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
ganglio-series glycosphingolipids biosynthesis
-
-
Glycosphingolipid biosynthesis - ganglio series
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-
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
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
expression in CHO-Lec8 cells
-
-
Manually annotated by BRENDA team
strain O:36
-
-
Manually annotated by BRENDA team
alpha-L-iduronidase (IDUA) knockout mutant variant, gene B4GALNT1
SwissProt
Manually annotated by BRENDA team
-
Swissprot
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
-
UVB-irradiation of keratinocytes induces melanoma-associated ganglioside GM2/GD2 synthase gene in melanocytes via secretion of tumor necrosis factor alpha and interleukin 6
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-alpha-D-galactosamine + ganglioside GM3
UDP + ganglioside GM2
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-alpha-D-galactosamine + ganglioside GM3
UDP + ganglioside GM2
show the reaction diagram
Q00973
-
-
-
?
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
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not in detergent-solubilized enzyme assays, kinetics
ganglioside GT1b
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-
GD3
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GM3 as substrate
GM3
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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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-
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Heptylthioglucoside
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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
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-
0.0004 - 0.0005
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-
53.3
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pH 7.3, 37C, soluble domain
4566
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pH 7.3, 37C, membrane-bound complete enzyme
additional information
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-
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
-
high expression level
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
60000
-
2 * 60000, SDS-PAGE
64000
-
2 * 64000, SDS-PAGE
65000
-
2 * 65000, SDS-PAGE
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
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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
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expression in Escherichia coli strain AD202
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gene B4GALNT1, genotyping and linkage analysis
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gene B4GALNT1, quantitative enzyme expression analysis, mRNA expressions of glycosyltransferases by qRT-PCR in melanocytes and melanoma lines, overview
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gene B4GALNT1, semi-quantitative PCR enzyme expression analysis in brain tissues in wild-type and IDUA knockout mice
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression levels are reduced after UVB irradiation in SK-MEL-28 melanoma cells
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GM2/GD2 synthase expression is slightly increased in UVB-irradiated melanocytes, except for SK-MEL-28 cells
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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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tumor necrosis factor alpha and interleukin 6 do not affect the enzyme expression in in melanocytes
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
I285Y
-
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
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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