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 hide
2.4.1.224
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RECOMMENDED NAME
GeneOntology No.
glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
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
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
transfer of alpha-N-acetylglucosamine
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
heparan sulfate biosynthesis (late stages)
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Glycosaminoglycan biosynthesis - heparan sulfate / heparin
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Metabolic pathways
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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, glucuronosyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase.
CAS REGISTRY NUMBER
COMMENTARY hide
145539-84-0
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336193-98-7
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene ext2
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Manually annotated by BRENDA team
gene sext1 and ext2
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Manually annotated by BRENDA team
no activity in yeast
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
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Exostosin glycosyltransferases exclusively catalyze heparan sulfate polymerization. Heparan sulfate/heparin, chondroitin sulfate, dermatan sulfate, and keratan sulfate form glycosaminoglycans, long linear polysaccharide chains consisting of repeat disaccharide units. Glycosaminoglycans are the major components of the extracellular matrix and play critical roles in regulating transport and signaling of numerous growth factors during embryonic development
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
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
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?
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 + N-acetylheparosan oligosaccharide
?
show the reaction diagram
with terminal nonreducing glucuronic acid
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?
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
UDP-N-acetyl-D-glucosamine + [mannose]5-N-acetyl-D-glucosamine
?
show the reaction diagram
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?
UDP-N-acetyl-D-glucosamine + [mannose]9-N-acetyl-D-glucosamine
?
show the reaction diagram
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?
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-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
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
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required, can not be substituted by other divalent cations
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Detergent
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required, range from 0.03-1%
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.65
(mannose)9 -N-acetyl-D-glucosamine
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0.094 - 1.2
UDP-N-acetyl-D-glucosamine
0.006
[D-glucuronic acid-N-acetyl-glucosamine]14 -D-glucuronic acid-2,5-anhydro-D-mannose
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0.06
[D-glucuronic acid-N-acetyl-glucosamine]4 -D-glucuronic acid-2,5-anhydro-D-mannose
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additional information
additional information
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KM-values for the disaccahride, tetrasaccharide, hexasaccharide and octasaccharide acceptors
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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specific activities of different pgsD mutants tested
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 7.2
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broad optimum
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 8
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5.2 - 8.4
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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
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
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enzyme EXT1
Manually annotated by BRENDA team
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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
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EXT1
Manually annotated by BRENDA team
additional information
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zebrafish ext2 gene is ubiquitously expressed during zebrafish development
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
69000 - 71000
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SDS-PAGE
70000
SDS-PAGE, purified enzyme; SDS-PAGE, soluble form
86300
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EXT1
88000
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SDS-PAGE, species two with second species with MW 91000
91000
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SDS-PAGE, species one with second species with MW 88000
110000
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expressed fusion protein from COS-1after N-glycosidase treatment, SDS-PAGE
130000
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expressed fusion protein from COS-1, SDS-PAGE
160000
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EXT1, and coexpressed EXT1/EXT2, gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 27000, SDS-PAGE
dimer
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2 * 80000, EXT1, calculated, 1 * 80000 + 1 * 80000, EXT1/EXT2 heterodimer, calculated
monomer
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80000, EXT2, calculated
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Rti regulates the stability of EXT isozymes
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
EXTL1 and EXTL3 proteins from COS-1 cells
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recombinant
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
completion of mutant sog9 with HeLa cDNA, restores susceptibility to HSV-1 infection
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DV1, expression of soluble form of rib-2 protein in COS-1 cells
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expressed in a C-terminal six-His fusion protein in BL21 star cells coexpressing chaperone proteins GroEL and GroES
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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
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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
expression of soluble form in COS-1 cells
expression of soluble form of EXT1 and EXT2 proteins in COS-1 cells
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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
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EXT1 used to complement deficiency mutant gro2C
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full-length Ext1 cDNA cloned into the pBudCE4.1 vector and transfected into Ext1Gt/Gt fibroblasts
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gene EXT1, creation of loxP-modified Ext1 allele and establishment of the Ext1 floxed mouse line (Ext1flox/flox), expression of the enzyme in Gdf-5-Cre transgenic mice, semiquantitative real-time PCR enzyme expression analysis
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gene EXT1, recombinant expression of Myc-DKK-tagged enzyme in S2 cells, interaction analysis with GOLPH3 via yeast two-hybrid assay; gene EXT2, recombinant expression of Myc-DKK-tagged enzyme in S2 cells, interaction analysis with GOLPH3 via yeast two-hybrid assay
gene EXT2, genotyping, autozygosity mapping
soluble form expressed in COS-7 cells
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C339D
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resistant in HSV-1 infection assay
R340C
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resistant in HSV-1 infection assay
C333R
naturally occuring mutation in hereditary multiple exostoses syndrome
L462W
naturally occuring mutation in hereditary multiple exostoses syndrome
L46F
naturally occuring mutation in hereditary multiple exostoses syndrome
M87R
naturally occuring mutation from a patient with clinical seizures-scoliosis-macrocephaly syndrome
N288K
naturally occuring mutation in hereditary multiple exostoses syndrome
R227D
naturally occuring mutation in hereditary multiple exostoses syndrome
R340H
naturally occuring mutation in hereditary multiple exostoses syndrome
R95C
naturally occuring mutation from a patient with clinical seizures-scoliosis-macrocephaly syndrome
S344F
naturally occuring mutation in hereditary multiple exostoses syndrome
S478L
naturally occuring mutation in hereditary multiple exostoses syndrome
V68G
naturally occuring mutation in hereditary multiple exostoses syndrome
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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analysis of enzyme mutations in patients with hereditary multiple exostoses, mutation spectrum
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