Information on EC 2.4.1.224 - glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
2.4.1.224
-
RECOMMENDED NAME
GeneOntology No.
glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan = UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
transfer of alpha-N-acetylglucosamine
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Glycosaminoglycan biosynthesis - heparan sulfate / heparin
-
heparan sulfate biosynthesis (late stages)
-
Metabolic pathways
-
SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetyl-D-glucosamine:beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase
Involved in the biosynthesis of heparin and heparan sulfate. Some forms of the enzyme from human (particularly the enzyme complex encoded by the EXT1 and EXT2 genes) act as bifunctional glycosyltransferases, which also have the 4-beta-glucuronosyltransferase (EC 2.4.1.225, N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase) activity required for the synthesis of the heparan sulfate disaccharide repeats. Other human forms of this enzyme (e.g. the product of the EXTL1 gene) have only the 4-alpha-N-acetylglucosaminyltransferase activity. In Caenorhabditis elegans, the product of the rib-2 gene displays the activities of this enzyme as well as EC 2.4.1.223, glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
alpha-N-acetylglucosaminyltransferase II
-
-
-
-
exostosin-1
-
-
Exostosin1
-
-
Exostosin1
Mus musculus BALB/c
-
-
-
Exostosin2
-
-
Exostosin2
Mus musculus BALB/c
-
-
-
EXT1
-
-
EXT1
Q93063
-
EXT1
-
gene name
EXT1
Mus musculus BALB/c
-
gene name
-
EXT2
-
gene name
EXT2
-
-
EXT2
Q16394
-
EXT2
-
-
EXT2
-
gene name
EXT2
Mus musculus BALB/c
-
gene name
-
glucuronyl-N-acetylglucosaminoproteoglycan 4-alpha-N-acetylglucosaminyltransferase
-
-
-
-
heparan sulfate polymerase
-
-
-
-
N-acetyl-D-glucosaminyl-(N-acetyl-D-glucosamine) transferase
-
-
-
-
sister of tout velu
-
-
sister of tout-velu
-
c.f. EC 2.4.1.225
sotv
-
c.f. EC 2.4.1.225
tout-velu
-
c.f. EC 2.4.1.225
ttv
-
c.f. EC 2.4.1.225
UDP-GlcNAc:oligosaccharide beta-N-acetylglucosaminyltransferase
-
-
-
-
additional information
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
145539-84-0
-
336193-98-7
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
enzyme EXT2, enzyme EXT1 from Homo sapiens
-
-
Manually annotated by BRENDA team
EXT2 protein
-
-
Manually annotated by BRENDA team
deficiency mutant CHO-K1 used for experiments
-
-
Manually annotated by BRENDA team
deficiency mutant CHO-K1 used for experiments; mutation in pgsD gene locus
-
-
Manually annotated by BRENDA team
gene ext2
-
-
Manually annotated by BRENDA team
enzyme sotv, homologue of mammalian EXT2
-
-
Manually annotated by BRENDA team
enzymes ttv and sotv
-
-
Manually annotated by BRENDA team
Escherichia coli O18:K5
K 5
-
-
Manually annotated by BRENDA team
enzyme EXT1, EXT2 constructs from Bos taurus
-
-
Manually annotated by BRENDA team
enzymes EXT1 and EXT2
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-
Manually annotated by BRENDA team
recombinant enzymes EXT1 and EXT2 lacking transmembrane domains
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-
Manually annotated by BRENDA team
adult 6-week-old C57BL/6 mice
-
-
Manually annotated by BRENDA team
EXT1 protein
-
-
Manually annotated by BRENDA team
gene sext1 and ext2
-
-
Manually annotated by BRENDA team
wild type mouse fibroblasts and deficiency mutant cell line gro2C
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-
Manually annotated by BRENDA team
wild type mouse fibroblasts and deficiency mutant cell line Sog9, EXT1 protein
-
-
Manually annotated by BRENDA team
Mus musculus BALB/c
gene sext1 and ext2
-
-
Manually annotated by BRENDA team
no activity in yeast
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
EXT1 influences fibroblast matrix interactions. Essential role of EXT1 in providing specific binding sites for growth factors and extracellular matrix proteins. Phosphorylation of ERK1/2 in response to FGF2 stimulation is markedly decreased in the Ext1 mutant fibroblasts, whereas neither PDGF-BB nor FGF10 signaling is significantly affected. Ext1 mutants display reduced ability to attach to collagen I and to contract collagen lattices. Reintroduction of Ext1 in Ext1 mutant fibroblasts rescues heparan sulfate chain length, FGF2 signaling, and the ability of the fibroblasts to contract collagen
malfunction
-
Fgf targeted gene expression is reduced in ext2 mutants and the remaining expression is readily inhibited by SU5402, an FGF receptor inhibitor. In the ext2 mutants, Fgf signaling is affected during nervous system development, mechanism, overview, and reduction of Fgf ligands in the mutants affects tail development. Wnt signaling is also affected in the ext2 mutants, while Hh dependent signaling is apparently unaffected in the ext2 mutants, Hh targeted gene expression is not reduced, the Hh inhibitor cyclopamine is not more affective in the mutants and Hh-dependent cell differentiation in the retina and in the myotome are normal in ext2 mutants, ext2 mutant phenotypes, overview
malfunction
-
conditional Ext1 mutant mice display severe limb skeletal defects, including shortened and malformed limb bones, oligodactyly, and fusion of joints. the segregation of the pSmad1/5/8-expressing chondrocytes and fibronectin-expressing perichondrium-like cells surrounding chondrocyte nodules is disrupted in mutant micromass cultures, Ext2-mutant phenotypes, detailed overview
malfunction
-
a reduction in either Ext1 or Ext2 can cause a reduction in heparan sulfate biosynthesis, overview. Suppression of Ext1 by siRNA in FBJ-S1 cells results in the decreased expression of heparan sulfate and enhanced motility
malfunction
Mus musculus BALB/c
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a reduction in either Ext1 or Ext2 can cause a reduction in heparan sulfate biosynthesis, overview. Suppression of Ext1 by siRNA in FBJ-S1 cells results in the decreased expression of heparan sulfate and enhanced motility
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physiological function
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in patients with hereditary multiple exostoses, functional loss of EXT1 results in exostoses (osteochondromas), but inactivation of both copies of the gene (germline mutation plus loss of the remaining wild-type allele) is not required for development of the bone lesions. No reported association between EXT1 abnormalities and renal disease. Deficiency of heparan sulfate and perlecan, together with accumulation of collagens, in the matrix of EXT1-associated osteochondromas
physiological function
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Ext1 and Ext2 together form a copolymerase which is responsible for the polymerization process where repeating units of N-acetylglucosamine and glucuronic acid are incorporated in the growing linear polysaccharide chain, see also EC 2.4.1.225. Gene ext2 is involved in Fgf and Wnt signaling but not in Hh signaling, ext2 is a general enhancer of Fgf target gene expression, ext2 interacts genetically with Fgf signaling during tail development, specificity for gene ext2 in signaling pathways during embryonic development, overview
physiological function
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Ext1 encodes an essential glycosyltransferase for heparan sulfate synthesis, heparan sulfate is essential for patterning of limb skeletal elements
physiological function
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Ext1 and Ext2 are tumor suppressors. In the biosynthesis of heparan sulfate, after the attachment of a GlcNAc residue to GlcA-Gal-Gal-Xyl, Ext1 and Ext2 catalyze the subsequent elongation of glycosaminoglycans by alternately adding GlcA and GlcNAc to the end of the growing chain. Involvement of Ext1 and heparanase in migration of FBJ osteosarcoma cells, overview
physiological function
Mus musculus BALB/c
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Ext1 and Ext2 are tumor suppressors. In the biosynthesis of heparan sulfate, after the attachment of a GlcNAc residue to GlcA-Gal-Gal-Xyl, Ext1 and Ext2 catalyze the subsequent elongation of glycosaminoglycans by alternately adding GlcA and GlcNAc to the end of the growing chain. Involvement of Ext1 and heparanase in migration of FBJ osteosarcoma cells, overview
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SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
UDP-N-acetyl-D-glucosamine + alpha-D-glucuronosyl-(1-4)-N-acetylglucoside
UDP + alpha-N-acetyl-D-glucosaminyl-alpha-D-glucuronosyl-(1-4)-N-acetylglucoside
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1,4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1,4)-beta-D-glucuronosyl-(1,4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
O77783
-
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
Q9XZ08
-
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
O77783
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
Q9XZ08
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
Escherichia coli K5
-
-, elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
Escherichia coli O18:K5
-
-, elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + N-acetylheparosan oligosaccharide
?
show the reaction diagram
Q9XZ08
with terminal nonreducing glucuronic acid
-
-
?
UDP-N-acetyl-D-glucosamine + [D-glucuronic acid-N-acetyl-D-glucoseamin]n-D-glucuronic acid-2,5-anhydro-D-mannose
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-N-acetyl-D-glucoseamine-[D-glucuronic acid-N-acetyl-D-glucosamine]n-D-glucuronic acid-2,5-anhydro-D-mannose
show the reaction diagram
-
heptasaccharide and nonasaccharide serve as acceptors
-
-
?
UDP-N-acetyl-D-glucosamine + [D-glucuronic acid-N-acetyl-D-glucoseamin]n-D-glucuronic acid-2,5-anhydro-D-mannose
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-N-acetyl-D-glucoseamine-[D-glucuronic acid-N-acetyl-D-glucosamine]n-D-glucuronic acid-2,5-anhydro-D-mannose
show the reaction diagram
-
octasaccharide but not nonasaccharide serves as acceptor
-
?
UDP-N-acetyl-D-glucosamine + [D-glucuronic acid-N-acetyl-D-glucoseamin]n-D-glucuronic acid-2,5-anhydro-D-mannose
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-N-acetyl-D-glucoseamine-[D-glucuronic acid-N-acetyl-D-glucosamine]n-D-glucuronic acid-2,5-anhydro-D-mannose
show the reaction diagram
-
different activities observed for acetylated and sulfated acceptors
-
-
?
UDP-N-acetyl-D-glucosamine + [D-glucuronic acid-N-acetyl-D-glucoseamin]n-D-glucuronic acid-2,5-anhydro-D-mannose
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-N-acetyl-D-glucoseamine-[D-glucuronic acid-N-acetyl-D-glucosamine]n-D-glucuronic acid-2,5-anhydro-D-mannose
show the reaction diagram
-
substrate is produced by E. coli K5, acceptor ability increases with increasing chain length
-
-
?
UDP-N-acetyl-D-glucosamine + [D-glucuronic acid-N-acetyl-D-glucoseamin]n-D-glucuronic acid-2,5-anhydro-D-mannose
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-N-acetyl-D-glucoseamine-[D-glucuronic acid-N-acetyl-D-glucosamine]n-D-glucuronic acid-2,5-anhydro-D-mannose
show the reaction diagram
Escherichia coli K5
-
heptasaccharide and nonasaccharide serve as acceptors, different activities observed for acetylated and sulfated acceptors
-
-
?
UDP-N-acetyl-D-glucosamine + [D-glucuronic acid-N-acetyl-D-glucoseamin]n-D-glucuronic acid-2,5-anhydro-D-mannose
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-N-acetyl-D-glucoseamine-[D-glucuronic acid-N-acetyl-D-glucosamine]n-D-glucuronic acid-2,5-anhydro-D-mannose
show the reaction diagram
Escherichia coli O18:K5
-
heptasaccharide and nonasaccharide serve as acceptors, different activities observed for acetylated and sulfated acceptors
-
-
?
UDP-N-acetyl-D-glucosamine + [mannose]5-N-acetyl-D-glucosamine
?
show the reaction diagram
-
-
-
?
UDP-N-acetyl-D-glucosamine + [mannose]9-N-acetyl-D-glucosamine
?
show the reaction diagram
-
-
-
?
additional information
?
-
-
EXT1 and EXT2 proteins also acts as beta(1,4)-glucuronyltransferase (EC 2.4.1.225)
-
-
-
additional information
?
-
-
EXT1 and EXT2 proteins also acts as beta(1,4)-glucuronyltransferase (EC 2.4.1.225)
-
-
-
additional information
?
-
-
EXT1 and EXT2 proteins also acts as beta(1,4)-glucuronyltransferase (EC 2.4.1.225)
-
-
-
additional information
?
-
O77783
EXT1 and EXT2 proteins also acts as beta(1,4)-glucuronyltransferase (EC 2.4.1.225)
-
-
-
additional information
?
-
-
EXT1 and EXT2 proteins also acts as beta(1,4)-glucuronyltransferase (EC 2.4.1.225)
-
-
-
additional information
?
-
-
different acceptors tested for activity with UDP-N-acetyl-D-glucosamine
-
-
-
additional information
?
-
-
formation of homo- and heterooligomeric complex of EXT1 and EXT2, heterooligomeric complexes have substantially higher glycosyltransferase activity than EXT1 or EXT2 has alone
-
-
-
additional information
?
-
-
formation of homo- and heterooligomeric complexes of EXT1 and EXT2, heterooligomeric complexes have substantially higher glycosyltransferase activity than EXT1 or EXT2 has alone
-
-
-
additional information
?
-
-
the EXT1 and EXT2 hetero-oligomeric complex has glycosyltransferase activity that is essential for the synthesis and expression of heparan sulfate glycosaminoglycans
-
-
-
additional information
?
-
Mus musculus, Mus musculus BALB/c
-
the Ext1/Ext2 complex possesses higher glycosyltransferase activity than Ext1 or Ext2 alone
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
O77783
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
Q9XZ08
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan
show the reaction diagram
Escherichia coli K5, Escherichia coli O18:K5
-
elongation of growing chains of heparin and heparan sulfate, tumor suppressor
-
-
?
additional information
?
-
Mus musculus, Mus musculus BALB/c
-
the Ext1/Ext2 complex possesses higher glycosyltransferase activity than Ext1 or Ext2 alone
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mn2+
-
required, can not be substituted by other divalent cations
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
Detergent
-
required, range from 0.03-1%
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.094
-
UDP-N-acetyl-D-glucosamine
-
pH 7.2
0.3
-
UDP-N-acetyl-D-glucosamine
-
-
0.4
-
UDP-N-acetyl-D-glucosamine
-
-
1.2
-
UDP-N-acetyl-D-glucosamine
-
-
0.006
-
[D-glucuronic acid-N-acetyl-glucosamine]14 -D-glucuronic acid-2,5-anhydro-D-mannose
-
-
-
0.06
-
[D-glucuronic acid-N-acetyl-glucosamine]4 -D-glucuronic acid-2,5-anhydro-D-mannose
-
-
0.65
-
(mannose)9 -N-acetyl-D-glucosamine
-
-
additional information
-
additional information
-
KM-values for the disaccahride, tetrasaccharide, hexasaccharide and octasaccharide acceptors
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
specific activities of different pgsD mutants tested
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
7.2
-
broad optimum
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.2
8.4
-
-
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
-
-
EXT2, calculated
7.5
-
-
heterodimer EXT1/EXT2, calculated
9
-
-
EXT1, calculated
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
Q16394, Q93063
loss of one copy of either the EXT1 or EXT2 gene product compromises the perichondrial chondrocytes’ ability to differentiate normally and to survive in a differentiated state in vitro; loss of one copy of either the EXT1 or EXT2 gene product compromises the perichondrial chondrocytes’ ability to differentiate normally and to survive in a differentiated state in vitro
Manually annotated by BRENDA team
-
enzyme EXT1
Manually annotated by BRENDA team
-
the mRNA expression of EXT2, one of the crucial enzymes for heparan sulfate-glycosaminoglycan synthesis, is markedly up-regulated in injured hypoglossal motor neurons after axotomy
Manually annotated by BRENDA team
-
FBJ, highly metastatic mouse osteosarcoma FBJ-LL cells and the poorly metastatic FBJ-S1 cells are produced from a FBJ virus-induced osteosarcoma
Manually annotated by BRENDA team
Mus musculus BALB/c
-
FBJ, highly metastatic mouse osteosarcoma FBJ-LL cells and the poorly metastatic FBJ-S1 cells are produced from a FBJ virus-induced osteosarcoma
-
Manually annotated by BRENDA team
additional information
-
zebrafish ext2 gene is ubiquitously expressed during zebrafish development
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
identical localization of sotv and ttv
Manually annotated by BRENDA team
-
EXT1 is an endoplasmic reticulum-localized type II transmembrane glycoprotein
Manually annotated by BRENDA team
-
Ext1 and Ext2 are type II transmembrane glycoproteins
Manually annotated by BRENDA team
Mus musculus BALB/c
-
Ext1 and Ext2 are type II transmembrane glycoproteins
-
Manually annotated by BRENDA team
-
identical localization of sotv and ttv
Manually annotated by BRENDA team
-
transmembrane glycoprotein
Manually annotated by BRENDA team
-
EXT1 and EXT2 form a hetero-oligomeric complex that accumulates in the Golgi apparatus
Manually annotated by BRENDA team
-
transmembrane protein
Manually annotated by BRENDA team
Escherichia coli K5, Escherichia coli O18:K5
-
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
69000
71000
-
SDS-PAGE
70000
-
O77783
SDS-PAGE, purified enzyme; SDS-PAGE, soluble form
80000
-
-
SDS-PAGE of expressed EXT1 and EXT2 proteins, weak band at 90000 D
80000
-
-
EXT2, gel filtration
86300
-
-
EXT1
88000
-
-
SDS-PAGE, species two with second species with MW 91000
90000
-
-
SDS-PAGE of coexpressed EXT1 and EXT2, no second band detected
91000
-
-
SDS-PAGE, species one with second species with MW 88000
110000
-
-
expressed fusion protein from COS-1after N-glycosidase treatment, SDS-PAGE
130000
-
-
expressed fusion protein from COS-1, SDS-PAGE
160000
-
-
EXT1, and coexpressed EXT1/EXT2, gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 27000, SDS-PAGE
dimer
-
2 * 80000, EXT1, calculated, 1 * 80000 + 1 * 80000, EXT1/EXT2 heterodimer, calculated
monomer
-
80000, EXT2, calculated
additional information
-
formation of heterooligomers of ttv and sotv, co-immunoprecipitation experiments
additional information
-
formation of homo- and heterooligomeric complexes of EXT1 and EXT2, heterooligomeric complexes have substantially higher glycosyltransferase activity than EXT1 or EXT2 has alone
additional information
-
formation of homo- and heterooligomeric complex of EXT1 and EXT2, heterooligomeric complexes have substantially higher glycosyltransferase activity than EXT1 or EXT2 has alone
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
glycoprotein
-
N-linked glycosylation, Endo H treatment does not effect 80000 Da species but reduces size of 90000 Da species that is found mainly when both proteins are coexpressed
glycoprotein
-
-
glycoprotein
-
N-linked glycosylation, molecular weight of expressed fusion protein is reduced from 1300000 to 110000 by N-glycosidase treatment
glycoprotein
-
-
glycoprotein
-
N-linked glycosylation, Endo H treatment does not effect 80000 Da species but reduces size of 90000 Da species that is found mainly when both proteins are coexpressed
glycoprotein
-
-
glycoprotein
-
Ext1 and Ext2 are type II transmembrane glycoproteins
glycoprotein
Mus musculus BALB/c
-
Ext1 and Ext2 are type II transmembrane glycoproteins
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant
-
EXTL1 and EXTL3 proteins from COS-1 cells
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression of full length and truncated form in Pichia pastoris and COS-1 cells, dramatic increase of activity when full length EXT1 and EXT2 are coexpressed, no increase of activity when mixing extract containing EXT1 and EXT2 protein
-
soluble form expressed in COS-7 cells
O77783
DV1, expression of soluble form of rib-2 protein in COS-1 cells
-
expression of soluble form in COS-1 cells
Q9XZ08
expressed in a C-terminal six-His fusion protein in BL21 star cells coexpressing chaperone proteins GroEL and GroES
-
expression of EXTL1, EXTL2 and EXTL3 in COS-1 cells, EXTL2 was found to show only N-acetyl-D-glucose transferase I activity, EXTL1 shows transferase II activity, EXTL3 shows transferase I and II activities
-
expression of soluble form of EXT1 and EXT2 proteins in COS-1 cells
-
completion of mutant sog9 with HeLa cDNA, restores susceptibility to HSV-1 infection
-
expression of full length and truncated form in Pichia pastoris and COS-1 cells, dramatic increase of activity when full length EXT1 and EXT2 are coexpressed, no increase of activity when mixing extract containing EXT1 and EXT2 protein
-
EXT1 and EXT2 from wild type CHO used to complement deficiency mutant CHO-K1, EXT2 failed to complement functional deficiency while it was fully corrected by EXT1
-
EXT1 used to complement deficiency mutant gro2C
-
full-length Ext1 cDNA cloned into the pBudCE4.1 vector and transfected into Ext1Gt/Gt fibroblasts
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C339D
-
resistant in HSV-1 infection assay
additional information
-
d620EXT1myc deletion mutant without 620 C-terminal amino acids, no enzymatic activity, ER localization
R340C
-
resistant in HSV-1 infection assay
additional information
-
enzyme null mutants, defects in Hedgehog and Decapentaplegic signalling, abnormal distribution of Wingless morphogen
additional information
-
enzyme null mutant, dramatically reduced levels of heparan sulfate, impaired Hedgehog, Wingless and Decapentaplegic signalling, alterations in chondroitin sulfate composition and levels
additional information
-
d620EXT1myc deletion mutant without 620 C-terminal amino acids, no enzymatic activity, ER localization
additional information
-
generation of conditional Ext1 mutant mice by crossing the Ext1flox allele and the Prx1-Cre transgene
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
analysis of enzyme mutations in patients with hereditary multiple exostoses, mutation spectrum