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Information on EC 2.4.1.228 - lactosylceramide 4-alpha-galactosyltransferase
for references in articles please use BRENDA:EC2.4.1.228
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EC Tree 2 Transferases
2.4 Glycosyltransferases
2.4.1 Hexosyltransferases
2.4.1.228 lactosylceramide 4-alpha-galactosyltransferase
IUBMB Comments
For explanation of superscript II in systematic name, see 2-carb.37.
The enzyme appears in viruses and cellular organisms
- 2.4.1.228
- glycosphingolipids
- sphingolipids
- gangliosides
- lysosomal
- gaucher
- sphingomyelin
- glycolipids
-
multidrug
-
glccer
- sphingomyelinase
- sphingosine
- p-glycoprotein
- gm3
- d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol
- glucocerebrosidase
- eliglustat
-
d-pdmp
- niemann-pick
-
ceramide-induced
-
iminosugars
- fabry
- ceramidase
- glucosylceramidase
-
shiga
-
nb-dnj
- c6-ceramide
- fumonisin
-
globo-series
- dihydroceramide
- 1-phenyl-2-decanoylamino-3-morpholino-1-propanol
- n-butyldeoxynojirimycin
- gd1a
-
verotoxins
-
neuronopathic
- medicine
Reaction Schemes
showSynonyms
glucosylceramide synthase, a4galt, gb3/cd77 synthase, gb3 synthase, alpha1,4-galactosyltransferase, alpha1,4gal-t, gb3 galactosyltransferase, globotriaosylceramide synthase, gb3cer synthase, pk synthase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
A4GalT
alpha 1-4 galactosyltransferase
-
-
-
-
alpha1,4-galactosyltransferase
Gal-beta1-4Glcbeta1-Cer alpha1,4-galactosyltransferase
-
-
-
-
galactosyltransferase, uridine diphosphogalactose-lactosylceramide
-
-
-
-
galactosyltransferase, uridine diphosphogalactose-lactosylceramide alpha1-4-
-
-
-
-
Gb3 galactosyltransferase
-
-
-
-
GB3 synthase
Gb3/CD77 synthase
globotriaosylceramide synthase
globotriaosylceramide/CD77 synthase
-
-
-
-
histo-blood group Pk antigen synthase
-
-
-
-
histo-blood group Pk UDP-galactose
-
-
-
-
lactosylceramide alpha1,4galactosyltransferase
-
-
-
-
UDP-galactose-lactosylceramide galactosyltransferase
-
-
-
-
UDP-galactose:beta-D-galactosyl-beta-1-R 4-alpha-D-galactosyltransferase
-
-
-
-
UDP-galactose:lactosylceramide alpha-galactosyltransferase
-
-
-
-
UDP-galactose:lactosylceramide alpha1-4-galactosyltransferase
-
-
-
-
GB3 synthase
-
-
-
-
globotriaosylceramide synthase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
UDP-alpha-D-galactose + beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide = UDP + alpha-D-galactosyl-(1->4)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
galactosyl group transfer
galactosyl group transfer
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
KEGG
MetaCyc
globo-series glycosphingolipids biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
UDP-galactose:beta-D-galactosyl-(1->4)-D-glucosyl-(1<->1)-ceramide 4II-alpha-D-galactosyltransferase
For explanation of superscript II in systematic name, see {iupac/2carb/37#372::2-carb.37}.
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CAS REGISTRY NUMBER
COMMENTARY
52725-57-2
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
UDP-Gal + Galbeta1,4Glc-PAA
UDP + ?
Substrates: i.e. Lac-PAA, precursor to Pk
Products: -
Products: -
?
UDP-Gal + Galbeta1,4GlcNAc-R1
UDP + Galalpha1,4Galbeta1,4GlcNAc-R1
Substrates: acceptor substrate is a nonasaccharide azide with two terminal lactosamine units
Products: -
Products: -
?
UDP-Gal + Galbeta1,4GlcNAc-R2
UDP + Galalpha1,4Galbeta1,4GlcNAc-R2
Substrates: acceptor substrate is a decasaccharide azide with two terminal lactosamine units
Products: -
Products: -
?
UDP-Gal + Galbeta1,4GlcNAc-R3
UDP + Galalpha1,4Galbeta1,4GlcNAc-R3
Substrates: acceptor substrate is a dodecasaccharide azide with two terminal lactosamine units
Products: -
Products: -
?
UDP-Gal + Galbeta1,4GlcNAcbeta1,3Galbeta1,4Glc-PAA
UDP + ?
Substrates: i.e. nLc4-PAA, precursor to P1
Products: -
Products: -
?
UDP-Gal + GalNAcbeta1,3Galalpha1,4Galbeta1,4Glc-PAA
UDP + ?
Substrates: i.e. Gbeta4-PAA, precursor to NOR1
Products: -
Products: -
?
UDP-Gal + saposin D glycopeptide
UDP + Galalpha1,4-saposin D glycopeptide
Substrates: acceptor is a synthetic human saposin D 1-35 aa. glycopeptide hydrazide
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1,4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1,4)-beta-D-galactosyl-(1,4)-D-glucosylceramide
-
Substrates: -
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1,4)-N-acetyl-beta-D-glucosaminyl-alpha-D-galactosyl-(1,4)-beta-D-glucosylceramide
UDP + alpha-D-galactosyl-(1,4)-beta-D-galactosyl-(1,4)-N-acetyl-beta-D-glucosaminyl-alpha-D-galactosyl-(1,4)-beta-D-glucosylceramide
-
Substrates: P1 antigen synthesis
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
-
Substrates: -
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
Substrates: -
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
Substrates: -
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
Substrates: -
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
Substrates: -
Products: -
Products: -
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
Substrates: -
Products: -
Products: -
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
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Substrates: UDP-galactose is the sole sugar donor
Products: -
Products: -
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
Substrates: reduction of enzyme activity following retinoic acid induced differentiation
Products: -
Products: -
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
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Substrates: in the small p cells in vitro only
Products: -
Products: -
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
Substrates: -
Products: -
Products: -
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
Substrates: -
Products: -
Products: -
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
Substrates: UDP-galactose is the sole sugar donor
Products: -
Products: -
?
additional information
?
-
-
Substrates: globotriaosylceramide, Gb3, is synthesized from lactosylceramide by alpha1,4-galactosyltransferase Gb3/CD77 synthase
Products: -
Products: -
?
additional information
?
-
Substrates: the consensus enzyme synthesizes both the Pk and P1 antigens, while its p.Q211E variant additionally synthesizes the NOR antigen
Products: -
Products: -
?
additional information
?
-
-
Substrates: the consensus enzyme synthesizes both the Pk and P1 antigens, while its p.Q211E variant additionally synthesizes the NOR antigen
Products: -
Products: -
?
additional information
?
-
Substrates: both wild-type and mutant Q211E produce P1 glycotopes on N-glycoproteins that are recognized by Stx1 but not Stx2 B receptor subunits
Products: -
Products: -
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additional information
?
-
-
Substrates: targeted disruption of Gb3/CD77 synthase gene results in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins
Products: -
Products: -
?
additional information
?
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Substrates: no substrates: galactosylceramide, glucosylceramide, neolactotetraose, neolactotetraosylceramide
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
UDP-galactose + beta-D-galactosyl-(1,4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1,4)-beta-D-galactosyl-(1,4)-D-glucosylceramide
-
Substrates: -
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1,4)-N-acetyl-beta-D-glucosaminyl-alpha-D-galactosyl-(1,4)-beta-D-glucosylceramide
UDP + alpha-D-galactosyl-(1,4)-beta-D-galactosyl-(1,4)-N-acetyl-beta-D-glucosaminyl-alpha-D-galactosyl-(1,4)-beta-D-glucosylceramide
-
Substrates: P1 antigen synthesis
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
Substrates: -
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
-
Substrates: -
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
Substrates: -
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
Substrates: -
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
Substrates: -
Products: -
Products: -
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: globotriaosylceramide, Gb3, is synthesized from lactosylceramide by alpha1,4-galactosyltransferase Gb3/CD77 synthase
Products: -
Products: -
?
additional information
?
-
-
Substrates: targeted disruption of Gb3/CD77 synthase gene results in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mn2+
Mn2+
-
a second divalent cation in the enzyme assay can inhibit the enzyme activity
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-deoxy-D-glucose
-
inhibits the Gb3S promoter activity in dose dependent manner
DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol
-
i.e. PPMP, a glycosphingolipid synthesis inhibitor
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
tumour stress activation of glucosylceramide synthase
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
cloned enzyme encodes exclusive Pk alpha-4-galactosyltransferase activity
additional information
-
cloned enzyme encodes exclusive Pk alpha-4-galactosyltransferase activity
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
leukaemia-myeloid cell lines: K562, KG-1, HL-60, and THP-1, lymphoma-lymphoid cell lines: Reh, Daudi, Raji, RPMI 8226, CCRF-CEM, and MOLT-4
-
-
brenda
NTERA-2 cl.D1 cells, a cloned EC subline of the teratocarcinoma cell line TERA-2, during retinoic acid induced differentiation, Burkitt lymphoma Ramos cells
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
low, but definite, levels of Gb3/CD77 are expressed in the microvascular endothelial cells of the brain cortex
brenda
globo series-related genes, and in particular, A4GALT, are elevated in epithelial cancer cells and associated with improved patient's outcome
brenda
-
blood of a small p subject and a P1 control subject
brenda
additional information
-
THP-1, RPMI 8226, Daudi, and Raji cell lines with detectable enzyme activity, no detectable enzyme activity: K562, KG-1, HL-60, Reh, MOLT-4, CCRF-CEM cell lines
brenda
-
lower enzyme level in P2-type erythrocytes, high enzyme level in P1-type erythrocytes, no enzyme activity in p-erythrocytes
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
additional information
malfunction
-
the inhibitory effect of 1-deoxygalactonojirimycin on alpha-galactosidase A activity causes Gb3 accumulation in G3S/COS-7 cells. Fabry disease is a lysosomal storage disorder caused by an alpha-galactosidase A deficiency and resulting in the accumulation of glycosphingolipids, predominantly globotriaosylceramide
malfunction
-
overexpression of the truncated form of N-methyl-D-asparate-associated protein 1, GRINA-C, and some members of the full-length TMBIM family, including FAS inhibitory molecule 2, reduces Gb3, leading to accumulation of lactosylceramide. The change of glycolipid composition is restored by overexpression of Gb3 synthase, although the mRNA level of Gb3 synthase is unchanged. GRINA-C is associated with Gb3 synthase. Reduction of only the mature form of Gb3 synthase by the expression of GRINA-C is restored by addition of lysosome inhibitors, reduction of Gb3 synthase after overexpression through increased lysosomal degenaration. Phenotypes, overview
malfunction
-
effect of GCS inhibitor DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol and multidrug resistance 1/P-glycoprotein, MDR1, pump inhibitor cyclosporin A on expression and cisplatin cytotoxicity. Enzyme inhibition potentiates cisplatin cytotoxicity in H1299 cells and abolishes cell surface globotriaosylceramide (Gb3) expression of resistant cells
malfunction
habitual abortion in a Chinese woman is caused by the synonymous 903C>G mutation in the A4GALT gene. The synonymous mutation of 903C>G in the A4GALT gene causes the p phenotype in P1Pk blood system and it is the in vivo anti-PP1Pk antibody of the patient that causes habitual abortion
malfunction
deletion of A4GALT significantly increases the number of extravasated cells and more clusters are formed as compared with parental cells. The deletion of A4GALT leads to increased cell motility and invasiveness in vitro as well as in vivo, features commonly accompanied with epithelial-to-mesenchymal transition
metabolism
single nucleotide polymorphisms in A4GALT spur extra products of the human Gb3/CD77 synthase and underlie the P1PK blood group system
metabolism
the enzyme is responsible for biosynthesis of Gal(alpha1-4)Gal moiety in Gb3 (CD77, Pk antigen) and P1 glycosphingolipids
physiological function
-
globotriaosylceramide, Gb3, synthesized from lactosylceramide by alpha1,4-galactosyltransferase Gb3/CD77 synthase, is a well known receptor for Shiga toxin, Stx, produced by enterohemorrhagic Escherichia coli and Shigella dysenteriae
physiological function
the enzyme is involved in the biosynthesis of unique globoside (Gb4Cer) derivatives, NOR1, NORint, and NOR2, in which Gal(alpha1-4), GalNAc(beta1-3)Gal(alpha1-4), and Gal(alpha1-4)GalNAc(beta1-3)Gal(alpha1-4), respectively, are linked to the terminal GalNAc residue of Gb4Cer, transfer of Gal to GalNAc, overview
physiological function
the enzyme catalyzes the synthesis of Gal(alpha1-4)Gal moiety in globotriaosylceramide (Gb3Cer, CD77, Pk blood group antigen), a glycosphingolipid of the globo series
physiological function
-
Ceramide increases in response to chemotherapy, leading to proliferation arrest and apoptosis. A tumour stress activation of glucosylceramide synthase follows to eliminate ceramide by formation of glycosphingolipids (GSLs) such as globotriaosylceramide (Gb3), the functional receptor of verotoxin-1
physiological function
the A4GALT gene encodes the alpha1-4 galactosyltransferase, a key enzyme responsible for synthesis of globoside glycosphingolipids. Globo series-related genes, and in particular, A4GALT, are elevated in epithelial cancer cells and associated with improved patient's outcome
additional information
-
overexpression of Gb3 synthase in transgenic TgG3S mice, phenotype, overview. Age-related increase in the kidney Gb3 content in TgG3S(+/-)M(+/-)/KO mice, while neither the Gb3 content in the heart nor the alpha-galactosidase A activity in the heart or kidney change during this time
additional information
the naturally occuring mutation Q211E enables the Gb3/CD77 synthase mutant to synthesize unique globoside (Gb4Cer) NOR derivatives, overview. The NOR antigen appears as a result of the C631G mutation in the gene encoding Gb3/CD77 synthase. Expression of NOR antigen is correlated with expression of the P1 antigen
additional information
-
the naturally occuring mutation Q211E enables the Gb3/CD77 synthase mutant to synthesize unique globoside (Gb4Cer) NOR derivatives, overview. The NOR antigen appears as a result of the C631G mutation in the gene encoding Gb3/CD77 synthase. Expression of NOR antigen is correlated with expression of the P1 antigen
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22000
-
alpha 1 * 65000 + beta 1 * 22000, linked through a disulfide bond, SDS-PAGE
37500
x * 37500, recombinant c-Myc- and His6-tagged fragment A4GALT(130-1059), SDS-PAGE
65000
-
alpha 1 * 65000 + beta 1 * 22000, linked through a disulfide bond, SDS-PAGE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
alpha 1 * 65000 + beta 1 * 22000, linked through a disulfide bond, SDS-PAGE
?
x * 37500, recombinant c-Myc- and His6-tagged fragment A4GALT(130-1059), SDS-PAGE
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
Gb3/CD77 synthase contains two used N-glycosylation sites at positions N121 and N203. The N-glycan at N203 is essential for activity and correct subcellular localization. The N-glycan at N121 is dispensable and its absence even increases the activity of the enzyme. The glycoform missing the N121 glycan correctly localizes in the Golgi, whereas a glycoform without the N203 site partially mislocalises in the endoplasmic reticulum. A double mutant missing both N-glycans is inactive and accumulates in the endoplasmic reticulum
glycoprotein
glycovariants devoid of N-glycan at position N203 or simultaneously at N121 and N203 sites lack enzymatic activity. The presence of both N-glycans is required for efficient secretion of the enzyme. The fully N-glycosylated enzyme contains one complex and one hybrid/oligomannose N-glycan, while single mutants contain only the complex type
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Q211E
S123A
S123A/Q211E
S123A/T205A
S123A/T205A/Q211E
T205A
T205A/Q211E
Q211E
naturally occuring mutation enabeling the mutant to synthesize unique globoside (Gb4Cer) NOR derivatives, overview
Q211E
a mutation in the open reading frame, which broadens the enzyme specificity, making it able also to synthesize Gal(alpha1-4)GalNAc moiety, which constitutes the defining terminal disaccharide of the NOR antigen (carried by two glycosphingolipids: NOR1 and NOR2)
Q211E
the mutation broadens the enzyme acceptor specificity, so the enzyme can not only attach galactose to another galactose but also to N-acetylgalactosamine. The latter reaction leads to synthesis of NOR antigens, which are glycosphingolipids with terminal Gal(alpha1-4)GalNAc sequence. Cells transfected with vectors encoding Gb3/CD77 synthase with substitutions p. Q211D or p. Q211N do not express Pk, P1 and NOR antigens, suggesting complete loss of enzymatic activity. Thus, amino acid residue at position 211 of Gb3/CD77 synthase is critical for specificity and activity of the enzyme involved in formation of Pk, P1 and NOR antigens
S123A
mutant lacks one glycosylation site, shows partly increased activity
S123A/T205A
mutant lacks both glycosylation sites, is inactive and accumulates in the endoplasmic reticulum
S123A/T205A/Q211E
mutant lacks both glycosylation sites, is inactive and accumulates in the endoplasmic reticulum
T205A
mutant lacks one glycosylation site, shows reduced activity and partially mislocalises in the endoplasmic reticulum
T205A/Q211E
mutant lacks one glycosylation site, shows reduced activity and partially mislocalises in the endoplasmic reticulum
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, in 20% glycerol, stored at a concentration greater than 0.1 mg/ml without detectable loss of activity upon repeated freezing and thawing for 3 months
-
-70°C, however enzyme activity in RPMI 8226 cells destroyed by storage at -70°C
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant c-Myc- and His6-tagged fragment A4GALT(130-1059) from Spodoptera frugiperda Sf9 cells by nickel affinity chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA sequence determination and analysis, functional expression in L-VTR1 cells, the recombinant cells produce high levels of P1 antigen in the cytoplasm with a small amount on the cell surface, expression as fusion protein with protein A secreted to the cell culture medium
-
expression of Gb3 synthase in transgenic TgG3S mice, and overexpression in COS-7 cells
-
gene A4GALT, a fragment of the A4GALT gene spanning nucleotides 130-1059 of the open reading frame with C or G at position 631 respectively, is cloned in-frame with c-myc and hexahistidine tags and recombinantly expressed in Spodoptera frugiperda Sf9 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
10 mM 2-deoxy-D-glucose markedly reduces endogenous globotriaosylceramide synthase mRNA levels, can control globotriaosylceramide biosynthesis through the inhibition of globotriaosylceramide synthase transcription
-
globo series-related genes, and in particular, A4GALT, are elevated in epithelial cancer cells and associated with improved patient's outcome
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
verotoxin induces endothelial cell death via the verotoxin receptor globotriaosylceramide, Gb3/CD77, leading to hemolytic uremic syndrome
medicine
infections caused by Shiga toxin-producing Escherichia coli result in diarrhea, bloody diarrhea, and the hemolytic uremic syndrom, thus, it is important to better understand the pathways of intracellular transport of the toxin and to develop preventive and therapeutic measures for Shiga toxin-mediated diseases
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Taniguchi, N.; Yanagisawa, K.; Makita, A.; Naiki, M.
Purification and properties of rat liver globotriaosylceramide synthase, UDP-galactose:lactosylceramide alpha1-4-galactosyltransferase
J. Biol. Chem.
260
4908-4913
1985
Rattus norvegicus
brenda
Bailly, P.; Piller, F.; Cartron, J.P.; Leroy, Y.; Fournet, B.
Identification of UDP-galactose:lactose (lactosylceramide) alpha-4 and beta-3 galactosyltransferases in human kidney
Biochem. Biophys. Res. Commun.
141
84-91
1986
Homo sapiens
brenda
Iizuka, S.; Chen, S.H.; Yoshida, A.
Studies on the human blood group P system: an existence of UDP-Gal: lactosylceramide alpha 1 -> 4 galactosyltransferase in the small p type cells
Biochem. Biophys. Res. Commun.
137
1187-1195
1986
Homo sapiens
brenda
Chen, C.; Fenderson, B.A.; Andrews, P.W.; Hakomori, S.
Glycolipid glycosyltransferases in human embryonal carcinoma cells during retinoic acid induced differentiation
Biochemistry
28
2229-2238
1989
Homo sapiens
brenda
Stults, C.L.M.; Larsen, R.D.; Macher, B.A.
alpha-1,4Galactosyltransferase activity and Gbeta3Cer expression in human leukemia/lymphoma cell lines
Glycoconj. J.
12
680-689
1995
Homo sapiens
brenda
Mobassaleh, M.; Koul, O.; Mishra, K.; McCluer, R.H.; Keusch, G.T.
Developmentally regulated Gb3 galactosyltransferase and alpha-galactosidase determine Shiga toxin receptors in intestine
Am. J. Physiol.
267
G618-G624
1994
Oryctolagus cuniculus
brenda
Kojima, Y.; Fukumoto, S.; Furukawa, K.; Okajima, T.; Wiels, J.; Yokoyama, K.; Suzuki, Y.; Urano, T.; Ohta, M.; Furukawa, K.
Molecular cloning of globotriaosylceramide/CD77 synthase, a glycosyltransferase that initiates the synthesis of Globo series glycosphingolipids
J. Biol. Chem.
275
15152-15156
2000
Homo sapiens
brenda
Steffensen, R.; Carlier, K.; Wiels, J.; Levery, S.B.; Stroud, M.; Cedergren, B.; Sojka, B.N.; Bennett, E.P.; Jersild, C.; Clausen, H.
Cloning and expression of the histo-blood group Pk UDP-galactose: Galbeta1-4Glcbeta1-Cer alpha1,4-galactosyltransferase. Molecular genetic basis of the p phenotype
J. Biol. Chem.
275
16723-16729
2000
Homo sapiens (Q9NPC4), Homo sapiens
brenda
Iwamura, K.; Furukawa, K.; Uchikawa, M.; Sojka, B.N.; Kojima, Y.; Wiels, J.; Shiku, H.; Urano, T.; Furukawa, K.
The blood group P1 synthase gene is identical to the Gb3/CD77 synthase gene: a clue to the solution of the P1/P2/p puzzle
J. Biol. Chem.
278
44429-44438
2003
Homo sapiens
brenda
Okuda, T.; Tokuda, N.; Numata, S.; Ito, M.; Ohta, M.; Kawamura, K.; Wiels, J.; Urano, T.; Tajima, O.; Furukawa, K.; Furukawa, K.
Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins
J. Biol. Chem.
281
10230-10235
2006
Mus musculus
brenda
Okuda, T.; Nakayama, K.I.
Identification and characterization of the human Gb3/CD77 synthase gene promoter
Glycobiology
18
1028-1035
2008
Homo sapiens
brenda
Schweppe, C.H.; Bielaszewska, M.; Pohlentz, G.; Friedrich, A.W.; Buentemeyer, H.; Alexander Schmidt, M.; Kim, K.S.; Peter-Katalini?, J.; Karch, H.; Muething, J.
Glycosphingolipids in vascular endothelial cells: relationship of heterogeneity in Gb3Cer/CD77 receptor expression with differential Shiga toxin 1 cytotoxicity
Glycoconj. J.
25
291-304
2008
Homo sapiens (Q9NPC4), Homo sapiens
brenda
Shin, I.S.; Ishii, S.; Shin, J.S.; Sung, K.I.; Park, B.S.; Jang, H.Y.; Kim, B.W.
Globotriaosylceramide (Gb3) content in HeLa cells is correlated to Shiga toxin-induced cytotoxicity and Gb3 synthase expression
BMB Rep.
42
310-314
2009
Homo sapiens
brenda
Okuda, T.; Furukawa, K.; Nakayama, K.
A novel, promoter-based, target-specific assay identifies 2-deoxy-D-glucose as an inhibitor of globotriaosylceramide biosynthesis
FEBS J.
276
5191-5202
2009
Homo sapiens
brenda
Ramkumar, S.; Sakac, D.; Binnington, B.; Branch, D.R.; Lingwood, C.A.
Induction of HIV-1 resistance: cell susceptibility to infection is an inverse function of globotriaosyl ceramide levels
Glycobiology
19
76-82
2009
Homo sapiens
brenda
Shiozuka, C.; Taguchi, A.; Matsuda, J.; Noguchi, Y.; Kunieda, T.; Uchio-Yamada, K.; Yoshioka, H.; Hamanaka, R.; Yano, S.; Yokoyama, S.; Mannen, K.; Kulkarni, A.B.; Furukawa, K.; Ishii, S.
Increased globotriaosylceramide levels in a transgenic mouse expressing human alpha1,4-galactosyltransferase and a mouse model for treating Fabry disease
J. Biochem.
149
161-170
2011
Homo sapiens
brenda
Yamaji, T.; Nishikawa, K.; Hanada, K.
Transmembrane BAX inhibitor motif containing (TMBIM) family proteins perturbs a trans-Golgi network enzyme, Gb3 synthase, and reduces Gb3 biosynthesis
J. Biol. Chem.
285
35505-35518
2010
Homo sapiens
brenda
Suchanowska, A.; Kaczmarek, R.; Duk, M.; Lukasiewicz, J.; Smolarek, D.; Majorczyk, E.; Jaskiewicz, E.; Laskowska, A.; Wasniowska, K.; Grodecka, M.; Lisowska, E.; Czerwinski, M.
A single point mutation in the gene encoding Gb3/CD77 synthase causes a rare inherited polyagglutination syndrome
J. Biol. Chem.
287
38220-38230
2012
Homo sapiens (Q9NPC4), Homo sapiens
brenda
Kaczmarek, R.; Duk, M.; Szymczak, K.; Korchagina, E.; Tyborowska, J.; Mikolajczyk, K.; Bovin, N.; Szewczyk, B.; Jaskiewicz, E.; Czerwinski, M.
Human Gb3/CD77 synthase reveals specificity toward two or four different acceptors depending on amino acid at position 211, creating Pk, P1 and NOR blood group antigens
Biochem. Biophys. Res. Commun.
470
168-174
2016
Homo sapiens (Q9NPC4), Homo sapiens
brenda
Tyler, A.; Johansson, A.; Karlsson, T.; Gudey, S.K.; Braennstroem, T.; Grankvist, K.; Behnam-Motlagh, P.
Targeting glucosylceramide synthase induction of cell surface globotriaosylceramide (Gb3) in acquired cisplatin-resistance of lung cancer and malignant pleural mesothelioma cells
Exp. Cell Res.
336
23-32
2015
Homo sapiens
brenda
Jacob, F.; Alam, S.; Konantz, M.; Liang, C.Y.; Kohler, R.S.; Everest-Dass, A.V.; Huang, Y.L.; Rimmer, N.; Fedier, A.; Schoetzau, A.; Lopez, M.N.; Packer, N.H.; Lengerke, C.; Heinzelmann-Schwarz, V.
Transition of mesenchymal and epithelial cancer cells depends on alpha1-4 galactosyltransferase-mediated glycosphingolipids
Cancer Res.
78
2952-2965
2018
Homo sapiens (Q9NPC4)
brenda
Kaczmarek, R.; Mikolajewicz, K.; Szymczak, K.; Duk, M.; Majorczyk, E.; Krop-Watorek, A.; Buczkowska, A.; Czerwinski, M.
Evaluation of an amino acid residue critical for the specificity and activity of human Gb3/CD77 synthase
Glycoconj. J.
33
963-973
2016
Homo sapiens (Q9NPC4), Homo sapiens
brenda
Lv, X.; Chen, Y.; Luo, Y.; Li, L.; Wang, H.
The synonymous 903C>G mutation in the alpha 1,4-galactosyltransferase gene in a Chinese woman with habitual abortion A case report
Medicine (Baltimore)
98
e16361
2019
Homo sapiens (Q9NPC4), Homo sapiens
brenda
Kaczmarek, R.; Szymczak-Kulus, K.; Bereznicka, A.; Mikolajczyk, K.; Duk, M.; Majorczyk, E.; Krop-Watorek, A.; Klausa, E.; Skowronska, J.; Michalewska, B.; Brojer, E.; Czerwinski, M.
Single nucleotide polymorphisms in A4GALT spur extra products of the human Gb3/CD77 synthase and underlie the P1PK blood group system
PLoS ONE
13
e0196627
2018
Homo sapiens (Q9NPC4), Homo sapiens
brenda
Mikolajczyk, K.; Sikora, M.; Hanus, C.; Kaczmarek, R.; Czerwinski, M.
One of the two N-glycans on the human Gb3/CD77 synthase is essential for its activity and allosterically regulates its function
Biochem. Biophys. Res. Commun.
617
36-41
2022
Homo sapiens (Q9NPC4)
brenda
Szymczak-Kulus, K.; Czerwinski, M.; Kaczmarek, R.
Human Gb3/CD77 synthase a glycosyltransferase at the crossroads of immunohematology, toxicology, and cancer research
Cell. Mol. Biol. Lett.
29
137
2024
Homo sapiens (Q9NPC4)
brenda
Mikolajczyk, K.; Bereznicka, A.; Szymczak-Kulus, K.; Haczkiewicz-Lesniak, K.; Szulc, B.; Olczak, M.; Rossowska, J.; Majorczyk, E.; Kapczynska, K.; Bovin, N.; Lisowska, M.; Kaczmarek, R.; Miazek, A.; Czerwinski, M.
Missing the sweet spot one of the two N-glycans on human Gb3/CD77 synthase is expendable
Glycobiology
31
1145-1162
2021
Homo sapiens (Q9NPC4)
brenda
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