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Information on EC 2.4.1.92 - (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase and Organism(s) Homo sapiens
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2.4.1.92 (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferaseIUBMB Comments
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 and lactosylceramide are also substrates, but glycoproteins and oligosaccharides are not substrates.
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Word Map
- 2.4.1.92
- glycosphingolipids
- gd3
-
sialic
- lactosylceramide
- glycosyltransferases
-
sialyltransferase
-
laccer
- udp-galnac
-
a-series
-
hst3gal
-
anti-gm3
-
infantile-onset
- synthesis
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
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Synonyms
gm3 synthase, gm2 synthase, gm2/gd2 synthase, gd2 synthase, gd2/gm2 synthase, beta1,4-n-acetylgalactosaminyltransferase, beta4galnacta, n-acetylgalactosaminyltransferase i, galgt1, st3gal v, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acetylgalactosaminyltransferase
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acetylgalactosaminyltransferase, uridine diphosphoacetylgalactosamine-ganglioside GM3
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GalNAcT
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ganglioside GM2 synthase
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ganglioside GM3 acetylgalactosaminyltransferase
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GM2 synthase
GM2/GD2-synthase
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UDP acetylgalactosamine-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
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UDP-N-acetylgalactosamine GM3 N-acetylgalactosaminyltransferase
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UDP-N-acetylgalactosaminyltransferase I
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uridine diphosphoacetylgalactosamine-acetylneuraminylgalactosylglucosylceramide
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uridine diphosphoacetylgalactosamine-ganglioside GM3 acetylgalactosaminyltransferase
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uridine diphosphoacetylgalactosamine-hematoside acetylgalactosaminyltransferase
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GM2 synthase
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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
residue 285 determines the donor substrate specificity of the enzyme, catalytic binding pocket structure, overview
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexosyl group transfer
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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
67338-98-1
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
UDP-N-acetyl-alpha-D-galactosamine + ganglioside GM3
UDP + ganglioside GM2
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-
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?
UDP-N-acetyl-D-galactosamine + (N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
UDP + N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
UDP-N-acetylgalactosamine + GlcNAcbeta(1-3)GalNAcalpha-p-nitrophenol (core 3-p-nitrophenol)
UDP + GalNAcbeta(1-4)GlcNAcbeta(1-3)GalNAcalpha-p-nitrophenol
20% of activity compared with N-acetylglucosamine-beta-benzyl
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-
?
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
15.2% of activity compared with N-acetylglucosamine-beta-benzyl
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-
?
UDP-N-acetylgalactosamine + GlcNAcbeta(1-6)GalNAcalpha-p-nitrophenol (core 6-p-nitrophenol)
UDP + GalNAcbeta(1-4)GlcNAcbeta(1-6)GalNAcalpha-p-nitrophenol
190.7% of activity compared with N-acetylglucosamine-beta-benzyl
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-
?
UDP-N-acetylgalactosamine + N-acetylglucosamine-beta-benzyl
N,N'-diacetyllactosediamine + benzol
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formation of beta-1,4-linkage
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?
UDP-N-acetyl-D-galactosamine + (N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
UDP + N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
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-
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?
UDP-N-acetyl-D-galactosamine + (N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
UDP + N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
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from human spleen or rat liver
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-
?
UDP-N-acetyl-D-galactosamine + (N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
UDP + N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
i.e. GM3(N-acetylneuraminic acid), best substrate
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-
?
UDP-N-acetyl-D-galactosamine + (N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
UDP + N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
relative glycosyltransferase levels involved in determining the ganglioside composition of cells
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?
UDP-N-acetyl-D-galactosamine + GD3-ganglioside
UDP + GD2-ganglioside
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?
additional information
?
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enzyme shows similar specificities for O-and N-glykans. Efficiency of transfer decreases as the number of antennas increases
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?
additional information
?
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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
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
UDP-N-acetyl-alpha-D-galactosamine + ganglioside GM3
UDP + ganglioside GM2
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-
-
?
UDP-N-acetyl-D-galactosamine + (N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
UDP + N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
relative glycosyltransferase levels involved in determining the ganglioside composition of cells
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-
?
additional information
?
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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
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-
?
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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promoter DNA methylation plays a crucial role in the regulation of the Sda beta4GalNAcT-II gene and Sda antigen expression
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
mutations in gene B4GALNT1 are the cause of an unusual neurodegenerative phenotype, most commonly classified as a complex form of hereditary spastic paraplegia, present in families from Kuwait, Italy and the Old Order Amish. Biochemical profiling of glycosphingolipid biosynthesis confirms a lack of GM2 in affected subjects in association with a predictable increase in levels of its precursor, GM3. In the absence of functional GM2 synthase in the patient cells, there will be a lack of downstream glycosphingolipids as substrates for sialyltransferase, ST3GALII, and this may be the cause of the ectopic sialylation of Gb3
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
metabolism
the enzyme catalyzes the second step in complex ganglioside biosynthesis
metabolism
the enzyme is part of the biosynthetic pathway of glycosphingolipids, overview
physiological function
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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
physiological function
GM2 synthase is a GalNAc transferase responsible for synthesizing GM2, GA2 and GD2. GM2 ganglioside is a sialylated glycosphingolipid that is synthesized in the Golgi apparatus as part of a complex biosynthetic pathway
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). B4GN1_HUMAN
533
1
58882
Swiss-Prot
Secretory Pathway (Reliability: 2)
F8TDK6_HUMAN
173
0
18410
TrEMBL
other Location (Reliability: 2)
F8TDK7_HUMAN
196
0
20820
TrEMBL
other Location (Reliability: 2)
F8TDK5_HUMAN
121
0
12772
TrEMBL
other Location (Reliability: 2)
F8TDK4_HUMAN
173
0
18439
TrEMBL
other Location (Reliability: 2)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
dimer formation occurs in ER, strategy to test for dimerization of Golgi membrane proteins
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
additional information
protein has 3 potential N-gylcosylation sites and a DXH-sequence
glycoprotein
all 3 glycosylation sites occupied by glycans, elimination of one or several sites leads to decrease in activity up to 90%
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D356N/D357N/D358N
variation of DXD motif, activity almost completely lost, no alteration in nucleotide binding
Y285I
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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
additional information
3 different epitope-tagged forms of enzyme, enzyme is homodimer and has disulfide bonds, is localized to Golgi
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%
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene B4GALNT1, quantitative enzyme expression analysis, mRNA expressions of glycosyltransferases by qRT-PCR in melanocytes and melanoma lines, overview
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression levels are reduced after UVB irradiation in SK-MEL-28 melanoma cells
GM2/GD2 synthase expression is slightly increased in UVB-irradiated melanocytes, except for SK-MEL-28 cells
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Senn, H.J.; Cooper, C.; Warnke, P.C.; Wagner, M.; Decker, K.
Ganglioside biosynthesis in rat liver. Characterization of UDP-N-acetylgalactosamine - GM3 acetylgalactosaminyltransferase
Eur. J. Biochem.
120
59-67
1981
Homo sapiens, Rattus norvegicus
Nagata, Y.; Yamashiro, S.; Yodoi, J.; Lloyd, K.O.; Shiku, H.; Furukawa, K.
Expression cloning of beta 1,4 N-acetylgalactosaminyltransferase cDNAs that determine the expression of GM2 and GD2 gangliosides [published erratum appears in J Biol Chem 1994 Mar 4;269(9):7045]
J. Biol. Chem.
267
12082-12089
1992
Homo sapiens
Jaskiewicz, E.; Zhu, G.; Taatjes, D.J.; Darling, D.S.; Zwanzig, G.E., Jr.; Young, W.W., Jr.
Cloned beta1,4N-acetylgalactosaminyltransferase: subcellular localization and formation of disulfide bonded species
Glycoconjugate J.
13
213-223
1996
Homo sapiens (Q00973), Homo sapiens
Zhu, G.; Jaskiewicz, E.; Bassi, R.; Darling, D.S.; Young, W.W., Jr.
beta1,4 N-Acetylgalactosaminyltransferase (GM2/GD2/GA2 synthase) forms homodimers in the endoplasmic reticulum: a strategy to test for dimerization of Golgi membrane proteins
Glycobiology
7
987-996
1997
Homo sapiens (Q00973)
Haraguchi, M.; Yamashiro, S.; Furukawa, K.; Takamiya, K.; Shiku, H.; Furukawa, K.
The effects of the site-directed removal of N-glycosylation sites from beta-1,4-N-acetylgalactosaminyltransferase on its function
Biochem. J.
312
273-280
1995
Homo sapiens (Q00973)
-
Ruan, S.; Raj, B.K.M.; Furukawa, K.; Lloyd, K.O.
Analysis of melanoma cells stably transfected with b1,4GalNAc transferase (GM2/GD2 synthase) cDNA: relative glycosyltransferase levels play a dominant role in determining ganglioside expression
Arch. Biochem. Biophys.
323
11-18
1995
Homo sapiens (Q00973)
Furukawa, K.; Takamiya, K.; Furukawa, K.
beta1,4-N-acetylgalactosaminyltransferase-GM2/GD2 synthase: a key enzyme to control the synthesis of brain-enriched complex gangliosides
Biochim. Biophys. Acta
1573
356-362
2002
Homo sapiens (Q00973), Mus musculus (Q09200)
Daniotti, J.L.; Martina, J.A.; Giraudo, C.G.; Zurita, A.R.; Maccioni, H.J.F.
GM3 alpha2,8-sialyltransferase (GD3 synthase): protein characterization and sub-Golgi location in CHO-K1 cells
J. Neurochem.
74
1711-1720
2000
Homo sapiens
Li, J.; Rancour, D.M.; Allende, M.L.; Worth, C.A.; Darling, D.S.; Gilbert, J.B.; Menon, A.K.; Young, W.W., Jr.
The DXD motif is required for GM2 synthase activity but is not critical for nucleotide binding
Glycobiology
11
217-229
2001
Homo sapiens (Q00973)
Gotoh, M.; Sato, T.; Kiyohara, K.; Kameyama, A.; Kikuchi, N.; Kwon, Y.D.; Ishizuka, Y.; Iwai, T.; Nakanishi, H.; Narimatsu, H.
Molecular cloning and characterization of beta1,4-N-acetylgalactosaminyltransferases IV synthesizing N,N'-diacetyllactosediamine
FEBS Lett.
562
134-140
2004
Homo sapiens (Q76KP1)
Ramakrishnan, B.; Qasba, P.K.
Role of a single amino acid in the evolution of glycans of invertebrates and vertebrates
J. Mol. Biol.
365
570-576
2007
Drosophila melanogaster, Homo sapiens
Martinez, C.; Hofmann, T.J.; Marino, R.; Dominici, M.; Horwitz, E.M.
Human bone marrow mesenchymal stromal cells express the neural ganglioside GD2: a novel surface marker for the identification of MSCs
Blood
109
4245-4248
2007
Homo sapiens (Q00973), Homo sapiens
Wang, H.R.; Hsieh, C.Y.; Twu, Y.C.; Yu, L.C.
Expression of the human Sda beta-1,4-N-acetylgalactosaminyltransferase II gene is dependent on the promoter methylation status
Glycobiology
18
104-113
2008
Homo sapiens
Ootsuka, S.; Asami, S.; Sasaki, T.; Yoshida, Y.; Nemoto, N.; Shichino, H.; Chin, M.; Mugishima, H.; Suzuki, T.
Useful markers for detecting minimal residual disease in cases of neuroblastoma
Biol. Pharm. Bull.
31
1071-1074
2008
Homo sapiens
Prinetti, A.; Aureli, M.; Illuzzi, G.; Prioni, S.; Nocco, V.; Scandroglio, F.; Gagliano, N.; Tredici, G.; Rodriguez-Menendez, V.; Chigorno, V.; Sonnino, S.
GM3 synthase overexpression results in reduced cell motility and in caveolin-1 upregulation in human ovarian carcinoma cells
Glycobiology
20
62-77
2010
Homo sapiens
Chen, L.C.; Brown, A.B.; Cheung, I.Y.; Cheung, N.K.; Kris, M.G.; Krug, L.M.
Analysis of GD2/GM2 synthase mRNA as a biomarker for small cell lung cancer
Lung Cancer
67
216-220
2010
Homo sapiens
Song, N.; Kim, S.J.; Kwon, H.Y.; Son, S.W.; Kim, K.S.; Ahn, H.B.; Lee, Y.C.
Transcriptional activation of human GM3 synthase (hST3Gal V) gene by valproic acid in ARPE-19 human retinal pigment epithelial cells
BMB Rep.
44
405-409
2011
Homo sapiens
Miyata, M.; Ichihara, M.; Tajima, O.; Sobue, S.; Kambe, M.; Sugiura, K.; Furukawa, K.; Furukawa, K.
UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor alpha and interleukin 6
Biochem. Biophys. Res. Commun.
445
504-510
2014
Homo sapiens (Q00973)
Harlalka, G.V.; Lehman, A.; Chioza, B.; Baple, E.L.; Maroofian, R.; Cross, H.; Sreekantan-Nair, A.; Priestman, D.A.; Al-Turki, S.; McEntagart, M.E.; Proukakis, C.; Royle, L.; Kozak, R.P.; Bastaki, L.; Patton, M.; Wagner, K.; Coblentz, R.; Price, J.; Mezei, M.; Schlade-Bartusiak, K.; Platt, F.M.; Hurle, M.E.; Crosby, A.H.
Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis
Brain
136
3618-3624
2013
Homo sapiens (Q00973)
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