-ii, chondroitin n-acetylgalactosaminyltransferase-1, chondroitin sulfate n-acetylgalactosaminyltransferase 2, n-acetylgalactosaminet-ii, galnact-i, chondroitin beta1,4-n-acetylgalactosaminyltransferase-1, chondroitin n-acetylgalactosaminyltransferase-2, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acetylgalactosaminyltransferase, uridine diphosphoacetylgalactosamine-chondroitin, I
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glucuronylgalactosylproteoglycan beta-1,4-N-acetylgalactosaminyltransferase
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N-acetylgalactosaminyltransferase I
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uridine diphosphoacetylgalactosamine-chondroitin acetylgalactosaminyltransferase I
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
UDP-N-acetyl-alpha-D-galactosamine + [protein]-3-O-(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-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine
the enzyme mainly regulates CS synthesis in cartilage
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexosyl group transfer
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetyl-D-galactosamine:D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase
Requires Mn2+. Involved in the biosynthesis of chondroitin sulfate. Key enzyme activity for the initiation of chondroitin and dermatan sulfates, transferring GalNAc to the GlcA-Gal-Gal-Xyl-Ser core.
CAS REGISTRY NUMBER
COMMENTARY
96189-39-8
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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
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosylproteoglycan
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UDP-N-acetyl-D-galactosamine + GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl(2-O-phosphate)
UDP + N-acetyl-D-galactosaminyl-1-4beta-D-GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl(2-O-phosphate)
a phosphorylated tetrasaccharide linkage structure in ChGn-1-/- growth plate cartilage but not in ChGn-2-/- or wild-type growth plate cartilage, preferred substrate of ChGn-1
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UDP-N-acetyl-D-galactosamine + GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl(2-O-phosphate)-1-O-thrombomodulin
UDP + N-acetyl-D-galactosaminyl-1-4beta-D-GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl(2-O-phosphate)-1-O-thrombomodulin
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?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosylproteoglycan
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?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
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?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
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?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
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?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
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?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
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?
additional information
?
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in vitro chondroitin polymerization does not occur on the non-reducing terminal GalNAc-linkage pentasaccharide structure
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?
additional information
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no activity with GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl(2-O-phosphate)-1-O-thrombomodulin and GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl(2-O-phosphate)
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?
additional information
?
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no activity with GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl(2-O-phosphate)-1-O-thrombomodulin and GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl(2-O-phosphate)
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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
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosylproteoglycan
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?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosylproteoglycan
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?
additional information
?
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in vitro chondroitin polymerization does not occur on the non-reducing terminal GalNAc-linkage pentasaccharide structure
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?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
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?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
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?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
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?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
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?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan
UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mn2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
heparan sulfate-synthesis enzymes inhibits chondroitin sulfate as extracellular inhibitor of axon growth
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.8
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
quantitative gene expression and in situ hybridization of genes associated with endochondral ossification
quantitative gene expression and in situ hybridization of genes associated with endochondral ossification
additional information
knee, quantitative RT-PCR enzyme expression analysis of CSGALNACT1
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quantitative analysis of Csgalnact1 and Csgalnact2 transcripts in brain of wild-type and Csgalnact1-/- mice by real-time PCR, overview
knee, quantitative RT-PCR enzyme expression analysis of CSGALNACT2
additional information
isozymes CSGALNACT1 (T1) and CSGALNACT2 (T2) are expressed in different organs
additional information
isozymes CSGALNACT1 (T1) and CSGALNACT2 (T2) are expressed in different organs
additional information
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the enzyme is expressed (at very high levels) in the prehypertrophic zone of the growth plate at E16.5, colocalized with aggrecan core protein. In ATDC5 cells the expression of CSGlcAT and CSGalNAcT-1 correlate well with that of aggrecan core protein. Real time RT-PCR show a high level of chondroitin sulfate N-acetylgalactosaminyltransferase-1 expression in cartilage at E18.5.
additional information
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CSS1 quantitative tissue expression analysis by realtime RT-PCR, overview
additional information
isozymes CSGALNACT1 (T1) and CSGALNACT2 (T2) are expressed in different organs
additional information
isozymes CSGALNACT1 (T1) and CSGALNACT2 (T2) are expressed in different organs
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
metabolism
physiological function
additional information
malfunction
deficiency in chondroitin N-acetylgalactosaminyltransferase-1 reduces the number of chondroitin sulfate chains, leading to skeletal dysplasias in mice. Accumulation of phosphorylated pentasaccharide and tetrasaccharide linkages in ChGn-1-/- growth plate cartilage
malfunction
mice carrying a gene knockout for chondroitin sufate N-acetylgalactosaminyltransferase-1, mutant T1KO, recover more completely from spinal cord injury than wild-type mice and even chondroitinase ABC-treated mice. Synthesis of heparan sulfate, a glycosaminoglycan promoting axonal growth, is also upregulated in TI knockout mice because heparan sulfate-synthesis enzymes are induced in the mutant neurons. Chondroitinase ABC treatment never induces heparan sulfate upregulation. T1KO mice are viable, but they have abnormal bone development and 10% shorter bodies compared to wild-type mice. Reduced chondroitin sulfate levels are associated with reduced scar formation in T1KO mice. Phenotype of enzyme knockout mutant mice, overview
malfunction
abnormalities in perineuronal nets and behavior are observed in mice lacking CSGalNAcT1. Loss of this enzyme reduces the amount of chondroitin sulfate (CS) by approximately 50% in various brain regions. The amount of CS in perineuronal nets (PNNs) is also diminished in T1KO compared to wild-type mice, although the amount of a major CS proteoglycan core protein, aggrecan, is not changed. In T1KO, abnormalities in several behavioral tests, including the open-field test, acoustic startle response, and social preference are observed. Phenotype, overview
malfunction
saturating concentrations of rVAR2 inhibit downstream integrin signaling, which is mimicked by knockdown of the core chondroitin sulfate (CS) synthesis enzymes beta-1,3-glucuronyltransferase 1 (B3GAT1) and chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1). rVAR2 inhibits cellular migration, invasion, and anchorage independent growth in cancer. rVAR2 interacts with chondroitin sulfate glycosaminoglycan (ofCS)-modified proteoglycans
malfunction
t1 single knockout mice (t1 KO) exhibit slight dwarfism and a reduction in chondroitin sulfate (CS) content in cartilage compared with wild-type mice. Impaired chondroitin sulfate (CS) content in cartilage and induction of abnormal endochondral ossification is caused by t1::t2 (CSGALNACT1/CSGALNACT2) double deficiency. DKO mice exhibit postnatal lethality. Col2-DKO mice survive to adulthood and show severe dwarfism compared with t1 KO mice. Histological analysis of epiphyseal cartilage from Col2-DKO mice reveals disrupted endochondral ossification, characterized by drastic GAG reduction in the extracellular matrix. DKO cartilage has reduced chondrocyte proliferation and an increased number of apoptotic chondrocytes compared with wild-type cartilage. Conversely, primary chondrocyte cultures from Col2-DKO knee cartilage have the same proliferation rate as wild-type chondrocytes and low GAG expression levels, indicating that the chondrocytes themselves have an intact proliferative ability. Quantitative RT-PCR analysis of E18.5 cartilage shows that the expression levels of Col2a1 and Ptch1 transcripts tend to decrease in DKO compared with those in wild-type mice. The CS content in DKO cartilage is decreased compared with that in t1 KO cartilage
malfunction
T1KO mice show microscopic abnormalities in the CNS, but are fertile and viable. They have 10% smaller body sizes than wild-type mice due to abnormal skeletal development
metabolism
chondroitin sulfate N-acetylgalactosaminyl-transferase-1 is a key enzyme in chondroitin sulfate biosynthesis
metabolism
CSGalNAcT1 is a key enzyme in chondroitin sulfate synthesis. Chondroitin sulfate (CS) is an important glycosaminoglycan and is mainly found in the extracellular matrix as CS proteoglycans. In the brain, CS proteoglycans are highly concentrated in perineuronal nets (PNNs), which surround synapses and modulate their functions
metabolism
six glycosyltransferases are known to coordinately synthesize the backbone structure of chondroitin sulfate (CS). Two glycosyltransferases, Csgalnact1 (t1) and Csgalnact2 (t2), are critical for initiation of CS synthesis in vitro. According to an in vitro enzymatic characterization, among the six CS glycosyltransferases, only t1 and t2 possessed the ability to independently initiate CS synthesis. t1 efficiently transfers GalNAc onto the linkage tetrasaccharide in vitro, which is common to both CS and heparin sulfate/heparin, and t1 initiation activity is stronger than that of t2
metabolism
the first step (GalNAc transfer) of chondroitin sulfate (CS) backbone synthesis is performed by at least two isoforms, CSGALNACT1 (T1) and CSGALNACT2 (T2), which are expressed in different organs, CS metabolism, roles of CS and perineuronal nets (PNNs) in brain function from the perspective of CS synthesis, overview
physiological function
chondroitin N-acetylgalactosaminyltransferase-1 regulates the number of chondroitin sulfate chains for normal cartilage development. ChGn-1-mediated addition of N-acetylgalactosamine is accompanied by rapid 2-phosphoxylose phosphatase XYLP-dependent dephosphorylation during formation of the CS linkage region. ChGn-1 and XYLP cooperatively regulate the number of chondroitin sulfate chains in growth plate cartilage
physiological function
both chondroitin sulfate N-acetylgalactosaminyltransferase 1 (t1) and chondroitin sulfate N-acetylgalactosaminyltransferase 2 (t2) are necessary for chondroitin sulfate (CS) synthesis and normal chondrocyte differentiation but are not sufficient for all CS synthesis in cartilage. CS biosynthesis is initiated by the transfer of GalNAc residues to the linkage region, which consists of tetrasaccharide units of GlcUA-beta1,3-galactose (Gal)-beta1,3-Gal-beta1,4-xylose (Xyl) attached to the serine residues of the core proteins. This triggers CS elongation by alternating addition of GalNAc and GlcUA residues, which is catalyzed by six glycosyltransferases in mammals. Enzyme t1 and t2 are known to function in both initiation and elongation activity. t1 exhibits stronger initiation activity than t2, indicating that t1 has a vital role in CS synthesis initiation
physiological function
enzyme CSGalNAcT1 is important for plasticity, probably due to regulation of CS-dependent perineuronal nets (PNNs). It plays an important role in supplying CS for PNN development and brain functions related to several characteristic behaviors
physiological function
enzymes beta-1,3-glucuronyltransferase 1 (B3GAT1) and chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1) are key players in the core chondroitin sulfate (CS) synthesis. Oncofetal chondroitin sulfate glycosaminoglycans (ofCSs) are key players in integrin signaling and tumor cell motility, overview
malfunction
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chondroitin sulfate production is reduced by approximately half in CSGalNAcT1-null mice, and the amount of short-chain CS is also reduced compared to wild-type mice. CSGalNAcT1-null mice have reduced skeletal growth, thickness of the growth plate is reduced, and the cartilage of the null mice is significantly smaller than that of wild-type mice, phenotype, overview
malfunction
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Chsy1-/- mice show a profound limb patterning defect in which orthogonally shifted ectopic joints form in the distal digits. Associated with the digit-patterning defect is a shift in cell orientation and an imbalance in chondroitin sulfation. Chondrogenesis is impaired as early as E13.5 in Chsy1-/- embryos. Ectopic, split digit phenotype, overview
malfunction
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CSS2 knockout chondrocyte culture systems, together with siRNA of CSS1, reveal the presence of two CS chain species in length, suggesting two steps of CS chain polymerization; i.e., elongation from the linkage region up to Mr of about 10000 and further extension
malfunction
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deficiency in chondroitin N-acetylgalactosaminyltransferase-1 reduces the numbers of chondroitin sulfate chains, leading to skeletal dysplasias in mice. Knockdown of ChGn-1 decreases chondroitin sulfate levels in L cells, chondroitin sulfate chain lengths in L-shRNAChGn-1-1, L-shRNA ChGn-1-2, and mock-transfected murine L cells, overview
malfunction
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the growth plate of Csgalnact1-/- mice contains shorter and slightly disorganized chondrocyte columns with a reduced volume of the extracellular matrix principally in the proliferative layer. Immunohistochemical analysis reveals that the level of both aggrecan and link protein 1 are decreased in Csgalnact1-/- cartilage with an increase in processed forms of aggrecan core protein, phenotype, overview
malfunction
impaired chndroitin sulfate (CS) content in cartilage and induction of abnormal endochondral ossification is caused by t1::t2 (CSGALNACT1/CSGALNACT2) double deficiency. DKO mice exhibit postnatal lethality, whereas t2 KO mice show normal size and skeletal development. Col2-DKO mice survive to adulthood and show severe dwarfism. Histological analysis of epiphyseal cartilage from Col2-DKO mice reveals disrupted endochondral ossification, characterized by drastic GAG reduction in the extracellular matrix. DKO cartilage has reduced chondrocyte proliferation and an increased number of apoptotic chondrocytes compared with wild-type cartilage. Conversely, primary chondrocyte cultures from Col2-DKO knee cartilage have the same proliferation rate as wild-type chondrocytes and low GAG expression levels, indicating that the chondrocytes themselves have an intact proliferative ability. Quantitative RT-PCR analysis of E18.5 cartilage shows that the expression levels of Col2a1 and Ptch1 transcripts tend to decrease in DKO compared with those in wild-type mice. Phenotype of t2 null mice, overview
metabolism
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chondroitin sulfate biosynthetic pathway and relevant glycosyltransferases, overview
metabolism
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CSS1 and CSS2 differently contribute to chondroitin sulfate biosynthesis, mechanism of chondroitin sulfate biosynthesis, overview. CSS1 participates in both the chondroitin sulfate chain initiation and polymerization, and CSS2 participates in the polymerization, especially in further extension
metabolism
six glycosyltransferases are known to coordinately synthesize the backbone structure of chondroitin sulfate (CS). Two glycosyltransferases, Csgalnact1 (t1) and Csgalnact2 (t2), are critical for initiation of CS synthesis in vitro. According to an in vitro enzymatic characterization, among the six CS glycosyltransferases, only t1 and t2 possessed the ability to independently initiate CS synthesis. t1 efficiently transfers GalNAc onto the linkage tetrasaccharide in vitro, which is common to both CS and heparin sulfate/heparin, and t1 initiation activity is stronger than that of t2
metabolism
the first step (GalNAc transfer) of chondroitin sulfate (CS) backbone synthesis is performed by at least two isoforms, CSGALNACT1 (T1) and CSGALNACT2 (T2), which are expressed in different organs, CS metabolism, roles of CS and perineuronal nets (PNNs) in brain function from the perspective of CS synthesis, overview
physiological function
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ChGn-1 initiates chondroitin sulfate biosynthesis by transferring the first N-acetylgalactosamine to the tetrasaccharide in the protein linkage region of chondroitin sulfate, overview. c-2 efficiently transfers sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 4 of non-reducing terminal GalNAc-linkage residues, and the number of chondroitin chains is regulated by the expression levels of C4ST-2 and of ChGn-1. C4ST-2 plays a key role in regulating levels of chondroitin sulfate synthesized via ChGn-1, overview
physiological function
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chondroitin sulfate N-acetylgalactosaminyltransferase 1, CSGalNAcT-1, participates in the chondroitin sulfate chain initiation and is necessary for normal endochondral ossification and aggrecan metabolism
physiological function
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chondroitin sulfate N-acetylgalactosaminyltransferase-1 is required for normal cartilage development
physiological function
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Chsy1 catalyzes the extension of chondroitin and dermatan sulfate glycosaminoglycans and is an essential regulator of joint patterning
physiological function
both chondroitin sulfate N-acetylgalactosaminyltransferase 1 (t1) and chondroitin sulfate N-acetylgalactosaminyltransferase 2 (t2) are necessary for chondroitin sulfate (CS) synthesis and normal chondrocyte differentiation but are not sufficient for all CS synthesis in cartilage. CS biosynthesis is initiated by the transfer of GalNAc residues to the linkage region, which consists of tetrasaccharide units of GlcUA-beta1,3-galactose (Gal)-beta1,3-Gal-beta1,4-xylose (Xyl) attached to the serine residues of the core proteins. This triggers CS elongation by alternating addition of GalNAc and GlcUA residues, which is catalyzed by six glycosyltransferases in mammals. t1 and t2 are known to function in both initiation and elongation activity. Enzyme t1 exhibits stronger initiation activity than t2, indicating that t1 has a vital role in CS synthesis initiation
additional information
proportion of linkage region saccharides from wild-type, ChGn-1-/-, or ChGn-2-/- cartilage, overview
additional information
proportion of linkage region saccharides from wild-type, ChGn-1-/-, or ChGn-2-/- cartilage, overview
additional information
quantitative analysis of six CS glycosyltransferase transcripts using real-time RT-PCR
additional information
quantitative analysis of six CS glycosyltransferase transcripts using real-time RT-PCR
additional information
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the enzyme occurs in a heterooligomer complex, chondroitin sulfate synthase-1 (CSS1)/chondroitin synthase-1
additional information
proportion of linkage region saccharides from wild-type, ChGn-1-/-, or ChGn-2-/- cartilage, overview
additional information
proportion of linkage region saccharides from wild-type, ChGn-1-/-, or ChGn-2-/- cartilage, overview
additional information
quantitative analysis of six CS glycosyltransferase transcripts using real-time RT-PCR
additional information
quantitative analysis of six CS glycosyltransferase transcripts using real-time RT-PCR
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). CGAT1_MOUSE
530
1
60917
Swiss-Prot
Secretory Pathway (Reliability: 1)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
construction of RNAi-mediated gene Csgalnact1 knockout mice, mutant T1KO. T1KO mice are viable, but they have abnormal bone development and 10% shorter bodies compared to wild-type mice. Heparan sulfate synthesis increases in injured spinal cords of T1KO mice
additional information
generation of mice that are deficient in the CS synthesizing enzyme, CSGalNAcT1 (T1KO)
additional information
generation of single knockout T1 KO mutant and of double knockout mutant Col2-DKO, a chondrocyte-specific t1::t2 KO mutant, quantitative RT-PCR analysis of knee cartilage shows no or slight t1 and t2 gene expression in Col2-DKO mice compared with wild-type mice. t1::t2 double KO mice show severe dwarfism and postnatal lethality, pgenotype, overview
additional information
generation of single knockout T1 KO mutant and of double knockout mutant Col2-DKO, a chondrocyte-specific t1::t2 KO mutant, quantitative RT-PCR analysis of knee cartilage shows no or slight t1 and t2 gene expression in Col2-DKO mice compared with wild-type mice. t1::t2 double KO mice show severe dwarfism and postnatal lethality, pgenotype, overview
additional information
saturating concentrations of rVAR2 inhibit downstream integrin signaling, which is mimicked by knockdown of the core CS synthesis enzymes beta-1,3-glucuronyltransferase 1 (B3GAT1) and chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1) via siRNA. The oncofetal chondroitin sulfate glycosaminoglycan chains (ofCS) modification is highly expressed in both human and murine metastatic lesions in situ and pre-incubation or early intravenous treatment of tumor cells with rVAR2-inhibited seeding and spreading of tumor cells in mice
additional information
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saturating concentrations of rVAR2 inhibit downstream integrin signaling, which is mimicked by knockdown of the core CS synthesis enzymes beta-1,3-glucuronyltransferase 1 (B3GAT1) and chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1) via siRNA. The oncofetal chondroitin sulfate glycosaminoglycan chains (ofCS) modification is highly expressed in both human and murine metastatic lesions in situ and pre-incubation or early intravenous treatment of tumor cells with rVAR2-inhibited seeding and spreading of tumor cells in mice
additional information
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in cmd mice (known as natural aggrecan-null mice) the heterozygote and homozygote cartilage exhibit about 50% and about 9% aggrecan gene transcription respectively. In the cmd heterozygote cartilage, chondroitin sulfate N-acetylgalactosaminyltransferase-1 expression is dimnished to about 30% that of the wild type. In the cmd homozygote cartilage, chondroitin sulfate N-acetylgalactosaminyltransferase-1 expression furhter decreases to a low level.
additional information
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construction of CSGalNAcT1-null mice by homologous recombination using an embryonic stem cell line, RENKA, developed from the wild-type C57BL/6N strain
additional information
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construction of L-shRNA ChGn-1-1 and L-shRNA ChGn-1-2 transfected L cells, and analysis of chondroitin sulfate chain lengths. The silencing of the genes results in a 60-80% reduction in steady-state ChGn-1 mRNA and an 18-22% decrease in CS when compared with control L cells. Overexpression of ChGn-1 slightly increases CS levels in L cells
additional information
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generation of Csgalnact1-/- mice by using a targeting vector for Csgalnact1 gene disruption
additional information
generation of single knockout T2 KO mutant and of double knockout mutant Col2-DKO, a chondrocyte-specific t1::t2 KO mutant, quantitative RT-PCR analysis of knee cartilage shows no or slight t1 and t2 gene expression in Col2-DKO mice compared with wild-type mice. t1::t2 double KO mice show severe dwarfism and postnatal lethality, phenotype, overview
additional information
generation of single knockout T2 KO mutant and of double knockout mutant Col2-DKO, a chondrocyte-specific t1::t2 KO mutant, quantitative RT-PCR analysis of knee cartilage shows no or slight t1 and t2 gene expression in Col2-DKO mice compared with wild-type mice. t1::t2 double KO mice show severe dwarfism and postnatal lethality, phenotype, overview
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene CSGALNACT1 or t1, quantitative RT-PCR enzyme expression analysis of CS glycosyltransferases
gene CSGALNACT1, quantitative real-time RT-PCR enzyme expression analysis
gene CSGALNACT2 or t2, quantitative RT-PCR enzyme expression analysis of CS glycosyltransferases
gene CSGALNACT2, quantitative real-time RT-PCR enzyme expression analysis
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
T1 is upregulated in reactive astrocytes after spinal cord injury (SCI)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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
Watanabe, Y.; Takeuchi, K.; Higa Onaga, S.; Sato, M.; Tsujita, M.; Abe, M.; Natsume, R.; Li, M.; Furuichi, T.; Saeki, M.; Izumikawa, T.; Hasegawa, A.; Yokoyama, M.; Ikegawa, S.; Sakimura, K.; Amizuka, N.; Kitagawa, H.; Igarashi, M.
Chondroitin sulfate N-acetylgalactosaminyltransferase-1 is required for normal cartilage development
Biochem. J.
432
47-55
2010
Mus musculus, Mus musculus C57BL/6N
Izumikawa, T.; Koike, T.; Kitagawa, H.
Chondroitin 4-O-sulfotransferase-2 regulates the number of chondroitin sulfate chains initiated by chondroitin N-acetylgalactosaminyltransferase-1
Biochem. J.
441
697-705
2012
Mus musculus
Wilson, D.G.; Phamluong, K.; Lin, W.Y.; Barck, K.; Carano, R.A.; Diehl, L.; Peterson, A.S.; Martin, F.; Solloway, M.J.
Chondroitin sulfate synthase 1 (Chsy1) is required for bone development and digit patterning
Dev. Biol.
363
413-425
2012
Mus musculus
Sato, T.; Kudo, T.; Ikehara, Y.; Ogawa, H.; Hirano, T.; Kiyohara, K.; Hagiwara, K.; Togayachi, A.; Ema, M.; Takahashi, S.; Kimata, K.; Watanabe, H.; Narimatsu, H.
Chondroitin sulfate N-acetylgalactosaminyltransferase 1 is necessary for normal endochondral ossification and aggrecan metabolism
J. Biol. Chem.
286
5803-5812
2011
Mus musculus, Mus musculus C57/BL6J
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
Izumikawa, T.; Sato, B.; Mikami, T.; Tamura, J.; Igarashi, M.; Kitagawa, H.
GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl(2-O-phosphate) is the preferred substrate for chondroitin N-acetylgalactosaminyltransferase-1
J. Biol. Chem.
290
5438-5448
2015
Mus musculus (Q8BJQ9), Mus musculus (Q8C1F4), Mus musculus C57BL/6 (Q8BJQ9), Mus musculus C57BL/6 (Q8C1F4)
Takeuchi, K.; Yoshioka, N.; Higa Onaga, S.; Watanabe, Y.; Miyata, S.; Wada, Y.; Kudo, C.; Okada, M.; Ohko, K.; Oda, K.; Sato, T.; Yokoyama, M.; Matsushita, N.; Nakamura, M.; Okano, H.; Sakimura, K.; Kawano, H.; Kitagawa, H.; Igarashi, M.
Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury
Nat. Commun.
4
2740
2013
Mus musculus (Q8BJQ9)
Yoshioka, N.; Miyata, S.; Tamada, A.; Watanabe, Y.; Kawasaki, A.; Kitagawa, H.; Takao, K.; Miyakawa, T.; Takeuchi, K.; Igarashi, M.
Abnormalities in perineuronal nets and behavior in mice lacking CSGalNAcT1, a key enzyme in chondroitin sulfate synthesis
Mol. Brain
10
47
2017
Mus musculus (Q8BJQ9)
Clausen, T.M.; Pereira, M.A.; Al Nakouzi, N.; Oo, H.Z.; Agerbaek, M.O.; Lee, S.; Oerum-Madsen, M.S.; Kristensen, A.R.; El-Naggar, A.; Grandgenett, P.M.; Grem, J.L.; Hollingsworth, M.A.; Holst, P.J.; Theander, T.; Sorensen, P.H.; Daugaard, M.; Salanti, A.
Oncofetal chondroitin sulfate glycosaminoglycans are key players in integrin signaling and tumor cell motility
Mol. Cancer Res.
14
1288-1299
2016
Homo sapiens (Q8TDX6), Homo sapiens, Mus musculus (Q8BJQ9), Mus musculus, Mus musculus C57BL/6 (Q8BJQ9)
Igarashi, M.; Takeuchi, K.; Sugiyama, S.
Roles of CSGalNAcT1, a key enzyme in regulation of CS synthesis, in neuronal regeneration and plasticity
Neurochem. Int.
119
77-83
2018
Homo sapiens (Q8N6G5), Homo sapiens (Q8TDX6), Mus musculus (Q8BJQ9), Mus musculus (Q8C1F4)
Shimbo, M.; Suzuki, R.; Fuseya, S.; Sato, T.; Kiyohara, K.; Hagiwara, K.; Okada, R.; Wakui, H.; Tsunakawa, Y.; Watanabe, H.; Kimata, K.; Narimatsu, H.; Kudo, T.; Takahashi, S.
Postnatal lethality and chondrodysplasia in mice lacking both chondroitin sulfate N-acetylgalactosaminyltransferase-1 and -2
PLoS ONE
12
e0190333
2017
Mus musculus (Q8BJQ9), Mus musculus (Q8C1F4), Mus musculus C57BL/6 (Q8BJQ9), Mus musculus C57BL/6 (Q8C1F4)
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