Information on EC 2.4.1.225 - N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase

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

EC NUMBER
COMMENTARY hide
2.4.1.225
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RECOMMENDED NAME
GeneOntology No.
N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
UDP-alpha-D-glucuronate + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan = UDP + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan
show the reaction diagram
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Glycosaminoglycan biosynthesis - heparan sulfate / heparin
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heparan sulfate biosynthesis (late stages)
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
UDP-alpha-D-glucuronate:N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan 4-beta-glucuronosyltransferase
Involved in the biosynthesis of heparin and heparan sulfate. Some forms of the human enzyme (particularly the enzyme complex encoded by the EXT1 and EXT2 genes) act as bifunctional glycosyltransferases, which also have the glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase (EC 2.4.1.224) activity required for the synthesis of the heparan sulfate disaccharide repeats.
CAS REGISTRY NUMBER
COMMENTARY hide
145539-84-0
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene ext2
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Manually annotated by BRENDA team
K5
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Manually annotated by BRENDA team
K5
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Manually annotated by BRENDA team
Mus musculus BALB/c
gene sext1 and ext2
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
K5 heptasaccharide + UDP-alpha-D-glucuronate
?
show the reaction diagram
UDP-alpha-D-glucuronate + N-acetyl-alpha-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-proteoglycan
UDP + beta-glucuronosyl-(1-4)-N-acetyl-alpha-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-proteoglycan
show the reaction diagram
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
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
UDP-alpha-D-glucuronate + N-acetyl-alpha-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-proteoglycan
UDP + beta-glucuronosyl-(1-4)-N-acetyl-alpha-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-proteoglycan
show the reaction diagram
additional information
?
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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12000000 dpm 3H/mg; 6700000 dpm 14C/mg
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6
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EXT2, calculated
7.5
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heterodimer EXT1/EXT2, calculated
9
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EXT1, calculated
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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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
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peripheral chondrosarcoma; peripheral chondrosarcoma
Manually annotated by BRENDA team
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Sv40 embryonic cell line
Manually annotated by BRENDA team
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high level of EXT2 in EXT2-overexpressing mice
Manually annotated by BRENDA team
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enzyme EXT1
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
80000
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EXT2, gel filtration
81900
calculation from amino acid sequence
160000
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EXT1, and coexpressed EXT1/EXT2, gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
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2 * 80000, EXT1, calculated, 1 * 80000 + 1 * 80000, EXT1/EXT2 heterodimer, calculated
monomer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Drosophila melanogaster
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expressed in HEK-293 cells
expression in CHO cells
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expression in COS-7 cells as His/FLAG fusion protein
EXT1 and EXT2 cDNA, alone or in combination, cloned into the pBudCE4.1 vector, which contains two multiple cloning sites for simultaneous expression of two proteins. EXT1 cloned into the multiple cloning sites with the cytomegalovirus (CMV) immediate-early promotor and EXT2 into the multiple cloning sites with the human elongation factor 1alpha promotor. Constructs transfected into HEK-293 cells stably expressing NDST1 from the pCDNA3 vector. Mutated EXT2 cDNA cloned into the pBudCE4.1 vector and transfected into HEK-93 cells overexpressing NDST1. EXT2 cDNA inserted into the pCAGGS expression vector under the control of the CMV immediate-early enhancer and the chicken beta-actin promoter (CAG) for constitutively high tissue expression from fertilized eggs and early embryonic stage through adulthood. The cDNA construct cloned into the unique EcoR1 site between the CAG promoter and the rabbit beta-globin sequence. Vector linearized with BamH1 and SalI and injected into mice B6CBAF1 oocytes
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full-length Ext1 cDNA cloned into the pBudCE4.1 vector and transfected into Ext1Gt/Gt fibroblasts
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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the mutation status of patients with multiple osteochondromas correlates with decreased EXT1 or EXT2 expression, loss of EXT expression disrupts the function of the EXT1/2 complex in heparan sulfate proteoglycan biosynthesis, resulting in the intracellular accumulation of heparan sulfate proteoglycan core proteins in tumo tissues; the mutation status of patients with multiple osteochondromas correlates with decreased EXT1 or EXT2 expression, loss of EXT expression disrupts the function of the EXT1/2 complex in heparan sulfate proteoglycan biosynthesis, resulting in the intracellular accumulation of heparan sulfate proteoglycan core proteins in tumo tissues
Y419X
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the EXT2 mutation results in a truncated protein
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine