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Information on EC 2.4.1.274 - glucosylceramide beta-1,4-galactosyltransferase
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2.4.1.274 glucosylceramide beta-1,4-galactosyltransferaseIUBMB Comments
Involved in the synthesis of several different major classes of glycosphingolipids.
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Word Map
The enzyme appears in viruses and cellular organisms
Reaction Schemes
Synonyms
B4GalT5, B4GalT6, beta-1,4-galactosyltransferase V, beta-1,4-GalT-V, beta4-galactosyltransferase 5, beta4GalT5, Lac-Cer synthase, LacCer synthase, lactosylceramide synthase, UDP-Ga1:glucosylceramide beta1->4galactosyltransferase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
B4GalT5
B4GalT6
LacCer synthase
lactosylceramide synthase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
UDP-alpha-D-galactose + beta-D-glucosyl-(1<->1)-ceramide = UDP + beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide
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-
-
-
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
UDP-galactose:beta-D-glucosyl-(1<->1)-ceramide beta-1,4-galactosyltransferase
Involved in the synthesis of several different major classes of glycosphingolipids.
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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-galactose + beta-D-glucosyl-(1<->1)-ceramide
UDP + beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide
UDP-galactose + GlcNAc-beta-(1->3)-Gal-beta-(1->4)-Glc-beta-(1<->1)-Cer
?
-
-
-
-
?
UDP-galactose + beta-D-glucosyl-(1<->1)-ceramide
UDP + beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide
-
-
-
-
?
UDP-galactose + beta-D-glucosyl-(1<->1)-ceramide
UDP + beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide
-
the enzyme is involved in the synthesis of several different major classes of glycosphingolipids
-
-
?
UDP-galactose + beta-D-glucosyl-(1<->1)-ceramide
UDP + beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide
-
-
-
-
?
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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-galactose + beta-D-glucosyl-(1<->1)-ceramide
UDP + beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide
UDP-galactose + beta-D-glucosyl-(1<->1)-ceramide
UDP + beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide
-
the enzyme is involved in the synthesis of several different major classes of glycosphingolipids
-
-
?
UDP-galactose + beta-D-glucosyl-(1<->1)-ceramide
UDP + beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide
-
-
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
the enzyme is activated by Mn2+ and to a lesser extent by Mg2+ and Ca2+
Mg2+
Mn2+
Mg2+
-
the enzyme is inactive without added metal ions. Maximal activity is obtained in the presence of 1.0 mM Mn2+/Mg2+ (1:1)
Mg2+
-
the enzyme is activated by Mn2+ and to a lesser extent by Mg2+ and Ca2+
Mn2+
-
the enzyme is activated by Mn2+ and to a lesser extent by Mg2+ and Ca2+
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Cutscum
-
maximal activity in a detergent mixture, Triton X-100/Cutscum (1:2, v/v), 0.1 mg/ml
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Triton X-100
-
maximal activity in a detergent mixture, Triton X-100/Cutscum (1:2, v/v), 0.1 mg/ml
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Astrocytoma
Over-expression of beta-1,4-galactosyltransferase V increases the growth of astrocytoma cell line.
Atherosclerosis
Platelet derived growth factor recruits lactosylceramide to induce cell proliferation in UDP Gal:GlcCer: beta1 --> 4Galactosyltransferase (GalT-V) mutant Chinese hamster ovary cells.
Colonic Neoplasms
VEGF recruits lactosylceramide to induce endothelial cell adhesion molecule expression and angiogenesis in vitro and in vivo.
Glioblastoma
Over-expression of beta-1,4-galactosyltransferase V increases the growth of astrocytoma cell line.
Lymphoma
Selenium reduces enterohemorrhagic Escherichia coli O157:H7 verotoxin production and globotriaosylceramide receptor expression on host cells.
Melanoma
Human melanoma and Chinese hamster ovary cells galactosylate n-alkyl-beta-glucosides using UDP gal:GlcNAc beta 1,4 galactosyltransferase.
Melanoma
Positive regulation of tumor necrosis factor-alpha by ganglioside GM3 through Akt in mouse melanoma B16 cells.
Melanoma, Experimental
Expression machinery of GM4: the excess amounts of GM3/GM4S synthase (ST3GAL5) are necessary for GM4 synthesis in mammalian cells.
Neoplasms
Correlated gene expression between beta-1,4-galactosyltransferase V and N-acetylglucosaminyltransferase V in human cancer cell lines.
Neoplasms
Platelet derived growth factor recruits lactosylceramide to induce cell proliferation in UDP Gal:GlcCer: beta1 --> 4Galactosyltransferase (GalT-V) mutant Chinese hamster ovary cells.
Neoplasms
Sequential action of Ets-1 and Sp1 in the activation of the human beta-1,4-galactosyltransferase V gene involved in abnormal glycosylation characteristic of cancer cells.
Neoplasms
Transcriptional regulation of the human beta-1,4-galactosyltransferase V gene in cancer cells: essential role of transcription factor Sp1.
Neuroblastoma
Trichothecenes induce accumulation of glucosylceramide in neural cells by interfering with lactosylceramide synthase activity.
Pectus Carinatum
Skeletal dysplasia, global developmental delay, and multiple congenital anomalies in a 5-year-old boy-Report of the second family with B3GAT3 mutation and expansion of the phenotype.
Polycystic Kidney Diseases
The Yin and Yang of lactosylceramide metabolism: Implications in cell function.
Refractive Errors
Skeletal dysplasia, global developmental delay, and multiple congenital anomalies in a 5-year-old boy-Report of the second family with B3GAT3 mutation and expansion of the phenotype.
Skin Abnormalities
Skeletal dysplasia, global developmental delay, and multiple congenital anomalies in a 5-year-old boy-Report of the second family with B3GAT3 mutation and expansion of the phenotype.
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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
0.0613
recombinant enzyme, pH and temperature not specified in the publication
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
isoform beta4GalT5 works predominantly in mouse embryonic fibroblasts
brenda
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from normal and familial hypercholesterolemic homozygotes. Urinary proximal tubular cells from familial hypercholesterolemic homozygous patients contain glucosylceramide beta-1,4-galactosyltransferase activity 35% higher as compared to control cells
brenda
additional information
male mice show much higher activity of LacCer synthesis than female mice in the kidney. Expression levels of the B4galt5 gene correlate with the LacCer synthase activity in the kidney
brenda
additional information
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expression levels of B4galt6 gene is almost equivalent between male and female mice
brenda
additional information
expression levels of B4galt6 gene is almost equivalent between male and female mice
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
elevated glucosylceramide beta-1,4-galactosyltransferase activity may contribute to the storage of lactosylceramide urinary proximal tubular cells from familial hypercholesterolemic patients
physiological function
B4galt6 KO mice are born and grow up apparently normal. LacCer synthase activity and the composition of acidic glycosphingolipids in the brain are almost equivalent or minimally different between wild-type and KO mice. B4GalT6 does not act as a major beta4GalT on the modification of glycoproteins
physiological function
the amounts of Lac-Cer and ganglioside GM3 are significantly less in a stable clone E5 whose beta4GalT5 gene expression level is reduced to 35% than in a control clone C1 by transfection of its antisense cDNA. The average tumor size and average number of colonies formed with clone E5 are decreased to 44 and 49%, respectively, of those formed with clone C1. The numbers and sizes of colonies formed in the soft agarose gels, and the volumes of tumors formed in athymic mice with fibroblasts from wild type, heterozygous and homozygous beta4GalT5-knockout mouse embryos upon transformation with the polyoma virus oncogene correlate with the beta4GalT5 gene dosage
physiological function
generation of conditional knockout B4galt5 and B4galt6 double KO mice in the central nervous system. Lactosylceramide synthase activity and major brain gangliosides are completely absent in brain homogenates from the double KO mice, although Lactosylceramide synthase activity is about half its normal level in B4galt5 coditional KO mice and B4galt6 KO mice. The double KO mice are born normally but show growth retardation and motor deficits at 2 weeks and die by 4 weeks of age. Myelin-associated proteins are rarely found localized in axons in the cerebral cortex, and axonal and myelin formation are remarkably impaired in the spinal cords of the double KO mice. Neuronal cells, differentiated from isolated neurospheres, show impairments in neurite outgrowth and branch formation. The neurons are immature and perineuronal nets are poorly formed in double KO cerebral cortices
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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). B4GT5_DANRE
381
1
44335
Swiss-Prot
Secretory Pathway (Reliability: 3)
B4GT5_HUMAN
388
1
45119
Swiss-Prot
Secretory Pathway (Reliability: 4)
B4GT5_MOUSE
388
1
44814
Swiss-Prot
Secretory Pathway (Reliability: 4)
B4GT5_PIG
388
1
45046
Swiss-Prot
Secretory Pathway (Reliability: 4)
B4GT6_HUMAN
382
1
44914
Swiss-Prot
Secretory Pathway (Reliability: 4)
B4GT6_MOUSE
382
1
44759
Swiss-Prot
Secretory Pathway (Reliability: 3)
B4GT6_RAT
382
1
44778
Swiss-Prot
Secretory Pathway (Reliability: 3)
A0A061IJR6_CRIGR
329
0
38656
TrEMBL
Mitochondrion (Reliability: 5)
A0A061ID44_CRIGR
275
0
32270
TrEMBL
other Location (Reliability: 3)
A0A6J8DKG1_MYTCO
371
1
43146
TrEMBL
Mitochondrion (Reliability: 5)
A0A6J8DU83_MYTCO
336
0
39363
TrEMBL
other Location (Reliability: 2)
A0A6J8DVP5_MYTCO
248
0
28605
TrEMBL
other Location (Reliability: 3)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
contains about 15% N-linked carbohydrate. The polypeptide contains eight putative glycosylation sites
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Sf9 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
B4GALT5 expression is upregulated in PRRSV infected porcine alveolar macrophage
B4GALT5 gene/protein expression is specifically increased in human colorectal cancer
gene expression increases by 2-3fold upon malignant transformation of cells
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
the amounts of Lac-Cer synthesized by isoform beta4GalT5 correlate with the tumorigenic potentials of malignantly transformed cells
medicine
B4GALT5 expression is upregulated in porcine reproductive and respiratory syndrome virus (PRRSV) infected porcine alveolar macrophage. The PRRSV proliferation is slightly inhibited by overexpression of B4GALT5. B4GALT5 and PRRSV protein GP5 colocalize in Golgi membrane. mRNA transcription, including inflammatory cytokines IFN-alpha, IL-6, IL-18, IL-1beta, TNF-alpha and some cell surface glycosylated proteins involved in antigen presentation (MHC-I/II), cell adhesion and migration (chemokine MCP-1 and receptor CCR2; LFA-1, ICAM-1) are upregulated in B4GALT5 overexpressing PRRSV infected cells
medicine
B4GALT5 gene/protein expression is specifically increased in human colorectal cancer tumors, with a concomitant increase in its enzymatic activity, and product lactosylceramide, and increased dihydrosphingolipid metabolites. Inhibition of glycosphingolipid synthesis by the synthetic ceramide analog, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, concurrently inhibits colorectal cancer cell proliferation, as well as B4GALT5 mass and several glycosphingolipid levels
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Trinchera, M.; Fiorilli, A.; Ghidoni, R.
Localization in the Golgi apparatus of rat liver UDP-Gal:glucosylceramide beta1-4galactosyltransferase
Biochemistry
30
2719-2724
1991
Rattus norvegicus
brenda
Takizawa, M.; Nomura, T.; Wakisaka, E.; Yoshizuka, N.; Aoki, J.; Arai, H.; Inoue, K.; Hattori, M.; Matsuo, N.
cDNA cloning and expression of human lactosylceramide synthase
Biochim. Biophys. Acta
1438
301-304
1999
Homo sapiens (Q9UBX8)
brenda
Chatterjee, S.; Castiglione, E.
UDPgalactose:glucosylceramide beta1->4-galactosyltransferase activity in human proximal tubular cells from normal and familial hypercholesterolemic homozygotes
Biochim. Biophys. Acta
923
136-142
1987
Homo sapiens
brenda
Chatterjee, S.; Ghosh, N.; Khurana, S.
Purification of uridine diphosphate-galactose:glucosyl ceramide, beta1-4 galactosyltransferase from human kidney
J. Biol. Chem.
267
7148-7153
1992
Homo sapiens
brenda
Nomura, T.; Takizawa, M.; Aoki, J.; Arai, H.; Inoue, K.; Wakisaka, E.; Yoshizuka, N.; Imokawa, G., Dohmae, N.; Takio, K.; Hattori, M.; Matsuo, N.
Purification, cDNA cloning, and expression of UDP-Gal:glucosylceramide beta-1,4-galactosyltransferase from rat brain
J. Biol. Chem.
273
13570-13577
1998
Rattus norvegicus
brenda
Kumagai, T.; Sato, T.; Natsuka, S.; Kobayashi, Y.; Zhou, D.; Shinkai, T.; Hayakawa, S.; Furukawa, K.
Involvement of murine beta-1,4-galactosyltransferase V in lactosylceramide biosynthesis
Glycoconj. J.
27
685-695
2010
Mus musculus
brenda
Tokuda, N.; Numata, S.; Li, X.; Nomura, T.; Takizawa, M.; Kondo, Y.; Yamashita, Y.; Hashimoto, N.; Kiyono, T.; Urano, T.; Furukawa, K.; Furukawa, K.
beta4GalT6 is involved in the synthesis of lactosylceramide with less intensity than beta4GalT5
Glycobiology
23
1175-1183
2013
Mus musculus, Mus musculus (Q9JMK0)
brenda
Shirane, K.; Kuji, R.; Tareyanagi, C.; Sato, T.; Kobayashi, Y.; Furukawa, S.; Murata, T.; Kubota, S.; Ishikawa, Y.; Segawa, K.; Furukawa, K.
Gene expression levels of beta4-galactosyltransferase 5 correlate with the tumorigenic potentials of B16-F10 mouse melanoma cells
Glycobiology
24
532-541
2014
Mus musculus (Q9JMK0)
brenda
Chatterjee, S.B.; Hou, J.; Bandaru, V.V.R.; Pezhouh, M.K.; Syed Rifat Mannan, A.A.; Sharma, R.
Lactosylceramide synthase beta-1,4-GalT-V A novel target for the diagnosis and therapy of human colorectal cancer
Biochem. Biophys. Res. Commun.
508
380-386
2019
Homo sapiens (O43286)
brenda
Yoshihara, T.; Satake, H.; Nishie, T.; Okino, N.; Hatta, T.; Otani, H.; Naruse, C.; Suzuki, H.; Sugihara, K.; Kamimura, E.; Tokuda, N.; Furukawa, K.; Fururkawa, K.; Ito, M.; Asano, M.
Lactosylceramide synthases encoded by B4galt5 and 6 genes are pivotal for neuronal generation and myelin formation in mice
PLoS Genet.
14
e1007545
2018
Mus musculus (Q9JMK0), Mus musculus (Q9WVK5)
brenda
Zhang, L.; Ren, L.; Shi, P.; Lu, D.; Zhao, C.; Su, X.; Zhang, L.; Huang, J.
The immunological regulation roles of porcine beta-1,4 galactosyltransferase V (B4GALT5) in PRRSV infection
Front. Cell. Infect. Microbiol.
8
48
2018
Sus scrofa (A0A1S6M251)
brenda
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