Information on EC 2.4.1.92 - (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase

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

EC NUMBER
COMMENTARY hide
2.4.1.92
-
RECOMMENDED NAME
GeneOntology No.
(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
UDP-N-acetyl-alpha-D-galactosamine + O-(N-acetyl-alpha-neuraminyl)-(2->3)-O-beta-D-galactopyranosyl-(1->4)-beta-D-glucopyranosyl-(1<->1)-ceramide = UDP + O-2-(acetylamino)-2-deoxy-beta-D-galactopyranosyl-(1->4)-O-[N-acetyl-alpha-neuraminyl-(2->3)]-O-beta-D-galactopyranosyl-(1->4)-beta-D-glucopyranosyl-(1<->1)-ceramide
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexosyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Glycosphingolipid biosynthesis - ganglio series
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetyl-D-galactosamine:1-O-[O-(N-acetyl-alpha-neuraminosyl)-(2->3)-O-beta-D-galactopyranosyl-(1->4)-beta-D-glucopyranosyl]-ceramide 4-beta-N-acetyl-D-galactosaminyltransferase
This enzyme catalyses the formation of the gangliosides (i.e. sialic-acid-containing glycosphingolipids) GM2, GD2 and SM2 from GM3, GD3 and SM3, respectively. Asialo-GM3 [3] and lactosylceramide [2] are also substrates, but glycoproteins and oligosaccharides are not substrates.
CAS REGISTRY NUMBER
COMMENTARY hide
67338-98-1
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
expression in CHO-Lec8 cells
-
-
Manually annotated by BRENDA team
strain O:36
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-
Manually annotated by BRENDA team
-
Swissprot
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
-
GM3 synthase overexpression results in reduced cell motility accompanied by reduced levels of the epithelial-mesenchymal transition marker alpha smooth muscle actin and in caveolin-1 upregulation in human ovarian carcinoma cells
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
GM3(O-acetyl-(N-glycolyl)neuraminic acid) + UDP-N-acetyl-D-galactosamine
UDP + N-acetyl-D-galactosaminyl-GM3(O-acetyl-(N-glycolyl)neuraminic acid)
show the reaction diagram
-
less effective substrate
-
-
-
human glycoprotein hormone alpha-subunit + ?
glycosylated human glycoprotein hormone alpha-subunit + ?
show the reaction diagram
-
-
-
-
-
UDP-galactose + p-nitrophenyl-GlcNAc
UDP + Gal-beta(1-4)GlcNAc-p-nitrophenyl
show the reaction diagram
50% of activity with UDP-N-acetylgalactosamine
-
-
?
UDP-GalNAc + 12-azidododecyl 5-(acetylamino)-3,5-dideoxy-beta-L-altro-non-2-ulopyranonosyl-(2->3)-beta-D-galactopyranosyl-(1->4)-beta-D-glucopyranoside
UDP + 12-azidododecyl 2-(acetylamino)-2-deoxy-beta-D-galactopyranosyl-(1->4)-[5-(acetylamino)-3,5-dideoxy-beta-L-altro-non-2-ulopyranonosyl-(2->3)]-beta-D-galactopyranosyl-(1->4)-beta-D-glucopyranoside
show the reaction diagram
-
-
-
-
?
UDP-GalNAc + GlcNAcbeta1,3Fuc
UDP + GalNAcbeta1,4GlcNAcbeta1,3Fuc
show the reaction diagram
-
DNS-labeled acceptor substrate
-
-
?
UDP-GalNAc + n-octyl-beta-D-glucopyranoside
UDP + GalNAcbeta(1-4)-glc-n-octyl
show the reaction diagram
-
-
-
-
?
UDP-GalNAc + undec-10-enyl (5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->3)-beta-D-galactopyranosyl-(1->4)-beta-D-glucopyranoside
UDP + undec-10-enyl (5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->3)-[2-acetamido-2-deoxy-beta-D-galactopyranosyl-(1->4)]-beta-D-galactopyranosyl-(1->4)-beta-D-glucopyranoside
show the reaction diagram
-
-
-
-
?
UDP-GalNAc + undec-10-yn-1-yl 5-(acetylamino)-3,5-dideoxy-beta-L-altro-non-2-ulopyranonosyl-(2->3)-beta-D-galactopyranosyl-(1->4)-beta-D-glucopyranoside
UDP + undec-10-yn-1-yl 2-(acetylamino)-2-deoxy-beta-D-galactopyranosyl-(1->4)-[5-(acetylamino)-3,5-dideoxy-beta-L-altro-non-2-ulopyranonosyl-(2->3)]-beta-D-galactopyranosyl-(1->4)-beta-D-glucopyranoside
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-galactosamine + (N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
UDP + N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
show the reaction diagram
UDP-N-acetyl-D-galactosamine + 1-O-[O-(N-acetyl-alpha-neuraminosyl)-(2-3)-O-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl]-ceramide
?
show the reaction diagram
UDP-N-acetyl-D-galactosamine + 1-O-[O-(N-acetyl-alpha-neuraminosyl)-(2-3)-O-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl]-ceramide
UDP + 1-O-[O-2-(acetylamino)-2-deoxy-beta-D-galactopyranosyl-(1-4)-O-[N-acetyl-alpha-neuraminosyl-(2-3)]-O-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl]-ceramide
show the reaction diagram
UDP-N-acetyl-D-galactosamine + 1-O-[O-2-(acetylamino)-2-deoxy-beta-D-galactopyranosyl-(1-4)-O-[N-acetyl-alpha-neuraminosyl-(2-3)]-O-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl]-ceramide
?
show the reaction diagram
UDP-N-acetyl-D-galactosamine + GD3-ganglioside
UDP + GD2-ganglioside
show the reaction diagram
UDP-N-acetyl-D-galactosamine + GM3(N-glycolylneuraminic acid)
UDP + N-acetyl-D-galactosaminyl-GM3(N-glycolylneuraminic acid)
show the reaction diagram
UDP-N-acetyl-D-galactosamine + GM3(N-glycolylneuraminic acid)-ganglioside
UDP + GM2(N-glycolylneuraminic acid)-ganglioside
show the reaction diagram
UDP-N-acetyl-D-galactosamine + lactosylceramide
UDP + GA2-ganglioside
show the reaction diagram
-
-
-
?
UDP-N-acetyl-D-galactosamine + N-acetylneuraminelactose
UDP + N-acetyl-D-galactosaminyl-N-acetylneuraminelactose
show the reaction diagram
-
i.e. sialyllactose
-
-
?
UDP-N-acetyl-D-galactosamine + SM3-ganglioside
UDP + SM2-ganglioside
show the reaction diagram
-
best substrate, no substrates are SM4-ganglioside, Gb3- and Gb4-ceramide
-
-
?
UDP-N-acetylgalactosamine + GlcNAcbeta(1-3)GalNAcalpha-p-nitrophenol (core 3-p-nitrophenol)
UDP + GalNAcbeta(1-4)GlcNAcbeta(1-3)GalNAcalpha-p-nitrophenol
show the reaction diagram
20% of activity compared with N-acetylglucosamine-beta-benzyl
-
-
?
UDP-N-acetylgalactosamine + GlcNAcbeta(1-6)(Galbeta1-3)GalNAcalpha-p-nitrophenol (core 2-p-nitrophenol)
UDP + GalNAcbeta(1-4)GlcNAcbeta(1-6)(Galbeta1-3)GalNAcalpha-p-nitrophenol
show the reaction diagram
15.2% of activity compared with N-acetylglucosamine-beta-benzyl
-
-
?
UDP-N-acetylgalactosamine + GlcNAcbeta(1-6)GalNAcalpha-p-nitrophenol (core 6-p-nitrophenol)
UDP + GalNAcbeta(1-4)GlcNAcbeta(1-6)GalNAcalpha-p-nitrophenol
show the reaction diagram
190.7% of activity compared with N-acetylglucosamine-beta-benzyl
-
-
?
UDP-N-acetylgalactosamine + N-acetylglucosamine-beta-benzyl
N,N'-diacetyllactosediamine + benzol
show the reaction diagram
-
formation of beta-1,4-linkage
-
?
UDP-N-acetylgalactosamine + p-nitrophenyl-GlcNAc
UDP + GalNac-beta(1-4)GlcNAc-p-nitrophenyl
show the reaction diagram
-
-
-
?
UDP-N-acetylglucosamine + p-nitrophenyl-GlcNAc
UDP + GlcNAc-beta(1-4)GlcNAc-p-nitrophenyl
show the reaction diagram
50% of activity with UDP-N-acetylgalactosamine
-
-
?
additional information
?
-
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-galactosamine + (N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
UDP + N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
show the reaction diagram
UDP-N-acetyl-D-galactosamine + 1-O-[O-(N-acetyl-alpha-neuraminosyl)-(2-3)-O-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl]-ceramide
?
show the reaction diagram
UDP-N-acetyl-D-galactosamine + 1-O-[O-(N-acetyl-alpha-neuraminosyl)-(2-3)-O-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl]-ceramide
UDP + 1-O-[O-2-(acetylamino)-2-deoxy-beta-D-galactopyranosyl-(1-4)-O-[N-acetyl-alpha-neuraminosyl-(2-3)]-O-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl]-ceramide
show the reaction diagram
UDP-N-acetyl-D-galactosamine + 1-O-[O-2-(acetylamino)-2-deoxy-beta-D-galactopyranosyl-(1-4)-O-[N-acetyl-alpha-neuraminosyl-(2-3)]-O-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl]-ceramide
?
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cd2+
-
activation, can replace Mn2+ to some extent
Cu2+
-
activation, can replace Ni2+ to some extent
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
adenosine-5'-[alpha,beta-methylene]triphosphate
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-
Chelex-100
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-
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ganglioside GD1a
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-
ganglioside GM1
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-
ganglioside GM2
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-
ganglioside GQ1b
-
not in detergent-solubilized enzyme assays, kinetics
ganglioside GT1b
-
-
GD3
-
GM3 as substrate
GM3
-
GD3 as substrate
UDPgalactose
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-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cardiolipin
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-
Detergents
Endogen lipid factor
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-
-
Heptylthioglucoside
-
activation
octylglucoside
phosphatidylglycerol
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activation, detergent-free assay
Triton CF-54
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-
Triton X-100
Tween 80
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-
additional information
-
promoter DNA methylation plays a crucial role in the regulation of the Sda beta4GalNAcT-II gene and Sda antigen expression
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.35
GD3(N-acetylneuraminic acid)
-
-
0.027
GD3(N-glycolylneuraminic acid)
-
-
-
0.0166 - 0.19
GM3
2.1
GM3(N-acetylneuraminic acid)
-
-
0.16
GM3(N-glycolylneuraminic acid)
-
-
0.38
p-nitrophenyl-GlcNAc
pH 7.0, 37C
0.097 - 0.19
UDP-GalNAc
0.007 - 0.082
UDP-N-acetyl-D-galactosamine
1.64
UDP-N-acetylgalactosamine
pH 7.0, 37C
additional information
additional information
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000149
-
-
0.0004 - 0.0005
-
-
53.3
-
pH 7.3, 37C, soluble domain
4566
-
pH 7.3, 37C, membrane-bound complete enzyme
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.7 - 6.9
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-
6.8 - 7.2
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-
7.2 - 7.4
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assay at
7.5 - 7.9
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.2 - 8.5
-
about half-maximal activity at pH 6.2 and about 85% of maximal activity at pH 8.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
-
not expressed on foreskin fibroblasts
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
120000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
additional information
protein has 3 potential N-gylcosylation sites and a DXH-sequence
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
detergents stabilize
-
glycerol, 20% v/v, stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70C, 3 months, crude
-
-80C, several months, crude Triton X-100 extract
-
-80C, stable in 20% v/v glycerol, 1% v/v Triton X-100
-
4C, purified enzyme, at least 6 days in 20% v/v glycerol, 1% w/v heptylthioglucoside, 1 M sucrose, 0.2 M NaCl and 1 mM EDTA in 0.03 M cacodylate buffer, pH 6.9
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant FLAG-tagged catalytic domain from Spodoptera frugiperda Sf21 cells by anti-FLAG M1 affinity chromatography
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Triton X-100 solubilized, affinity chromatography on GM3-acid Sepharose
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme expression analysis in larvae, expression of the FLAG-tagged catalytic domain, comprisisng residues 62403, in the Spodoptera frugiperda Sf21 cell baculovirus expression system
-
expression in Escherichia coli strain AD202
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the transcriptional activity of GM3 synthase induced by valproic acid (2.4fold by 1 mM) in ARPE-19 cells is inhibited by SP600125. ATF2 binding to the CREB/ATF binding site at -143 is essential for transcriptional activation of the enzyme in valproic acid-induced ARPE-19 cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
I285Y
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site-directed mutagenesis, mutation of the residue to the human analogue results in change of substrate specificity from a beta4GalNAc-T1 to a beta4Gal-T1 by reducing its N-acetylgalactosaminyltransferase activity by nearly 1000fold, fold, while enhancing its galactosyltransferase activity by 80fold, overview
D356A/D356N
-
variation of DXD motif, activity almost completely lost
D356E
-
variation of DXD motif, weak activity
D356N/D357N/D358N
-
variation of DXD motif, activity almost completely lost, no alteration in nucleotide binding
D357N
-
variation of DXD motif, weak activity
D358A/D358N
-
variation of DXD motif, activity almost completely lost
V352A
-
167% of wild type activity
W354A
-
24% of wild type activity
Y285I
-
site-directed mutagenesis, mutation of the residue to the Drosophila melanogaster analogue results in change of substrate specificity from a beta4Gal-T1 to a beta4GalNAc-T1, overview
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
synthesis