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Information on EC 2.4.1.224 - glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase and Organism(s) Bos taurus and UniProt Accession O77783

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IUBMB Comments
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.
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Bos taurus
UNIPROT: O77783
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The taxonomic range for the selected organisms is: Bos taurus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
exostosin-1, exostosin-2, tout-velu, sister of tout-velu, exostosin1, heparan sulfate polymerase, exostosin2, sister of tout velu, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
alpha-N-acetylglucosaminyltransferase II
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glucuronyl-N-acetylglucosaminoproteoglycan 4-alpha-N-acetylglucosaminyltransferase
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heparan sulfate polymerase
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N-acetyl-D-glucosaminyl-(N-acetyl-D-glucosamine) transferase
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UDP-GlcNAc:oligosaccharide beta-N-acetylglucosaminyltransferase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
transfer of alpha-N-acetylglucosamine
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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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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 + 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 + alpha-D-glucuronosyl-(1-4)-N-acetylglucoside
UDP + alpha-N-acetyl-D-glucosaminyl-alpha-D-glucuronosyl-(1-4)-N-acetylglucoside
show the reaction diagram
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-
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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 + [D-glucuronosyl-beta-(1->4)-N-acetyl-D-glucoseamin-alpha-(1->4)]n-D-glucuronosyl-2,5-anhydro-D-mannose
UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-[D-glucuronosyl-beta-(1->4)-N-acetyl-D-glucoseaminyl-alpha-(1->4)]n-D-glucuronosyl-2,5-anhydro-D-mannose
show the reaction diagram
additional information
?
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NATURAL SUBSTRATE
NATURAL 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 + 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
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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
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elongation of growing chains of heparin and heparan sulfate, tumor suppressor
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?
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Uniprot
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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transmembrane glycoprotein
Manually annotated by BRENDA team
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transmembrane glycoprotein
Manually annotated by BRENDA team
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
EXT2_BOVIN
718
1
81887
Swiss-Prot
Mitochondrion (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
70000
69000 - 71000
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SDS-PAGE
80000
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SDS-PAGE of expressed EXT1 and EXT2 proteins, weak band at 90000 D
90000
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SDS-PAGE of coexpressed EXT1 and EXT2, no second band detected
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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formation of homo- and heterooligomeric complexes of EXT1 and EXT2, heterooligomeric complexes have substantially higher glycosyltransferase activity than EXT1 or EXT2 has alone
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
soluble form expressed in COS-7 cells
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
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Senay, C.; Lind, T.; Muguruma, K.; Tone, Y.; Kitagawa, H.; Sugahara, K.; Lidholt, K.; Lindahl, U.; Kusche-Gullberg, M.
The EXT1/EXT2 tumor suppressors: catalytic activities and role in heparan sulfate biosynthesis
EMBO Rep.
1
282-286
2000
Bos taurus, Mus musculus, no activity in yeast
Manually annotated by BRENDA team
Lind, T.; Tufaro, F.; McCormick, C.; Lindahl, U.; Lidholt, K.
The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate
J. Biol. Chem.
273
26265-26268
1998
Mus musculus, Bos taurus (O77783)
Manually annotated by BRENDA team
Lidholt, K.; Lindahl, U.
Biosynthesis of heparin. The D-glucuronosyl- and N-acetyl-D-glucosaminyltransferase reactions and their relation to polymer modification
Biochem. J.
287
21-29
1992
Bos taurus, Mus musculus
-
Manually annotated by BRENDA team
Lind, T.; Lindahl, U.; Lidholt, K.
Biosynthesis of heparin/heparan sulfate. Identification of a 70-kDa protein catalyzing both the D-glucuronosyl- and the N-acetyl-D-glucosaminyltransferase reactions
J. Biol. Chem.
268
20705-20708
1993
Bos taurus
Manually annotated by BRENDA team
Lind, T.
Enzymes involved in heparan sulfate chain elongation
Trends Glycosci. Glycotechnol.
11
221-225
1999
Bos taurus, Cricetinae
-
Manually annotated by BRENDA team
McCormick, C.; Duncan, G.; Goutsos, K.T.; Tufaro, F.
The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the Golgi apparatus and catalyzes the synthesis of heapran sulfate
Proc. Natl. Acad. Sci. USA
97
668-673
2000
Bos taurus, Homo sapiens
Manually annotated by BRENDA team