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

New: Word Map on EC 2.4.1.92
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


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

EC NUMBER
COMMENTARY
2.4.1.92
-
RECOMMENDED NAME
GeneOntology No.
(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase
-
REACTION
REACTION DIAGRAM
COMMENTARY
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
mechanism
-
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
residue 285 determines the donor substrate specificity of the enzyme, catalytic binding pocket structure, overview
-
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
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.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
acetylgalactosaminyltransferase
-
-
-
-
acetylgalactosaminyltransferase, uridine diphosphoacetylgalactosamine-ganglioside GM3
-
-
-
-
beta 1,4-N-acetylgalactosaminyltransferase-A
-
-
beta-(1-4)-N-acetylgalactosaminyltransferase
-
-
beta-(1-4)-N-acetylgalactosaminyltransferase
Campylobacter jejuni O:36
-
-
-
beta-(1->4)-N-acetylgalactosaminyltransferase
-
-
beta-1,4-N-acetylgalactosaminyl-transferase
-
-
beta-1,4-N-acetylgalactosyltransferase II
-
-
beta1,4-N-acetylgalactosaminyltransferase
-
-
beta4GalNAcT
-
-
beta4GalNAcT-II
-
-
beta4GalNAcTA
-
-
betaGalNAc-T4
-
CgtA
Campylobacter jejuni O:36
-
-
-
GA2/GM2/GD2/GT2-synthase
-
-
GALGT
-
-
Galgt1
-
gene name
GalNAcT
-
-
-
-
ganglioside GM2 synthase
-
-
-
-
ganglioside GM3 acetylgalactosaminyltransferase
-
-
-
-
GD2 synthase
-
GD2 synthetase
-
-
GD2/GM2 synthase
-
-
GD2/GM2 synthase
-
-
GM2 synthase
-
-
-
-
GM2 synthase
-
-
GM2 synthase
-
-
GM2/GD2 synthase
-
GM2/GD2-synthase
-
-
-
-
GM2S
-
-
GM3 synthase
-
-
GM3 synthase
-
-
GM3S
-
-
N-acetylgalactosaminyltransferase I
-
-
Sda beta-1,4-N-acetylgalactosaminyltransferase II
-
-
ST3Gal V
-
-
UDP acetylgalactosamine-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
-
-
-
-
UDP-N-acetylgalactosamine GM3 N-acetylgalactosaminyltransferase
-
-
-
-
UDP-N-acetylgalactosaminyltransferase I
-
-
-
-
uridine diphosphoacetylgalactosamine-acetylneuraminylgalactosylglucosylceramide
-
-
-
-
uridine diphosphoacetylgalactosamine-ganglioside GM3 acetylgalactosaminyltransferase
-
-
-
-
uridine diphosphoacetylgalactosamine-hematoside acetylgalactosaminyltransferase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
67338-98-1
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
expression in CHO-Lec8 cells
-
-
Manually annotated by BRENDA team
strain O:36
-
-
Manually annotated by BRENDA team
Campylobacter jejuni O:36
strain O:36
-
-
Manually annotated by BRENDA team
isoforms betaGalNAcTA and betaGalNAcTB
-
-
Manually annotated by BRENDA team
-
Swissprot
Manually annotated by BRENDA team
embryo
-
-
Manually annotated by BRENDA team
expression in baculovirus system, membrane-bound complete enzyme and soluble domain
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
in animals lacking either GM2/GD2 or GM3 synthase, tissue cholesterol concentrations and synthesis rates are normal in nearly all organs, and whole-animal sterol pools and turnover also are not different from control animals. Mice lacking both synthases, however, have small elevations in cholesterol concentrations in several organs, and the whole-animal cholesterol pool is marginally elevated. When either the GM2/GD2 or GM3 synthase activity is deleted in mice lacking Niemann-Pick type C function, the clinical phenotype is not changed, but lifespan is shortened.
malfunction
-
genes of complement components (C1qalpha, C1qbeta, C1qgamma, C4 and C3aR) are up-regulated in the cerebellum of mice with combined knockout of GM2/GD2 synthase and GD3 synthase
malfunction
-
GM3 synthase/GM2 synthase double knock out cells evidence significantly impaired tumor growth in syngeneic immunocompetent mice
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)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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
-
-
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 + (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 + (N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
UDP + N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
show the reaction diagram
-
-
i.e. GM2(N-acetylneuraminic acid)-ganglioside
?
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
-
-
i.e. GM2(N-acetylneuraminic acid)-ganglioside
?
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
-
-
i.e. GM2(N-acetylneuraminic acid)-ganglioside
?
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
-
-
i.e. GM2(N-acetylneuraminic acid)-ganglioside
?
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
-
73%-78% as effective as GM3(N-glycolylneuraminic acid)
i.e. GM2(N-acetylneuraminic acid)-ganglioside
?
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
-
73%-78% as effective as GM3(N-glycolylneuraminic acid)
i.e. GM2(N-acetylneuraminic acid)-ganglioside
?
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
-
from human spleen or rat liver
-
?
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
-
from human spleen or rat liver
i.e. GM2(N-acetylneuraminic acid)-ganglioside
?
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
-
less effective: GM3(O-acetyl-(N-glycolyl)neuraminic acid)
i.e. GM2(N-acetylneuraminic acid)-ganglioside
?
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
-
i.e. GM3(N-acetylneuraminic acid), best substrate
-
?
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
-
i.e. GM3(N-acetylneuraminic acid), best substrate
i.e. GM2(N-acetylneuraminic acid)-ganglioside
?
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
-
relative glycosyltransferase levels involved in determining the ganglioside composition of cells
-
?
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
-
model for ganglioside biosynthesis
-
?
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
-
involved in biosynthesis of gangliosides in brain
-
?
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
Campylobacter jejuni, Campylobacter jejuni O:36
-
ganglioside GM3
-
-
?
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
Campylobacter jejuni, Campylobacter jejuni O:36
-
-
-
?
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
Campylobacter jejuni, Campylobacter jejuni O:36
-
ganglioside GM2
-
-
?
UDP-N-acetyl-D-galactosamine + GD3-ganglioside
UDP + GD2-ganglioside
show the reaction diagram
-
-
-
?
UDP-N-acetyl-D-galactosamine + GD3-ganglioside
UDP + GD2-ganglioside
show the reaction diagram
-
-
-
?
UDP-N-acetyl-D-galactosamine + GD3-ganglioside
UDP + GD2-ganglioside
show the reaction diagram
-
-
-
?
UDP-N-acetyl-D-galactosamine + GD3-ganglioside
UDP + GD2-ganglioside
show the reaction diagram
-
GD3(N-glycolylneuraminic acid): 66% as effective as GM3(N-glycolylneuraminic acid), GD3(N-acetylneuraminic acid): 76% as effective as GM3(N-glycolylneuraminic acid)
-
?
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)
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
-
best substrate
-
?
UDP-N-acetyl-D-galactosamine + GM3(N-glycolylneuraminic acid)-ganglioside
UDP + GM2(N-glycolylneuraminic acid)-ganglioside
show the reaction diagram
-
best substrate
-
?
UDP-N-acetyl-D-galactosamine + GM3(N-glycolylneuraminic acid)-ganglioside
UDP + GM2(N-glycolylneuraminic acid)-ganglioside
show the reaction diagram
-
not as effective as GM3(N-acetylneuraminic acid)
-
?
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
-
?
human glycoprotein hormone alpha-subunit + ?
glycosylated human glycoprotein hormone alpha-subunit + ?
show the reaction diagram
-
-
-
-
additional information
?
-
-
acceptor specificity
-
-
-
additional information
?
-
-
poor substrate: GM2-, GM1-, GD1b- and GT1-gangliosides and various ceramides, no substrate: N-acetylglucosamine
-
-
-
additional information
?
-
-
overview on substrate specificity
-
-
-
additional information
?
-
-
no substrate: lactosylceramide, sialylparagloboside, GM1b(N-glycolylneuraminic acid), GD1a(N-acetylneuraminic acid), GT1b(N-acetylneuraminic acid), GQ1b(N-acetylneuraminic acid), GM1a(N-acetylneuraminic acid), GD1b(N-acetylneuraminic acid), globoside
-
-
-
additional information
?
-
-
no substrates are SM4-ganglioside, Gb3- and Gb4-ceramide
-
-
-
additional information
?
-
-
no substrate: blood type H glycoprotein, deglucosylated bovine submaxillary mucin, various ceramides
-
-
-
additional information
?
-
-
poor substrate: sialyllactose
-
-
-
additional information
?
-
enzyme shows similar specificities for O-and N-glykans. Efficiency of transfer decreases as the number of antennas increases
-
-
-
additional information
?
-
no in vitro transfer of substrates other than UDP-N-acetylgalactosamine to synthetic N-glycans
-
-
-
additional information
?
-
-
stable expression of enzyme in CHO-Lec8 cells, production of complex-type N-glycans quantitatively bearing LacdiNAc-structures on their antennae and containing repeating LacdiNAc-structures
-
-
-
additional information
?
-
-
during evolution, beta4Gal-T1 appears as a result of the single amino acid substitution of Tyr or Phe for Leu or Ile in the invertebrate beta4GalNAc-T1, overview
-
-
-
additional information
?
-
-
the enzyme synthesizes the LacdiNAc structures, with GalNAcbeta1,4GlcNAc, on several glycoproteins and glycosphingolipids, including N-glycans, O-glycans, and the arthro-series GSLs, GalNAcbeta1,4Glc-NAcbeta1,3Manbeta1,4Glcbeta1Cer, and neutral GSLs, in vitro and in vivo, the GalNAcbeta1,4GlcNAc, i.e. LacdiNAc or LDN, structure is a more common structural feature in invertebrate glycoconjugates when compared with the Galbeta1,4GlcNAc, i.e. LacNAc or LN, structure
-
-
-
additional information
?
-
-
carbohydrate-protein conjugate enzyme activity with truncated ceramides, analogues of GM3 and GM2 gangliosides, compound sythesis, overview
-
-
-
additional information
?
-
-
no activity with donor UDP-galactose, the enzyme synthesizes the LacdiNAc structures, with GalNAcbeta1,4GlcNAc, on several glycoproteins and glycosphingolipids, including N-glycans, O-glycans, and the arthro-series GSLs, such as GalNAcbeta1,4Glc-NAcbeta1,3Manbeta1,4Glcbeta1Cer, and neutral GSLs, in vitro and in vivo
-
-
-
additional information
?
-
-
the wild-type Drosophila beta4GalNAc-T1 enzyme binds to the mammary gland-specific protein alpha-lactalbumin
-
-
-
additional information
?
-
Campylobacter jejuni O:36
-
carbohydrate-protein conjugate enzyme activity with truncated ceramides, analogues of GM3 and GM2 gangliosides, compound sythesis, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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
-
relative glycosyltransferase levels involved in determining the ganglioside composition of cells
-
?
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
-
model for ganglioside biosynthesis
-
?
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
-
involved in biosynthesis of gangliosides in brain
-
?
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
-
ganglioside GM3
-
-
?
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-(N-acetyl-alpha-neuraminosyl)-(2-3)-O-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl]-ceramide
?
show the reaction diagram
Campylobacter jejuni O:36
-
ganglioside GM3
-
-
?
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
Campylobacter jejuni O:36
-
-
-
?
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
Campylobacter jejuni, Campylobacter jejuni O:36
-
ganglioside GM2
-
-
?
additional information
?
-
-
during evolution, beta4Gal-T1 appears as a result of the single amino acid substitution of Tyr or Phe for Leu or Ile in the invertebrate beta4GalNAc-T1, overview
-
-
-
additional information
?
-
-
the enzyme synthesizes the LacdiNAc structures, with GalNAcbeta1,4GlcNAc, on several glycoproteins and glycosphingolipids, including N-glycans, O-glycans, and the arthro-series GSLs, GalNAcbeta1,4Glc-NAcbeta1,3Manbeta1,4Glcbeta1Cer, and neutral GSLs, in vitro and in vivo, the GalNAcbeta1,4GlcNAc, i.e. LacdiNAc or LDN, structure is a more common structural feature in invertebrate glycoconjugates when compared with the Galbeta1,4GlcNAc, i.e. LacNAc or LN, structure
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
activation, 27% as effective as Mn2+
Cd2+
-
activation, can replace Mn2+ to some extent
Co2+
-
activation, can replace Mn2+ to some extent
Co2+
-
62% as effective as Mn2+
Cu2+
-
activation, can replace Ni2+ to some extent
Fe2+
-
activation, can replace Mn2+
Fe2+
-
activation, can replace Ni2+ to some extent, 17% as effective as Mn2+
Mg2+
-
activation, 22% as effective as Mn2+
Mn2+
-
requirement, 2.5-10 mM
Mn2+
-
can replace Ni2+ to some extent
Ni2+
-
can replace Mn2+ to some extent
Ni2+
-
5% as effective as Mn2+
Ni2+
-
requirement, most active, 10-20 mM
additional information
-
no activation by K+, Al3+
additional information
-
no activation by Ba2+
additional information
-
no activation by Zn2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
adenosine-5'-[alpha,beta-methylene]triphosphate
-
-
Chelex-100
-
-
-
ganglioside GD1a
-
-
ganglioside GM1
-
-
ganglioside GM2
-
-
ganglioside GQ1b
-
not in detergent-solubilized enzyme assays, kinetics
ganglioside GT1b
-
-
GD3
-
GM3 as substrate
GM3
-
GD3 as substrate
UDPgalactose
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cardiolipin
-
-
Detergents
-
CF-54, Tween 80
Detergents
-
requirement, solubilized enzyme, e.g. Triton X-100
Detergents
-
requirement, solubilized enzyme, e.g. Triton X-100
Endogen lipid factor
-
-
-
octylglucoside
-
activation; optimal: 0.8%
octylglucoside
-
activation
phosphatidylglycerol
-
activation, detergent-free assay
Triton CF-54
-
-
Triton X-100
-
-
Tween 80
-
-
Heptylthioglucoside
-
activation
additional information
-
promoter DNA methylation plays a crucial role in the regulation of the Sda beta4GalNAcT-II gene and Sda antigen expression
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.35
GD3(N-acetylneuraminic acid)
-
-
0.027
GD3(N-glycolylneuraminic acid)
-
-
-
0.0166
GM3
-
-
0.19
GM3
-
-
2.1
GM3(N-acetylneuraminic acid)
-
-
0.38
p-nitrophenyl-GlcNAc
pH 7.0, 37C
0.097
UDP-GalNAc
-
pH 7.3, 37C, soluble domain
0.19
UDP-GalNAc
-
pH 7.3, 37C, membrane-bound complete enzyme
0.007
UDP-N-acetyl-D-galactosamine
-
-
0.017
UDP-N-acetyl-D-galactosamine
-
-
0.026
UDP-N-acetyl-D-galactosamine
-
cosubstrate GM3
0.035
UDP-N-acetyl-D-galactosamine
-
-
0.057
UDP-N-acetyl-D-galactosamine
-
-
0.082
UDP-N-acetyl-D-galactosamine
-
cosubstrate SM3
1.64
UDP-N-acetylgalactosamine
pH 7.0, 37C
0.16
GM3(N-glycolylneuraminic acid)
-
-
additional information
additional information
-
kinetic study
-
additional information
additional information
-
assay method
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
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
LITERATURE
6.7 - 6.9
-
-
6.8 - 7.2
-
-
7.2 - 7.4
-
assay at
7.5 - 7.9
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
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
LITERATURE
37
-
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
adult and fetal
Manually annotated by BRENDA team
-
embryonic, postnatal, and adult brains
Manually annotated by BRENDA team
-
third instar larvae
Manually annotated by BRENDA team
additional information
-
not expressed on foreskin fibroblasts
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
dimerization occurs in the ER
Manually annotated by BRENDA team
-
functionally coupled to GD3 synthase
Manually annotated by BRENDA team
-
mitochondria-associated membrane, i.e. a membrane bridge between the endoplasmic reticulum and mitochondria
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
120000
-
gel filtration
489582
120000
-
PAGE
659865
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
2 * 65000, SDS-PAGE
dimer
-
2 * 64000, SDS-PAGE
dimer
-
2 * 60000, SDS-PAGE
additional information
-
probably enzyme complex with sialyltransferase II
additional information
-
enzyme is homodimer with antiparallel orientation of catalytic domains and intersubunit disulfide bonds
additional information
-
dimer formation occurs in ER, strategy to test for dimerization of Golgi membrane proteins
additional information
-
enzyme is functionally coupled to GD3 synthase
additional information
type II transmembrane protein
additional information
-
forms an in vivo complex with UDP-Gal:GA2/GM2/GD2/GT2 galactosyltransferase, complex assembles in the endoplasmic reticulum
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
all 3 glycosylation sites occupied by glycans, elimination of one or several sites leads to decrease in activity up to 90%
glycoprotein
-
3 N-glycosylation sites at 79,179, 274
additional information
protein has 3 potential N-gylcosylation sites and a DXH-sequence
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
glycerol, 20% v/v, stabilizes
-
detergents stabilize
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70C, 3 months, crude
-
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
-
-80C, several months, crude Triton X-100 extract
-
-80C, stable in 20% v/v glycerol, 1% v/v Triton X-100
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant FLAG-tagged catalytic domain from Spodoptera frugiperda Sf21 cells by anti-FLAG M1 affinity chromatography
-
Triton X-100 solubilized, affinity chromatography on GM3-acid Sepharose
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli strain AD202
-
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
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
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
V352A
-
167% of wild type activity
W354A
-
24% of wild type activity
additional information
-
site directed mutations in several Cys residues reveal that enzyme is homodimer with antiparallel orientation of catalytic domains and intersubunit disulfide bonds
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
additional information
-
isoform betaGalNAcTA null mutants are viable and fertile, but display behavioral phenotypes suggesting roles of enzyme in neuronal and/or muscle function. Isoform betaGalNAcTB null mutants are viable and show no evident morphological or behavioral phenotype. Double mutants display only the phenotypes associated with mutation of betaGalNAcTA
additional information
-
enzyme activity in beta4GalNAcT RNAi flies is reduced
additional information
-
beta4GalNAcTA null mutant larvae show frequent backward crawling, reductions in nerve terminal bouton number, decreased spontaneous transmitter release frequency, and short, wide, hypercontracted muscles with low calcium content, indicating a role for this enzyme in the neuromuscular system
D358A/D358N
-
variation of DXD motif, activity almost completely lost
additional information
-
3 different epitope-tagged forms of enzyme, enzyme is homodimer and has disulfide bonds, is localized to Golgi
additional information
-
elimination of one or several glycosylation sites leads to decrease in activity up to 90%
additional information
-
-
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
-
fusion protein with green, red or yellow fluorescent protein, localization to ER and Golgi, probably forms complex with sialyl-transferase II
additional information
-
overexpression of gene leads to shift of ganglioside components from b-series to a-series
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
-
stable expression of enzyme in CHO-Lec8 cells, production of complex-type N-glycans quantitatively bearing LacdiNAc-structures on their antennae and containing repeating LacdiNAc-structures
synthesis
-
the immobilized enzyme might be useful in chemoenzymatical ceramide glycoconjugate synthesis
synthesis
Campylobacter jejuni O:36
-
the immobilized enzyme might be useful in chemoenzymatical ceramide glycoconjugate synthesis
-
medicine
-
GD2 synthase is a surface marker for the identification of mesenchymal stromal cells
medicine
-
GD2/GM2 synthase mRNA is not a reliable biomarker for small cell lung cancer
synthesis
-
expression of enzyme both as complete membrane-bound enzyme and as a soluble form in the baculovirus insect cell expression system