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Information on EC 2.4.1.150 - N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase and Organism(s) Mus musculus and UniProt Accession Q5JCT0
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2.4.1.150 N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferaseIUBMB Comments
The enzyme acts on poly-N-acetyllactosamine [glycan chains of beta-D-galactosyl-(1->4)-N-acetyl-D-glucosamine units connected by beta(1,3) linkages] attached to proteins or lipids. It transfers a GlcNAc residue by beta(1,6)-linkage to galactosyl residues close to non-reducing terminals, introducing a branching pattern known as I branching.
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Word Map
- 2.4.1.150
- cataract
- poly-n-acetyllactosamine
-
cryaa
- n-acetyllactosamine
-
polylactosamines
-
glycan-binding
- diagnostics
- pharmacology
- medicine
- synthesis
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
gcnt2, i-branching enzyme, glucosaminyl (n-acetyl) transferase 2, i-branching beta-1,6-n-acetylglucosaminyltransferase, i-branching n-acetylglucosaminyltransferase, i n-acetylglucosaminyltransferase, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acetylglucosaminyltransferase, uridine diphosphoacetylglucosamine-acetyllactosaminide beta1-->6-
-
-
-
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beta1-6GnT
-
-
-
-
Galbeta1-->4GlcNAc-R beta1-->6 N-acetylglucosaminyltransferase
-
-
-
-
I N-acetylglucosaminyltransferase
-
-
-
-
IGnT
N-acetylglucosaminyltransferase
-
-
-
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N-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferase
-
-
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UDP-GlcNAc:Gal-R, beta-D-6-N-acetylglucosaminyltransferase
-
-
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UDP-N-acetyl-D-glucosamine:beta-D-galactosyl-(1->4)-N-acetyl-D-glucosaminide 6-beta-N-acetyl-D-glucosaminyltransferase
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-
-
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uridine diphosphoacetylglucosamine-acetyllactosaminide beta1-->6-acetylglucosaminyltransferase
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-
-
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IGnT
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexosyl group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetyl-alpha-D-glucosamine:beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminide 6-beta-N-acetylglucosaminyltransferase (configuration-inverting)
The enzyme acts on poly-N-acetyllactosamine [glycan chains of beta-D-galactosyl-(1->4)-N-acetyl-D-glucosamine units connected by beta(1,3) linkages] attached to proteins or lipids. It transfers a GlcNAc residue by beta(1,6)-linkage to galactosyl residues close to non-reducing terminals, introducing a branching pattern known as I branching.
CAS REGISTRY NUMBER
COMMENTARY
85638-40-0
-
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-D-glucosamine + Galbeta(1-3)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-4)(Fucalpha(1-3))GlcNAcbeta(1-3)Galbeta(1-4)Glc
?
very poor substrate
-
-
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
UDP + Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)Glc
i.e. lacto-N-neotetraose, IGnT B forms branch in the internal Gal residue
no transfer to the terminal Gal residue
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
UDP + Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
UDP-N-acetyl-D-glucosamine + Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAc
UDP + Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAc
UDP-N-acetyl-D-glucosamine + GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
UDP + GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)Glc
UDP-N-acetyl-D-glucosamine + Galalpha(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
?
IGnT A: at 256% of the rate with lacto-N-neotetraose
-
-
?
UDP-N-acetyl-D-glucosamine + Galalpha(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
?
IGnT B: at 148% of the rate with lacto-N-neotetraose
-
-
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-3)GlcNAcbeta(1-3)Galbeta(1-4)Glc
?
poor substrate
-
-
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-3)GlcNAcbeta(1-3)Galbeta(1-4)Glc
?
IGnT B: at 6% of the rate with lacto-N-neotetraose
-
-
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-3)GlcNAcbeta(1-3)Galbeta(1-4)Glc
?
IGnT A: at 4% of the rate with lacto-N-neotetraose
-
-
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-3)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
?
poor substrate
-
-
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-3)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
?
IGnT B: at 10% of the rate with lacto-N-neotetraose
-
-
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-3)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
?
IGnT A: at 6% of the rate with lacto-N-neotetraose
-
-
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
UDP + Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
IGnT B: at 181% of the rate with lacto-N-neotetraose
IGnT B: major product, minor product is Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)Glc, IGnT B forms beta-1,6 branch in both of the internal galactosyl residues, prolonged incubation results in di-branched oligosaccharide
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
UDP + Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
IGnT A: at 170% of the rate with lacto-N-neotetraose
-
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
UDP + Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
i.e. para-lacto-N-neohexaose
-
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
UDP + Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
i.e. para-lacto-N-neohexaose
IGnT B: major product, minor product is Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)Glc, IGnT B forms beta-1,6 branch in both of the internal galactosyl residues, prolonged incubation results in di-branched oligosaccharide
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAc
UDP + Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAc
IGnT B: at 164% of the rate with lacto-N-neotetraose
-
-
?
UDP-N-acetyl-D-glucosamine + Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAc
UDP + Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAc
IGnT A: at 194% of the rate with lacto-N-neotetraose
-
-
?
UDP-N-acetyl-D-glucosamine + GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
UDP + GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)Glc
IGnT A: at 22% of the rate with lacto-N-neotetraose
only product
?
UDP-N-acetyl-D-glucosamine + GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
UDP + GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)(GlcNAcbeta(1-6))Galbeta(1-4)Glc
IGnT B: at 41% of the rate with lacto-N-neotetraose
only product
?
UDP-N-acetyl-D-glucosamine + NeuAcalpha(2-3)Galbeta(1-4)GlcNacbeta(1-3)Galbeta(1-4)Glc
?
IGnT B: at 123% of the rate with lacto-N-neotetraose
-
-
?
UDP-N-acetyl-D-glucosamine + NeuAcalpha(2-3)Galbeta(1-4)GlcNacbeta(1-3)Galbeta(1-4)Glc
?
IGnT A: at 35% of the rate with lacto-N-neotetraose
-
-
?
UDP-N-acetyl-D-glucosamine + NeuAcalpha(2-6)Galbeta(1-4)GlcNacbeta(1-3)Galbeta(1-4)Glc
?
IGnT A: at 256% of the rate with lacto-N-neotetraose
-
-
?
UDP-N-acetyl-D-glucosamine + NeuAcalpha(2-6)Galbeta(1-4)GlcNacbeta(1-3)Galbeta(1-4)Glc
?
IGnT B: at 148% of the rate with lacto-N-neotetraose
-
-
?
UDP-N-acetyl-D-glucosamine + poly-N-acetyllactosamine
?
-
forms branches in poly-N-acetyllactosamines
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-
?
UDP-N-acetyl-D-glucosamine + poly-N-acetyllactosamine
?
forms branches in poly-N-acetyllactosamines
-
-
?
UDP-N-acetyl-D-glucosamine + poly-N-acetyllactosamine
?
-
forms branches in poly-N-acetyllactosamines, which bear the I blood group antigen
-
-
?
UDP-N-acetyl-D-glucosamine + poly-N-acetyllactosamine
?
forms branches in poly-N-acetyllactosamines, which bear the I blood group antigen
-
-
?
additional information
?
-
-
2 isoforms IGnT A and IGnT B, C-terminal 1/4 of IGnT B is identical to that of IGnT A, the rest of the sequences shows 63% identity
-
-
?
additional information
?
-
2 isoforms IGnT A and IGnT B, C-terminal 1/4 of IGnT B is identical to that of IGnT A, the rest of the sequences shows 63% identity
-
-
?
additional information
?
-
2 isoforms IGnT A and IGnT B, C-terminal 1/4 of IGnT B is identical to that of IGnT A, the rest of the sequences shows 63% identity
-
-
?
additional information
?
-
generally, oligosaccharides with the Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc(Nac) sequence serve as good substrates, addition of Galalpha(1-3) or sialic acid alpha(2-6) to the non-reducing end gelactose enhances the acceptor activity, while sialic acid alpha2-3 linkage shows a repressive effect, no substrate: N-acetyl-beta-D-glucosaminyl-1,3-beta-D-galactosyl-1,4-beta-D-glucose
-
-
?
additional information
?
-
generally, oligosaccharides with the Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc(Nac) sequence serve as good substrates, addition of Galalpha(1-3) or sialic acid alpha(2-6) to the non-reducing end gelactose enhances the acceptor activity, while sialic acid alpha2-3 linkage shows a repressive effect, no substrate: N-acetyl-beta-D-glucosaminyl-1,3-beta-D-galactosyl-1,4-beta-D-glucose
-
-
?
additional information
?
-
-
a major enzyme involved in the branching of poly-N-acetyllactosamine chains in embryoglycan, branching of poly-N-acetyllactosamine chains is performed by beta1,6-N-acetylglucosaminylation of the galactosyl residue
-
-
?
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
additional information
?
-
-
a major enzyme involved in the branching of poly-N-acetyllactosamine chains in embryoglycan, branching of poly-N-acetyllactosamine chains is performed by beta1,6-N-acetylglucosaminylation of the galactosyl residue
-
-
?
UDP-N-acetyl-D-glucosamine + poly-N-acetyllactosamine
?
-
forms branches in poly-N-acetyllactosamines, which bear the I blood group antigen
-
-
?
UDP-N-acetyl-D-glucosamine + poly-N-acetyllactosamine
?
forms branches in poly-N-acetyllactosamines, which bear the I blood group antigen
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
talniflumate
inhibits GCNT3 and mucins in genetically engineered mice in vivo
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.55
Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)GlcNAcbeta(1-3)Galbeta(1-4)Glc
IGnT B
0.52
NeuAcalpha(2-6)Galbeta(1-4)GlcNacbeta(1-3)Galbeta(1-4)Glc
IGnT B
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
when expressed as proteins IGnT B shows higher specific activity than IGnT A
additional information
when expressed as proteins IGnT B shows higher specific activity than IGnT A
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
native and knockout mutants, mutant cells exhibited a reduced capability in embryoglycan synthesis and adhere weakly to laminin-coated plates
D-3 embryonic stem cells moderately express IGnT A and B
P-19 embryonal carcinoma cells moderately express IGnT A and B
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
core 2 beta-1,6-N-acetylglucosaminyltransferase (GCNT3) is a core mucin-synthesizing enzyme
malfunction
C2GnT2 deficiency, impair of mucosal barrier, increase of susceptibility to colitis, reduced immunoglobulin abundance, loss of all core 4 O-glycan biosynthetic activity
malfunction
in mouse pancreatic cancer tumors, GCNT3 upregulation is correlated with increased expression of mucins. Aberrant GCNT3 expression is associated with increased mucin production, aggressive tumorigenesis, and reduced survival. CRISPR-mediated knockout of GCNT3 in pancreatic cancer cells reduced proliferation and spheroid formation
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). GCNT3_MOUSE
437
1
50698
Swiss-Prot
Secretory Pathway (Reliability: 1)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
CRISPR-mediated knockout of GCNT3 in pancreatic cancer cells. A significant increase in pancreas weight is observed in Kras mice compared with wild-type mice. Only 6% of the pancreata from Kras mice are free from PanIN lesions and PDAC, whereas 100% of pancreata are normal in wild-type mice
additional information
-
mutation experiments at the GT boxes of the promoters of IGnT A and B genes
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
2 isoforms IGnT A and IGnT B are produced by alternative splicing of the IGnT gene, the C-terminal 1/4 of IGnT B is identical to that of IGnT A
expression of each isoform is controlled by a different promoter, characterization of the promoters: GT boxes play crucial roles in transcriptional regulation of the genes
-
IGnT A is cloned
IGnT B is cloned from mouse liver cDNA, nucleotide and amino acid sequence, exon organization of the IGnT gene, expression of IGnT A and B in COS-7 and CHO cells
2 isoforms IGnT A and IGnT B are produced by alternative splicing of the IGnT gene, the C-terminal 1/4 of IGnT B is identical to that of IGnT A
-
2 isoforms IGnT A and IGnT B are produced by alternative splicing of the IGnT gene, the C-terminal 1/4 of IGnT B is identical to that of IGnT A
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
in mouse pancreatic cancer tumors, GCNT3 upregulation (103fold) is correlated with increased expression of mucins (5 to 87fold). Pancreata from 6-week-old Kras mice treated with talniflumate for 1 week show a significant decrease in GCNT3 and mucin expression in PanIN lesions. Further, GCNT3 protein expression is significantly decreased in the pancreas of talniflumate-treated Kras mice compared with untreated control mouse pancreas. mRNA expression of GCNT3 is also observed to be lower in pancreatic tissues from talniflumate-treated mice
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Chen, G.Y.; Kurosawa, N.; Muramatsu, T.
Functional analysis of promoter activity of murine beta-1,6-N-acetylglucosaminyltransferase
Gene
275
253-259
2001
Mus musculus
Chen, G.Y.; Kurosawa, N.; Muramatsu, T.
A novel variant form of murine beta-1,6-N-acetylglucosaminyltransferase forming branches in poly-N-acetyllactosamines
Glycobiology
10
1001-1011
2000
Mus musculus (A2IQH4), Mus musculus (A2IQH5)
Fukuda, M.
beta6-N-acetylglucosaminyltransferase (IGnT)
Handbook of Glycosyltransferases and Related Genes
2002
125-132
2002
Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
-
Li, C.; Wu, Q.
Adaptive evolution of multiple-variable exons and structural diversity of drug-metabolizing enzymes
BMC Evol. Biol.
7
69
2007
Canis lupus familiaris, Danio rerio, Gallus gallus, Homo sapiens, Macaca mulatta, Monodelphis domestica, Mus musculus, Pan troglodytes, Rattus norvegicus, Xenopus tropicalis
Muramatsu, H.; Kusano, T.; Sato, M.; Oda, Y.; Kobori, K.; Muramatsu, T.
Embryonic stem cells deficient in I beta1,6-N-acetylglucosaminyltransferase exhibit reduced expression of embryoglycan and the loss of a Lewis X antigen, 4C9
Glycobiology
18
242-249
2008
Mus musculus
Stone, E.L.; Ismail, M.N.; Lee, S.H.; Luu, Y.; Ramirez, K.; Haslam, S.M.; Ho, S.B.; Dell, A.; Fukuda, M.; Marth, J.D.
Glycosyltransferase function in core 2-type protein O glycosylation
Mol. Cell. Biol.
29
3770-3782
2009
Mus musculus (Q5JCT0)
Rao, C.V.; Janakiram, N.B.; Madka, V.; Kumar, G.; Scott, E.J.; Pathuri, G.; Bryant, T.; Kutche, H.; Zhang, Y.; Biddick, L.; Gali, H.; Zhao, Y.D.; Lightfoot, S.; Mohammed, A.
Small-molecule inhibition of GCNT3 disrupts mucin biosynthesis and malignant cellular behaviors in pancreatic cancer
Cancer Res.
76
1965-1974
2016
Homo sapiens (O95395), Mus musculus (Q5JCT0), Mus musculus C5BL/6 (Q5JCT0)
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