Information on EC 2.4.99.9 - lactosylceramide alpha-2,3-sialyltransferase

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY hide
2.4.99.9
-
RECOMMENDED NAME
GeneOntology No.
lactosylceramide alpha-2,3-sialyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
CMP-N-acetylneuraminate + beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide = CMP + alpha-N-acetylneuraminyl-(2->3)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide
show the reaction diagram
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycosyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Glycosphingolipid biosynthesis - ganglio series
-
-
Metabolic pathways
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-
SYSTEMATIC NAME
IUBMB Comments
CMP-N-acetylneuraminate:beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide alpha-(2->3)-N-acetylneuraminyltransferase
Lactose cannot act as acceptor.
CAS REGISTRY NUMBER
COMMENTARY hide
125752-90-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
cichlid fish
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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in SAT-I null mice, hearing ability is impaired at the onset of hearing and is completely lost by 17 days after birth, showing a deformity in hair cells in the organ of Corti, by 2 months of age, the organ of Corti selectively and completely disappears without effect on balance or motor function or in the histology of vestibule. Lack of brainstem auditory-evoked potentials (BAEPs) in SAT-I null mice due to selective degeneration of the organ of Corti. SAT-I null mice maintain the function of stria vascularis. Defect of hearing ability of SAT-I null mice can be attributed to the functional disorganization of the organ of Corti, and the expression of gangliosides, especially GM3, during the early part of the functional maturation of the cochlea can be essential for the acquisition and maintenance of hearing function
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
CMP-N-acetylneuraminate + 1-deoxy-1-cholesteryl (N-acetyl)-ethanolaminolactitol
CMP + ?
show the reaction diagram
-
115% of activity with lactosylceramide
-
-
?
CMP-N-acetylneuraminate + 1-deoxy-1-cholesterylethanolaminolactitol
CMP + ?
show the reaction diagram
-
28% of activity with lactosylceramide
-
-
?
CMP-N-acetylneuraminate + 1-deoxy-1-cholesterylphospho (N-acetyl)-ethanolaminolactitol
CMP + ?
show the reaction diagram
-
151% of activity with lactosylceramide
-
-
?
CMP-N-acetylneuraminate + 1-deoxy-1-cholesterylphosphoethanolaminolactitol
CMP + ?
show the reaction diagram
-
60% of activity with lactosylceramide
-
-
?
CMP-N-acetylneuraminate + 2,3-dicholesteryl-1-beta-lactosylglycerol
?
show the reaction diagram
-
113% of activity with lactosylceramide
-
-
?
CMP-N-acetylneuraminate + 2-cholesteryl-1-beta-lactosylglycerol
?
show the reaction diagram
-
138% of activity with lactosylceramide
-
-
?
CMP-N-acetylneuraminate + 3-cholesteryl-1-beta-lactosylglycerol
?
show the reaction diagram
-
163% of activity with lactosylceramide
-
-
?
CMP-N-acetylneuraminate + asialoGM1
?
show the reaction diagram
-
27.7% relative activity to lactosylceramide
-
-
?
CMP-N-acetylneuraminate + asialoGM1
CMP + GM1
show the reaction diagram
-
-
-
?
CMP-N-acetylneuraminate + asialoGM2
CMP + GM2
show the reaction diagram
-
-
-
?
CMP-N-acetylneuraminate + beta-D-galactosyl-1,3-N-acetylgalactosamin-1,4-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + ?
show the reaction diagram
-
i.e. asialo-ganglioside GM1, sialylated at about 84% the rate of lactosylceramide
-
-
?
CMP-N-acetylneuraminate + beta-D-galactosyl-1,3-N-acetylgalactosamin-lactosylceramide
CMP + ?
show the reaction diagram
-
14% of activity with lactosylceramide
-
-
?
CMP-N-acetylneuraminate + beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
CMP-N-acetylneuraminate + beta-lactosylcholesterol
?
show the reaction diagram
-
138% of activity with lactosylceramide
-
-
?
CMP-N-acetylneuraminate + cholesteryl-beta-lactosylpropane-1,3-diol
?
show the reaction diagram
-
143% of activity with lactosylceramide
-
-
?
CMP-N-acetylneuraminate + galactosylceramide
?
show the reaction diagram
-
30% relative activity to lactosylceramide
-
-
?
CMP-N-acetylneuraminate + galactosylceramide
CMP + ?
show the reaction diagram
-
sialylated at about 40% the rate of lactosylceramide
-
-
?
CMP-N-acetylneuraminate + galactosylceramide
CMP + alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-ceramide
show the reaction diagram
-
-
-
?
CMP-N-acetylneuraminate + glucosylceramide
CMP + ?
show the reaction diagram
-
sialylated at about 65% the rate of lactosylceramide
-
-
?
CMP-N-acetylneuraminate + GM3
?
show the reaction diagram
-
4.5% relative activity to lactosylceramide
-
-
?
CMP-N-acetylneuraminate + lactosylceramide
?
show the reaction diagram
-
100% relative activity
-
-
?
CMP-N-acetylneuraminate + lactosylceramide
CMP + alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosyl-ceramide
show the reaction diagram
CMP-N-acetylneuraminate + lactosylceramide
CMP + N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
CMP-Neu5Ac + lactosylceramide
?
show the reaction diagram
-
caveolin-1 is a GM3-interacting protein in GM3 synthase overexpressing cells
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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
CMP-N-acetylneuraminate + lactosylceramide
CMP + alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosyl-ceramide
show the reaction diagram
CMP-N-acetylneuraminate + lactosylceramide
CMP + N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
activation, slightly less efficient than Mn2+
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(4-Amidinophenyl)-methanesulfonyl fluoride
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serine protease, 0.02 mM, 48% inhibition of purified sialyltransferase-1
alpha2-Macroglobulin
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1 unit, 67% inhibition of purified sialyltransferase-1, no inhibition of sialyltransferase-1 activity in microsomes
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Aprotinin
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serine protease inhibitor, 0.0003 mM, 74% inhibition of purified sialyltransferase-1
asialofetuin
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weak
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Cd2+
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strong
CMPdialdehyde
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kinetics
Cu2+
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strong
dithiothreitol
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0.1 mM, 89% inhibition of purified sialyltransferase-1
DL-threo-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol
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inhibitor of ganglioside synthesis, depletion of GM3 synthesis in cultured monocyte-derived macrophages, delays acquisition of CD206 antigen, prevents loss of CD163 antigen and enhances anti-inflammatory cytokine (CCL18) secretion
E-64
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thiol protease inhibitor, 0.0028 mM, 71% inhibition of purified sialyltransferase-1, activation of sialytransferase-1 activity in microsomes
EDTA
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0.1 mM, 71% inhibition of purified sialyltransferase-1
Ep-475
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thiol protease inhibitor, 0.0028 mM, 75% inhibition of purified sialyltransferase-1; thiol protease inhibitor, 0.0028 mM, 84% inhibition of purified sialyltransferase-1
ganglioside GM1a
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-
ganglioside GM3
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0.5 mM and 1 mM, 43% and 60% inhibition respectively
Globotetraosylceramide
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weak
Go6976
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protein kinase C inhibitor, treatment of phorbol 12-myristate 13-acetate induced cells reduces expression of GM3 synthase
Ionic detergents
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-
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L-1-chloro-3-[4-tosylamido]-4-phenyl-2-butanone
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chymotrypsin and thiol protease inhibitor, 0.284 mM, 67% inhibition of purified sialyltransferase-1
L-1-Chloro-3-[4-tosylamido]-7-amino-2-heptanone-HCl
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trypsin and thiol protease inhibitor, 0.135 mM, 73% inhibition of purified sialyltransferase-1
Leupeptin
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serine and thiol protease inhibitor, 0.001 mM, 72% inhibition of purified sialyltransferase-1, no inhibition of sialyltransferase-1 activity in microsomes
Monoclonal antibody M12GC7
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-
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N3-
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1 mM, 87% inhibition of purified sialyltransferase-1
Ni2+
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strong
pepstatin A
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0.001 mM, 72% inhibition of purified sialyltransferase-1, activation of sialyltransferase-1 activity in microsomes
Tris buffer
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weak
Triton CF-54
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at higher concentrations
U0126
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extracellular signal-regulated kinase inhibitor, treatment of phorbol 12-myristate 13-acetate induced cells reduces expression of GM3 synthase
UDP-N-acetylgalactosamine
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weak
UDPdialdehyde
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kinetics
UDPgalactose
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weak
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
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0.18 mM, 392% activation of purified sialyltransferase-1, 1120% activation of sialytransferase-1 activity in microsomes
beta-octylglucoside
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-
cardiolipin
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activation
Cutscum
Lauryldimethylamine oxide
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i.e. Ammonyx LO, nonionic/cationic detergent, 12-15fold higher activation than by Triton CF-54, Triton X-100 or beta-octylglucoside
Myrj 59
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activation, most potent activator, can be replaced by sodium deoxycholate, Triton CF-54, Tween 20, Triton CF-54/Tween 80, ratio 2:1, Triton X-100 or Tween 80, activation efficiency in descending order
Nonidet P-40
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slight activation
Triton CF-54
Triton CF-54/Tween 80
Triton X-100
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00026 - 1.5
CMP-N-acetylneuraminate
0.00011 - 0.11
lactosylceramide
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0853 - 0.104
CMP-dialdehyde
0.219
UDP-dialdehyde
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at 0.2 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000000167
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homogenate
0.0000027
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sialyltransferase-1 activity in membrane fraction from brain
0.0000032
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liver
0.0000045
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-
0.0000064
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sialyltransferase-1 activity in membrane fraction from brain
0.00002255
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PMA-stimulated HL-60 cell
0.0006048
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3600fold purified enzyme
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.4
assay at; assay at
additional information
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.1 - 7.6
-
detectable activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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expression of GM3S mRNA is greater in the highly metastatic 4T1 tumor cells than in the nonmetastatic 67NR cells
Manually annotated by BRENDA team
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in atherosclerosis, excessive GM3 is synthesized in atherosclerotic lesions by macrophages and dendritic cells directly within the arterial walls in blood arteries additionally to the GM3 synthesis in blood plasma, the fatty acid compositions of GM3 from blood plasma low density lipoprotein and from atherosclerotic lesions differ; level of GM3 synthase in membrane-fractions isolated from the atherosclerotic intima are higher compared to those in non-dieased arterial tissue
Manually annotated by BRENDA team
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in atherosclerosis, excessive GM3 is synthesized in atherosclerotic lesions by macrophages and dendritic cells directly within the arterial walls in blood vessels additionally to the GM3 synthesis in blood plasma, the fatty acid compositions of GM3 from blood plasma low density lipoprotein and from atherosclerotic lesions differ
Manually annotated by BRENDA team
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; excessive GM3 is synthesized in atherosclerotic lesions by macrophages and dendritic cells directly within the arterial walls
Manually annotated by BRENDA team
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contact-inhibited cell-line NIL-8
Manually annotated by BRENDA team
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high transcript level of SAT-Ia and SAT-Ib transcript
Manually annotated by BRENDA team
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strain R, elevated enzyme level if cultured in butyrate containing media
Manually annotated by BRENDA team
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high levels of SAT-Ia-1 and SAT-Ia-2, whereas very low levels of SAT-Ib-1 and SAT-Ib-2
Manually annotated by BRENDA team
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murine neuroblastoma x rat dorsal root ganglion F-11A cells
Manually annotated by BRENDA team
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high levels of SAT-Ia-1 and SAT-Ia-2, whereas very low levels of SAT-Ib-1 and SAT-Ib-2
Manually annotated by BRENDA team
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embryonic carcinoma cell line P19 differentiates into neurons and astrocytes on cell aggregation after treatment with retinoic acid
Manually annotated by BRENDA team
type 5 isozyme
Manually annotated by BRENDA team
-
high levels of SAT-Ia-1 and SAT-Ia-2, whereas very low levels of SAT-Ib-1 and SAT-Ib-2
Manually annotated by BRENDA team
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high levels of SAT-Ia-1 and SAT-Ia-2, whereas very low levels of SAT-Ib-1 and SAT-Ib-2
Manually annotated by BRENDA team
-
high levels of SAT-Ia-1 and SAT-Ia-2, whereas very low levels of SAT-Ib-1 and SAT-Ib-2
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
-
M1-SAT-I, M2-SAT-I, and M3-SAT-I possess distinct lengths in their NH2-terminal cytoplasmic tails
-
Manually annotated by BRENDA team
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
56
-
t1/2: 60 s
100
-
5 min, inactivation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
lauryldimethylamine oxide solubilizes and stabilizes solubilized enzyme during purification and storage
-
PMSF, leupeptin or pepstatin A stabilize during purification
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, 25 mM sodium cacodylate, pH 6.5, 15% w/v lauryldimethylamine oxide, 6-12 months, no loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
by immunoaffinity chromatography, to apparent homogeneity, 3600fold, with a yield of 19%
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
CHO cells transfected with hSAT-Ia-1 or -Ia-2 including the 5'-UTR
-
CHO cells transiently transfected with plasmids encoding SAT-Ia or SAT-Ib, which contains the 5'-untranslated region of each variant. CHO cells stably transfected with ks-M1-SAT-I, ks-M2-SAT-I, or ks-M3-SAT-I, in which GCCACC (ks) is inserted before isoforms M1, M2, or M3. Stable expression in CHO cells of a fusion protein for the NH2-terminus of M1-, M2-, or M3-SAT-I containing the transmembrane region and EGFP (M1-SAT-I(N)-EGFP, M2-SAT-I(N)-EGFP, and M3-SAT-I(N)-EGFP or each M1-SAT-I(N)-EGFP mutant)
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cloning from HL-60 cells, DNA and amino acid sequence determination and analysis, genetic organization of isozymes, mRNA variants differ in the 5'-untranslated region, in vitro transcription and translation using the rabbit reticulocyte lysate system, expression in murine MG1361 cells, a mammary adenocarcinoma cell line; cloning from placenta, DNA and amino acid sequence determination and analysis, genetic organization of isozymes, mRNA variants differ in the 5'-untranslated region, in vitro transcription and translation using the rabbit reticulocyte lysate system, expression in murine MG1361 cells, a mammary adenocarcinoma cell line; type 1-4 isozymes, DNA and amino acid sequence determination and analysis, genetic organization of isozymes, mRNA variants differ in the 5'-untranslated region, in vitro transcription and translation using the rabbit reticulocyte lysate system, expression in murine MG1361 cells, a mammary adenocarcinoma cell line
expression as fusion proteins with red fluorescent protein in murine neuroblastoma F-11A cells
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from HL-60 cell DNA, expression of His6-tagged fragment comprising residues 191-245
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functional expression in HT22 cells, GM3 levels are increased in immortalized mouse hippocampal HT22 cells after exposure to glutamate, GM3 not only mediates the effect of glutamate on the oxidative death of HT22 cells but also acts, in itself, as a modulator of in vivo neuronal cell death, overview
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SAT-1 cDNA cloned into plasmid expression vector pRc/CMV under control of CMV promoter, overexpression in A2780 ovarian tumor cells
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three pairs of oligonucleotides, corresponding to different regions of murine GM3S encoding gene, annealed and inserted into BglII/HindIII double digested pMEHMpuro, yielding the vectors pMEHM-siGM3S1, pMEHM-siGM3S2, and pMEHMsiGM3S3. Full-length GM3S encoding gene amplified from the total RNA of 4T1 cells and inserted into XhoI/EcoRI double digested pMSCVpuro, resulting in the GM3S expression vector pMSCV-GM3S. Overexpressed in non-metastatic 67NR cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme mRNA levels are significantly lower (64%) in mouse muscles of a model of hereditary inclusion body myopathy harboring the M712T mutation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase compared to control mice
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expression level of M3-SAT-I decreases remarkably in cells carrying the mSAT-Ib m1 in which the nucleotide sequence from position -6 to -1 at the M2 site is switched for GCCACC
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expression of GM3S in the highly metastatic 4T1 cell line silenced by RNA interference. Expression of the GM3S siRNAs siGM3S2 and siGM3S3, but not that of siGM3S1, drastically reduces expression of GM3S mRNA in 4T1 cells
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GM3 synthase mRNA is significantly increased (mediated by specificity protein 1) in transforming growth factor-beta1-induced HLE B-3 cells
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GM3 synthase mRNA levels are significantly higher in differentiated monocyte-derived macrophages compared to monocytes and in atherosclerotic aorta compared to normal aorta
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overexpressed in 67NR cells
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SAT-1 mRNA level and GM3 synthase activity in vitro are markedly upregulated in 3 SAT-1-transfected clones with respect to wild-type and mock-transfected A2780 cells
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the activity of GM3 synthase in blood mononuclear cells from atherosclerotic patients is 4.6fold higher than those from healthy subjects
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the transcriptional activity of the enzyme is induced 2.4fold by 1 mM valproic acid in ARPE-19 cells
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valproic acid induces hST3Gal V mRNA expression in SK-N-BE(2)-C cells. A cAMP-responsive element at -143 is essential for transcriptional activation of hST3Gal V in valproic acid-induced SK-N-BE(2)-C cells. Subsequent cAMP-responsive element binding protein binding to this cAMP-responsive element mediates valproic acid-dependent upregulation of hST3Gal V gene expression
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
DELTA12-21
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M1-SAT-I(N)-EGFP mutant, is localized in the Golgi apparatus
DELTA12-26
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M1-SAT-I(N)-EGFP mutant, is localized in the Golgi apparatus
DELTA28-55
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M1-SAT-I(N)-EGFP mutant, changes its localization from the endoplasmic reticulum to the Golgi apparatus
M28/56A
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ks-M1-SAT-I mutant, subcellular localization and stability similar to those of the wild-type. Activity is similar to that of ks-M1-SAT-I. Amounts of gangliosides in the ks-M1-SAT-I M28/56A mutant-transfected cells are greatly reduced compared with those of cells transfected with the other isoforms or mutants
M29A
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ks-M1-SAT-I mutant, activity is decreased to ca. 50%, relative to the activity of ks-M2-SAT-I
R11S
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M1-SAT-I(N)-EGFP mutant, is localized in the endoplasmic reticulum
R11S/R12S
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M1-SAT-I(N)-EGFP mutant, results in a shift of localization from the endoplasmic reticulum to the Golgi apparatus
R11S/R17S
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M1-SAT-I(N)-EGFP mutant, shifts its localization to the Golgi apparatus
R12S
-
M1-SAT-I(N)-EGFP mutant, is localized in the endoplasmic reticulum
R12S/R17S
-
M1-SAT-I(N)-EGFP mutant, shifts its localization to the Golgi apparatus
R17S
-
M1-SAT-I(N)-EGFP mutant, stays in the endoplasmic reticulum
additional information
-
overexpression of recombinant UDP-GlcNAc 2-epimerase/ManNAc 6-kinase, GNE, in HEK AD293 cells up-regulates GM3 synthase, while GNE down-regulation by RNA interference or exogenous GM3 and GD3 down-regulates the GM3 synthase
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine