Information on EC 2.4.1.80 - ceramide glucosyltransferase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
2.4.1.80
-
RECOMMENDED NAME
GeneOntology No.
ceramide glucosyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
UDP-glucose + an N-acylsphingosine = UDP + a D-glucosyl-N-acylsphingosine
show the reaction diagram
UDP-glucose and inhibitor D-PDMP binding region overlap and contain His193
-
UDP-glucose + an N-acylsphingosine = UDP + a D-glucosyl-N-acylsphingosine
show the reaction diagram
enzyme DNA sequence contains conserved D1,D2,D3,QXXRW motif found also in other progressive beta-glycosyltransferases, putative active site, Cys207 and His193 involved
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexosyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Metabolic pathways
-
-
sphingolipid biosynthesis (plants)
-
-
Sphingolipid metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
UDP-glucose:N-acylsphingosine D-glucosyltransferase
Sphingosine and dihydrosphingosine can also act as acceptors; CDP-glucose can act as donor.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ceramide glucosyltransferase
-
-
ceramide glucosyltransferase
O18037, Q21054
-
ceramide glucosyltransferase
-
-
ceramide glycosyltransferase
-
-
ceramide:UDP-glucose glucosyltransferase
-
-
-
-
ceramide:UDPGlc glucosyltransferase
-
-
-
-
cerebroside synthase
-
-
CGT
O18037, Q21054
-
cgt-1
-
gene name
cgt-1
O18037
the Caenorhabditis elegans genome encodes three ceramide glucosyltransferase (CGT) genes
cgt-2
-
gene name
cgt-2
-
the Caenorhabditis elegans genome encodes three ceramide glucosyltransferase (CGT) genes
cgt-3
-
gene name; isoforms with highest activity
cgt-3
Q21054
the Caenorhabditis elegans genome encodes three ceramide glucosyltransferase (CGT) genes
GCS
Rattus norvegicus Sprague-Dawley
-
-
-
GlcCer synthase
-
-
GlcCer synthase
-
-
GlcCer synthase
-
-
GlcCerS
-
-
GlcT
-
-
GlcT-1
-
-
glucosylceramide synthase
-
-
-
-
glucosylceramide synthase
-
-
glucosylceramide synthase
-
-
glucosylceramide synthase
-
-
glucosylceramide synthase
-
-
glucosylceramide synthase
-
-
glucosylceramide synthase
-
-
glucosylceramide synthase
-
-
glucosyltransferase, uridine diphosphoglucose-ceramide
-
-
-
-
UDP glucose-ceramide glucosyltransferase
-
-
-
-
UDP-Glc:ceramide glucosyltransferase
-
-
UDP-glucoase:ceramide glucosyltransferase
O88693
-
UDP-glucose ceramide glucosyltransferase
-
-
UDP-glucose ceramide glucosyltransferase
-
-
UDP-glucose ceramide glycosyltransferase
-
-
UDP-glucose:ceramide glucosyltransferase
-
-
-
-
UDP-glucose:ceramide glucosyltransferase
-
-
UDP-glucose:ceramide glucosyltransferase
-
-
Ugcg
-
-
Ugcg
O88693
-
uridine diphosphate (UDP)-glucose:N-acylsphingosine D-glucosyltransferase
-
-
uridine diphosphoglucose-ceramide glucosyltransferase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
37237-44-8
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
isoform A; mutants without CGT; isoform c; mutants without CGT
TREMBL
Manually annotated by BRENDA team
isoform B; mutants without CGT; isoform d; mutants without CGT; mutants without CGT
-
-
Manually annotated by BRENDA team
mutants without CGT
TREMBL
Manually annotated by BRENDA team
several isoforms
-
-
Manually annotated by BRENDA team
; MDCK cells
-
-
Manually annotated by BRENDA team
COS7 cells
-
-
Manually annotated by BRENDA team
zebrafish
-
-
Manually annotated by BRENDA team
13-14 days old embryo
-
-
Manually annotated by BRENDA team
gene GluT-1
-
-
Manually annotated by BRENDA team
hairless mice strain Cr1:SKH1-hr
-
-
Manually annotated by BRENDA team
Sprague-Dawley
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
In an analysis of microarray data of in a large cohort of 1681 breast tumors, there was a benefit for disease free survival for patients with tumors displaying low levels of GCS expression, especially in tumors with a positive estrogen receptor (ER) status.
malfunction
-
inhibiting UDP-glucose ceramide glycosyltransferase increases the susceptibility of p53-deficient cells, but not p53-expressing cells, to mitomycin C. Enzyme down-regulation contributes to the accumulation of ceramide in cells lacking p53
malfunction
-
reduced enzyme expression in the fat body causes a reduction of fat storage
malfunction
-
silencing glucosylceramide synthase expression disrupts Gb3 synthesis and selectively kills breast cancer stem cells through deactivation of c-Src/beta-catenin signaling
malfunction
-
when each gene function is disrupted, the brood size of the animal markedly decreases and abnormal oocytes and multinucleated embryos are formed. Knockdown of the germline expression of gene cgt-3 results in abnormal oocyte formation and abnormal embryonic cell division
metabolism
-
key enzyme for the synthesis of glycosphingolipids which plays a role in physiology and diseases for instance in drug-resistant cancers
physiological function
-
glucosylceramide synthase expression in the fat body regulates energy metabolism in Drosophila melanogaster
physiological function
-
the Ugcg gene is indispensable in the gremlin in oocyte formation and early embryonic division
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
TDP-glucose + N-acylsphingosine
TDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + 6-([(N-7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]caproyl)sphingosine
UDP + N-(6-((4-nitrobenz-2-oxa-1,3-diazol-7-yl)amino)caproyl)-O1-D-glucosyl-sphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + 6-([(N-7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]caproyl)sphingosine
UDP + N-(6-((4-nitrobenz-2-oxa-1,3-diazol-7-yl)amino)caproyl)-O1-D-glucosyl-sphingosine
show the reaction diagram
-
synthetic fluorescent substrate in liposomes for assay method development
-
-
?
UDP-glucose + C6-ceramide
UDP + glucosyl-C6-ceramide
show the reaction diagram
-
-
-
-
?
UDP-glucose + C6-ceramide
UDP + C6-glucosylceramide
show the reaction diagram
-
with fluorescent NBD C6-ceramide resulting in NBD C6-glucosylceramide direct quantification of ceramide glycosylation catalyzed by GCS in cells and in tissues are possible
-
-
?
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
-
-
-
?
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
-
-
-
?
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
-
-
-
?
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
-
-
-
ir
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
-
-
-
?
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
-
-
-
?
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
-
glucosylceramide is a precursor for synthesis of a multitude of higher sphingolipids
-
?
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
-
glucosylceramide is the core structure of major glycosphingolipids
-
?
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
ceramide and its metabolites are important mediators of apoptosis and cell survival
-
-
?
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
key enzyme in the synthesis of major glycosphingolipids in vertebrates
glucosylceramide is the core structure of major glycosphingolipids
-
?
UDP-glucose + ceramide
UDP + D-glucosyl-ceramide
show the reaction diagram
-
-
-
-
?
UDP-glucose + decasphingosine
UDP + D-glucosyl-decasphingosine
show the reaction diagram
-
-
-
?
UDP-glucose + dihydroceramide
UDP + D-glucosyl-dihydroceramide
show the reaction diagram
-
mono-, tri-, and tetrahexosylceramides, the parasite enzyme is only active on the saturated substrate
product analysis
-
?
UDP-glucose + dihydrosphingosine
UDP + D-glucosyl-dihydrosphingosine
show the reaction diagram
-
-
-
?
UDP-glucose + dihydrosphingosine
UDP + D-glucosyl-dihydrosphingosine
show the reaction diagram
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
-
dihydrosphingosine is no substrate
-
-
-
UDP-glucose + lauroyl amide
UDP + D-glucosyllauroyl amide
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-(epsilon-7-nitrobenz-2-oxa-1,3-diazol-4-yl-aminocaproyl)-D-erythro-sphingosine
?
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-6-[(7-nitrobenzo-2-oxa-1,3-diazol-4-yl)amino]hexanoyl-4-D-erythro-sphingosine
UDP + N-(6-((4-nitrobenz-2-oxa-1,3-diazol-7-yl)amino)caproyl)-O1-D-glucosyl-sphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-acylsphinganine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
stereospecific and dependent on nature and chain length of N-acylsphinganine substrate
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
acceptor substrate specificity, overview
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
acceptor substrate specificity, overview
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
acceptor substrate specificity, overview
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
specific for UDP-glucose
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
specific for ceramide substrate with trihydroxy sphingoside bases, ceramides with dihydroxy sphingoside bases are inactive, overview
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
Q16739
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
Q9R0E0
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
stereospecific and dependent on nature and chain length of N-acylsphingosine substrate, UDP-glucose is the preferred donor substrate
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
overview: short-chain ceramide substrates
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
overview: short-chain ceramide substrates
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
regulation of intracellular ceramide is closely related to drug resistance and DOX-induced apoptosis
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
enzyme is involved in renal growth, neuronal differentiation, the establishment of the water permeability barrier in keratinocytes, and multidrug resistance in cancer cell
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
ceramide plays an important role in signal transduction, regulation, and cell homeostasis, thus its glycosylation may play a role in regulation of the cellular level of the bioactive lipid
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
enzyme is required for normal permeability barrier homeostasis
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
catalyzes the first step during the sequential addition of carbohydrate moieties for ganglioside biosynthesis
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
catalyzes the first step during the sequential addition of carbohydrate moieties for ganglioside biosynthesis
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
initial key enzyme in glycosphingolipid biosynthesis
-
-
-
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
initial key enzyme in glycosphingolipid biosynthesis
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
initial key enzyme in glycosphingolipid biosynthesis
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
initial key enzyme in glycosphingolipid biosynthesis
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
initial key enzyme in glycosphingolipid biosynthesis
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
enzyme activity is regulated developmentally
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
first step in synthesis of gangliosides
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
Q16739
first step in synthesis of gangliosides
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
key step in biosynthesis of glycosphingolipids
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
key step in biosynthesis of glycosphingolipids
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
first step in the biosynthesis of glucosylceramide-based glycosphingolipids
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
Q58FH5
GCS is a key regulator of pathogenicity of Cryptococcus neoformans by ensuring cell cycle progression and growth of fungal cells in environments characterized by neutral/alkaline pH and physiological concentrations of CO2. Since these environments are characteristically found in the lung alveolar spaces, GCS regulates survival of Cryptococcus neoformans upon inhalation through the respiratory tract, with important implications for the dissemination of fungal cells to the brain and the development of meningo-encephalitis
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
the enzyme catalyzes a necessary step in the conversion of ceramide to glycosphingolipids
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
the enzyme catalyzes the initial step of glycosphingolipid biosynthesis
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
the transient formation of glucosylceramide is vital for a regular arrangement of lipids and proteins in lamellar bodies and for the maintenance of the epidermal barrier
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
Q58FH5
Cryptococcus neoformans Gcs1 expressed in Saccharomyces cerevisiae is unable to recognize 7-nitro-2-1,3-benzoxadiazol-4-yl-ceramide analogs as substrates
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
Ugcg-deficient mice die between postnatal day 11 and postnatal day 24. Glycosphingolipids are required for brain maturation after birth
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
catalyzes the first step during the sequential addition of carbohydrate moieties for ganglioside biosynthesis
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
i.e. ceramide
i.e. glucosylceramide
?
UDP-glucose + N-octanoyl sphingosine
UDP + D-glucosyl-N-octanoyl sphingosine
show the reaction diagram
-
best substrate
-
?
UDP-glucose + N-octanoyl sphingosine
UDP + D-glucosyl-N-octanoyl sphingosine
show the reaction diagram
-
best substrate
-
?
UDP-glucose + N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]-6-aminocaproyl-D-erythro-sphingosine
UDP + D-glucosyl-N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]-6-aminocaproyl-D-erythro-sphingosine
show the reaction diagram
-
synthetic fluorescent ceramide substrate analogue for fluorescence enzyme assay
-
-
?
UDP-glucose + N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]-6-aminocaproyl-D-erythro-sphingosine
UDP + D-glucosyl-N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]-6-aminocaproyl-D-erythro-sphingosine
show the reaction diagram
Q9R0E0
synthetic fluorescent ceramide substrate analogue for fluorescence enzyme assay
-
-
?
UDP-glucose + N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]-6-aminocaproyl-D-erythro-sphingosine
UDP + D-glucosyl-N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]-6-aminocaproyl-D-erythro-sphingosine
show the reaction diagram
-
synthetic fluorescent ceramide substrate analogue for fluorescence enzyme assay
-
-
?
UDP-glucose + N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]-6-aminocaproyl-D-erythro-sphingosine
UDP + D-glucosyl-N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]-6-aminocaproyl-D-erythro-sphingosine
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
synthetic fluorescent ceramide substrate analogue for fluorescence enzyme assay
-
-
?
UDP-glucose + sphingosine
UDP + D-glucosyl-sphingosine
show the reaction diagram
-
-
-
?
CDP-glucose + N-acylsphingosine
CDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
i.e. ceramide
i.e. glucosylceramide
?
additional information
?
-
-
octanoyl dihydrosphingosine, decanoyl sphingosine, and stearoyl sphingosine are poor substrates
-
-
-
additional information
?
-
-
enzyme decreases apoptosis and induces multidrug resistance, functional interaction with RTN-1C modulates enzyme activity and regulates chemotherapeutic-induced apoptosis in neuroepithelioma cells
-
-
-
additional information
?
-
-
lipid profile of the parasite at different developmental stages, overview
-
-
-
additional information
?
-
-
the enzyme has dual function as negative regulator of cell death mediated by proapoptotic factors and in catalyzing the formation of glucosylceramide, the core structure of major glycosphingolipids, ceramide generation might be a signal pathway
-
-
-
additional information
?
-
-
NBD ceramide is used as substrate
-
-
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
-
-
-
?
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
-
glucosylceramide is a precursor for synthesis of a multitude of higher sphingolipids
-
?
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
ceramide and its metabolites are important mediators of apoptosis and cell survival
-
-
?
UDP-glucose + ceramide
UDP + glucosylceramide
show the reaction diagram
-
key enzyme in the synthesis of major glycosphingolipids in vertebrates
glucosylceramide is the core structure of major glycosphingolipids
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
-
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
regulation of intracellular ceramide is closely related to drug resistance and DOX-induced apoptosis
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
enzyme is involved in renal growth, neuronal differentiation, the establishment of the water permeability barrier in keratinocytes, and multidrug resistance in cancer cell
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
ceramide plays an important role in signal transduction, regulation, and cell homeostasis, thus its glycosylation may play a role in regulation of the cellular level of the bioactive lipid
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
enzyme is required for normal permeability barrier homeostasis
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
catalyzes the first step during the sequential addition of carbohydrate moieties for ganglioside biosynthesis
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
catalyzes the first step during the sequential addition of carbohydrate moieties for ganglioside biosynthesis
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
initial key enzyme in glycosphingolipid biosynthesis
-
-
-
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
initial key enzyme in glycosphingolipid biosynthesis
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
initial key enzyme in glycosphingolipid biosynthesis
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
initial key enzyme in glycosphingolipid biosynthesis
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
initial key enzyme in glycosphingolipid biosynthesis
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
enzyme activity is regulated developmentally
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
first step in synthesis of gangliosides
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
Q16739
first step in synthesis of gangliosides
i.e. glucosylceramide
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
key step in biosynthesis of glycosphingolipids
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
key step in biosynthesis of glycosphingolipids
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
first step in the biosynthesis of glucosylceramide-based glycosphingolipids
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
Q58FH5
GCS is a key regulator of pathogenicity of Cryptococcus neoformans by ensuring cell cycle progression and growth of fungal cells in environments characterized by neutral/alkaline pH and physiological concentrations of CO2. Since these environments are characteristically found in the lung alveolar spaces, GCS regulates survival of Cryptococcus neoformans upon inhalation through the respiratory tract, with important implications for the dissemination of fungal cells to the brain and the development of meningo-encephalitis
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
the enzyme catalyzes a necessary step in the conversion of ceramide to glycosphingolipids
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
the enzyme catalyzes the initial step of glycosphingolipid biosynthesis
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
-
the transient formation of glucosylceramide is vital for a regular arrangement of lipids and proteins in lamellar bodies and for the maintenance of the epidermal barrier
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
catalyzes the first step during the sequential addition of carbohydrate moieties for ganglioside biosynthesis
-
-
?
UDP-glucose + N-acylsphingosine
UDP + D-glucosyl-N-acylsphingosine
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
-
i.e. glucosylceramide
?
additional information
?
-
-
enzyme decreases apoptosis and induces multidrug resistance, functional interaction with RTN-1C modulates enzyme activity and regulates chemotherapeutic-induced apoptosis in neuroepithelioma cells
-
-
-
additional information
?
-
-
lipid profile of the parasite at different developmental stages, overview
-
-
-
additional information
?
-
-
the enzyme has dual function as negative regulator of cell death mediated by proapoptotic factors and in catalyzing the formation of glucosylceramide, the core structure of major glycosphingolipids, ceramide generation might be a signal pathway
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ba2+
-
activates
Ca2+
-
stimulates
Ca2+
-
stimulates
Ca2+
-
stimulates; stimulates
Mg2+
-
not required
Mg2+
-
stimulates
Mg2+
-
stimulates
Mg2+
-
stimulates
Mg2+
-
stimulates; stimulates
Mg2+
-
stimulates
Mg2+
-
-
Mn2+
-
not required
Mn2+
-
stimulates
Mn2+
-
stimulates
Mn2+
-
stimulates
Mn2+
-
stimulates; stimulates
Mn2+
-
stimulates
additional information
-
no stimulation by metal ions
additional information
-
no stimulation by metal ions
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1R)-1-C-octyl-N-octyl-1,5-dideoxy-1,5-imino-D-glucitol
-
-
(1R)-N-butyl-1-C-butyl-1,5-dideoxy-1,5-imino-D-glucitol
-
-
(1S)-1-C-[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin
-
-
(1S)-N-butyl-1-C-[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin
-
-
(2S,3R)-2-(hydroxymethyl)pyrrolidin-3-ol
-
0.05 mM, about 15% inhibition
(2S,3R,4S)-2-(hydroxymethyl)-4-octylpyrrolidin-3-ol
-
0.01 mM, about 70% inhibition
(2S,3R,4S)-4-butyl-2-(hydroxymethyl)pyrrolidin-3-ol
-
0.05 mM, about 30% inhibition
(D-threo)-1-(3',4'-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol
-
the inhibitor is abolutely specific for the recombinant human enzyme and does not affect recombinant non-human enzymes from Gossypium arboreum, Caenorhabditis elegans, Aspergillus nidulans, Candida albicans, Pichia pastoris, Ustilago maydis, or Agrobacterium tumefaciens
(D-threo)-1-phenyl-2-decanoylamino-3-morpholino-1-propanol
-
specific inhibitor
1-phenyl-2-decanoylamino-3-morpholino-1-propanol
-
-
-
2-decanoylamido-3-morpholinopropiophenone
-
45% inhibition at 0.3 mM
arsenic trioxide
-
treatment of a human acute promyelocytic leukemia cell line (NB4) and adult T-cell leukemia/lymphoma (ATL) derived cells with arsenic trioxide induces accumulation of cytoxic levels of ceramide which results from de novo ceramide synthesis and inhibition of glucosylceramide synthase activity
CDP-glucose
-
slight inhibition
CDP-glucose
-
slight inhibition
CHAPS
-
i.e. 3-[(3-cholamidopropyl)dimethylammonio]-1propanesulfonate
Cu2+
-
-
Cu2+
-
-
D,L-threo-1-phenyl-2-(decanoylamino)-3-morpholino-1-propanol-HCl
-
accumulation of ceramide in the cells, higher amount in Z65 mutant than in strain K1
D,L-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol
-
enzyme inhibition in vitro and in vivo, in the latter case the compound also inhibits growth of the parasite
D-threo-1-phenyl-2-(decanoylamino)-3-morpholino-1-propanol-HCl
-
i.e. PDMP
D-threo-1-phenyl-2-(decanoylamino)-3-morpholino-1-propanol-HCl
-
i.e. PDMP
D-threo-1-phenyl-2-(decanoylamino)-3-morpholino-1-propanol-HCl
-
-
D-threo-1-phenyl-2-(decanoylamino)-3-morpholino-1-propanol-HCl
-
His193 mutants are not inhibited; i.e. PDMP
D-threo-1-phenyl-2-(decanoylamino)-3-morpholino-1-propanol-HCl
-
in vivo depletion of enzyme and accumulation of ceramide; not DL-diastereomer
D-threo-1-phenyl-2-(decanoylamino)-3-morpholino-1-propanol-HCl
-
;
D-threo-1-phenyl-2-(decanoylamino)-3-morpholino-1-propanol-HCl
-
accumulation of ceramide in the cells, higher amount in Z65 mutant than in strain K1
D-threo-2-palmitoylamino-3-pyrrolidino-1-propanol
-
-
Detergents
-
e.g. 0.5% Triton X-100 or 0.5% sodium deoxycholate; inhibition of enzyme due to permeabilization of microsomal membrane
diethyl dicarbonate
-
i.e. DEPC; reversible by hydroxylamine, UDP-glucose protects, inhibitor acts on histidine residues, including His193, within or near UDP-glucose binding site
DL-threo-1-phenyl-2-hexadecanoyl-amino-3-pyrrolidino-1-propanol
-
i.e. most active PDMP-type congener, specific and reversible, in vivo and in vitro
Doxorubicin
-
i.e. DOX; increases enzyme activity in drug-sensitive cell line HL-60, but not in drug-resistant HL-60/ADR cell line; regulation of intracellular ceramide is closely related to drug resistance and DOX-induced apoptosis
EDTA
-
-
EDTA
-
no inhibition
Fe2+
-
-
Fe2+
-
-
Fe3+
-
-
Fe3+
-
-
N-(5'-adamantan-1'-yl-methoxy)-pentyl-1-deoxynojirimycin
-
highly specific small molecule inhibitor of glucosylceramide synthase. When administered to mice and rats, it significantly reduces glycosphingolipid but not ceramide concentrations in various tissues. Treatment of ob/ob mice with the inhibitor normalizes their elevated tissue glucosylceramide levels, markedly lowers circulating glucose levels, improves oral glucose tolerance, reduced A1C, and improves insulin sensitivity in muscle and liver
N-(5'-adamantane-1'-yl-methoxy)-pentyl-1-deoxynojirimycin
-
pharmacological inhibition of glucosylceramide synthase enhances insulin sensitivity
N-butyl 1-deoxynojirimycin
-
-
N-butyl-1-deoxynojirimycin
-
-
N-butyl-2,4-di-O-butyl-1,5-dideoxy-1,5-imino-D-glucitol
-
1 mM, 29% inhibition
N-butyldeoxynojirimycin
-
-
N-butyldeoxynojirimycin
-
-
N-butyldeoxynojirimycin
-
nonspecific inhibitor
N-ethylmaleimide
-
attacks Cys207
N-octyl-2-O-octyl-1,5-dideoxy-1,5-imino-D-glucitol
-
-
N-octyl-4-O-octyl-1,5-dideoxy-1,5-imino-D-glucitol
-
-
N-[5-(adamantan-1-yl-ethoxy)-pentyl]-L-ido-1-deoxynojirimycin
-
-
N-[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin
-
-
N-[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin
-
-
N-[5-(adamantan-1-yl-methoxy)-pentyl]-L-ido-1-deoxynojirimycin
-
-
octyl glucoside
-
high concentration
octyl thioglucoside
-
-
Phospholipase A
-
treatment of microsomes results in loss of enzyme actvity
-
Phospholipase C
-
treatment of microsomes results in loss of enzyme actvity
-
PP55B
-
i.e. isopropylidene derivative of 5'-O-[[(2-decanoylamino-3-phenylpropylloxycarbonyl)amino]sulfonyl]uridine, 21% inhibition at 0.2 mM
threo-1-phenyl-2-decanoyl-amino-3-morpholino-1-propanol
-
inhibition at 0.005 mM
-
Tris
-
at high concentration
Tris
-
58% loss of activity at 0.2 M
Triton X-100
-
high concentration
Triton X-100
-
-
Trypsin
-
-
-
Zn2+
-
-
Zn2+
-
-
Zwittergent 3-12
-
complete inhibition
Genz-112638
-
inhibitor is tested in a murine model of Gaucher disease (D409V/null): mice that receive drug prior to significant accumulation of substrate show reduced levels of glucosylceramide and number of Gaucher cells in the spleen, lung and liver when compared to control. Treatment of older mice that already display significant amounts of tissue glucosylceramide results in arrest of further accumulation of the substrate and appearance of additional Gaucher cells in affected organs; substrate inhibition therapy with Genz-112638 represents an approach to enzyme therapy to treat the visceral pathology in Gaucher diseases
additional information
-
no inhibition by EDTA
-
additional information
-
-
-
additional information
-
induction of enzyme by inhibitors in presence of higher ceramide levels
-
additional information
-
induction of enzyme by inhibitors in presence of higher ceramide levels; no inhibition by conduritol B epoxide
-
additional information
-
-
-
additional information
-
-
-
additional information
-
no inhibition by DTT
-
additional information
-
enzyme inhibition by antisense expression
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
c-Fos
-
activity of glucosylceramide synthase is around 5fold higher in presence of high c-Fos levels, induced by nerve growth factor NGF, addition of c-Fos mRNA ASO, which specifically blocks c-Fos expression abolished the induction of glucosylceramide synthase by NGF
-
CHAPS
-
i.e. 3-[(3-cholamidopropyl)dimethylamonio]-1propanesulfonate
CHAPS
-
i.e. 3-[(3-cholamidopropyl)dimethylamonio]-1propanesulfonate
cycloserine
-
induction
Detergent
-
-
-
Detergent
-
absolute requirement for; optimal activity obtained with a mixture of Cutsum and Triton X-100 (2:1)
-
Detergent
-
activity is reduced by most of the detergents tested, only CHAPS and CHAPSO at concentration of 1% w/v stimulate
-
Detergent
-
CHAPS stimulates
-
dioleoyl phosphatidylcholine
-
or other exogenous phospholipid, required for activity
HSP70
-
dog heat shock protein 70 increases production of glucosylceramide to 207%
-
HSP70
-
dog heat shock protein 70 increases production of glucosylceramide to 149%
-
L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol
-
L-PDMP treatment induces a 2.4 increase in glucosylceramide
NAD+
-
stimulation, best at 2 mM
NADH
-
omission in assay containing Golgi vesicles leads to loss of about 90% activity
NADH
-
stimulation
NADP+
-
stimulation
NADPH
-
stimulation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.04055
C6-ceramide
-
in tumor of NCI/ADR-RES
0.054
ceramide
-
-
0.08
ceramide
-
-
0.292
ceramide
-
-
0.013
N-(6-((4-nitrobenz-2-oxa-1,3-diazol-7-yl)amino)caproyl)-O1-D-glucosyl-sphingosine
-
in absence of c-Fos
0.02
N-(6-((4-nitrobenz-2-oxa-1,3-diazol-7-yl)amino)caproyl)-O1-D-glucosyl-sphingosine
-
in presence of c-Fos
0.03877
NBD C6-ceramide
-
substrate is fluorescent
0.0069
UDP-glucose
-
in absence of c-Fos
0.0079
UDP-glucose
-
in presence of c-Fos
0.0087
UDP-glucose
-
-
0.022
UDP-glucose
-
-
0.12
UDP-glucose
-
-
0.2
UDP-glucose
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.174
(1R)-1-C-octyl-N-octyl-1,5-dideoxy-1,5-imino-Dglucitol
-
-
0.609
(1R)-N-butyl-1-C-butyl-1,5-dideoxy-1,5-imino-D-glucitol
-
-
0.009
(1S)-1-C-[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin
-
-
0.025
(1S)-N-butyl-1-C-[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin
-
-
0.000024
Genz-112638
-
-
0.02
N,N'-(5,5'-[2-(adamantan-1-yl)propane-1,3-diyl]bis-(oxy)bis(pentane-5,1-diyl))-bis(1-deoxynojirimycin)
-
in vivo inhibition of a cell culture
0.04
N,N'-(5,5'-[2-(adamantan-1-yl)propane-1,3-diyl]bis-(oxy)bis(pentane-5,1-diyl))-bis(1-deoxynojirimycin)
-
in vitro inhibition of purified enzyme
0.01
N,N'-(5,5'-[2-(adamantan-1-yl)propane-1,3-diyl]bis-(oxy)bis(pentane-5,1-diyl))-bis(L-ido-1-deoxynojirimycin)
-
in vitro inhibition of purified enzyme
0.02
N,N'-(5,5'-[2-(adamantan-1-yl)propane-1,3-diyl]bis-(oxy)bis(pentane-5,1-diyl))-bis(L-ido-1-deoxynojirimycin)
-
in vivo inhibition of a cell culture
0.02
N,N'-(5,5'-[adamantan-1,3-diylbis(methylene)]bis(oxy)-bis(pentane-5,1-diyl))-bis(1-deoxynojirimycin)
-
in vivo inhibition of a cell culture
0.04
N,N'-(5,5'-[adamantan-1,3-diylbis(methylene)]bis(oxy)-bis(pentane-5,1-diyl))-bis(1-deoxynojirimycin)
-
in vitro inhibition of purified enzyme
0.005
N,N'-(5,5'-[adamantan-1,3-diylbis(methylene)]bis(oxy)-bis(pentane-5,1-diyl))-bis(L-ido-1-deoxynojirimycin)
-
in vivo inhibition of a cell culture
0.01
N,N'-(5,5'-[adamantan-1,3-diylbis(methylene)]bis(oxy)-bis(pentane-5,1-diyl))-bis(L-ido-1-deoxynojirimycin)
-
in vitro inhibition of purified enzyme
0.164
N-octyl-2-O-octyl-1,5-dideoxy-1,5-imino-D-glucitol
-
-
0.134
N-octyl-4-O-octyl-1,5-dideoxy-1,5-imino-D-glucitol
-
-
0.001
N-[5-(adamantan-1-yl-ethoxy)-pentyl]-1-deoxynojirimycin
-
in vivo inhibition of a cell culture
0.005
N-[5-(adamantan-1-yl-ethoxy)-pentyl]-1-deoxynojirimycin
-
in vitro inhibition of purified enzyme
0.001
N-[5-(adamantan-1-yl-ethoxy)-pentyl]-L-ido-1-deoxynojirimycin
-
in vivo inhibition of a cell culture
0.005
N-[5-(adamantan-1-yl-ethoxy)-pentyl]-L-ido-1-deoxynojirimycin
-
in vitro inhibition of purified enzyme
0.0002
N-[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin
-
-
0.0002
N-[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin
-
in vivo inhibition of a cell culture
0.0005
N-[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin
-
in vitro inhibition of purified enzyme
0.0001
N-[5-(adamantan-1-yl-methoxy)-pentyl]-L-ido-1-deoxynojirimycin
-
in vivo inhibition of a cell culture
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00000034
-
CHO cell line mutant Z65
0.00000139
-
CHO cell line K-1
0.0000065
-
-
0.0000082
-
whole epidermis
0.00017
-
recombinant enzyme in cell extract of cell line KB-3-1
0.0002
-
microsomal fraction, 30C
0.00021
-
recombinant enzyme in cell extract of cell line KB-A1
0.00024
-
recombinant enzyme in cell extract of cell line KB-V.1
0.00025
-
recombinant enzyme in cell extract of cell line KB-A.05
0.00036
-
recombinant enzyme in cell extract of cell line KB-V1
0.0007
-
Golgi fraction
0.0436
-
purified enzyme
additional information
-
actvity in brain homogenates
additional information
-
-
additional information
-
assay method development
additional information
-
assay method development
additional information
-
-
additional information
-
-
additional information
-
fluorescence assay method; fluorescence assay method
additional information
-
-
additional information
-
assay method development
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.4 - 6.5
-
MES or Tris-maleate buffer
6.5
-
assay at
6.5
-
-
6.5
-
assay at
7.4
-
assay at; assay at
7.4
-
assay at
7.4
-
assay at
7.5
-
assay at
7.8
-
liver
7.8
-
assay at
8
-
assay at
8.2
-
brain
additional information
-
sharp fall of activity below and above pH 6.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 8.5
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 32
-
assay at
30
-
assay at
30
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at; assay at
37
-
assay at
37
-
assay at
37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
15 - 40
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
of leukaemic patients before chemotherapy
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
GCS expression is significantly decreased in cortex of Alzheimer disease patients
Manually annotated by BRENDA team
-
strain K1, and GM3-mutant strain Z65
Manually annotated by BRENDA team
-
ovary cells expressing the LT antigen
Manually annotated by BRENDA team
-
80% of the activity in outer epidermis, 20% in lower epidermis
Manually annotated by BRENDA team
-
cerebellar granule cells are treated with GCS inhibitor D-threo-2-palmitoylamino-3-pyrrolidino-1-propanol which induces an increase in log-chain ceramides, loss of viability and dramatic changes in neuron/neurite morphology
Manually annotated by BRENDA team
-
highest activity
Manually annotated by BRENDA team
-
it is shown that overexpression of the GCS gene is associated with multidrug resistance of leukemia cells
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
low level
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
peripheral blood cell of leukaemic patients before chemotherapy
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
U2OS-AS cell, construction of the pHA-E6S and pHA-E6AS plasmids, which respectively contain either the sense or the antisense versions of epitope-tagged E6 (HA-E6) under the control of the CMV promoter, and establishment of the U2OSE64b and U2OSE6AS cell lines by stable transfection with these plasmids has been described previously, U2OS-E6b4 cell, construction of the pHA-E6S and pHA-E6AS plasmids, which respectively contain either the sense or the antisense versions of epitope-tagged E6 (HA-E6) under the control of the CMV promoter, and establishment of the U2OSE64b and U2OSE6AS cell lines by stable transfection with these plasmids has been described previously
Manually annotated by BRENDA team
additional information
-
ubiquitous distribution
Manually annotated by BRENDA team
additional information
-
enzyme is expressed in all developmental stages
Manually annotated by BRENDA team
additional information
-
intraerythrocytic stages of the parasite
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
integral membrane protein
Manually annotated by BRENDA team
-
orientation to the cytosolic side
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
orientation to the cytosolic side
-
Manually annotated by BRENDA team
-
enzyme contains a membrane-spanning region
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
associated with membranes, structural integrity of the microsomal membranes is essential for activity
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
associated with membranes, structural integrity of the microsomal membranes is essential for activity
-
-
Manually annotated by BRENDA team
additional information
-
enzyme is not associated with synaptosomes and myelin
-
Manually annotated by BRENDA team
additional information
-
type III membrane protein
-
Manually annotated by BRENDA team
additional information
-
N-terminal and TM regions of the enzyme are required for localization in the Golgi apparatus
-
Manually annotated by BRENDA team
additional information
Rattus norvegicus Sprague-Dawley
-
enzyme is not associated with synaptosomes and myelin
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
66000
-
sedimentation in a glycerol gradient
489416
additional information
-
amino acid sequence
489413
additional information
-
amino acid sequence alignment
489416
additional information
-
amino acid sequence alignment; type III membrane protein structure with N-terminal signal-anchor sequence and a long cytoplasmic tail
489416
additional information
-
amino acid sequence alignment
489416
additional information
-
amino acid sequence alignment; type III membrane protein structure with N-terminal signal-anchor sequence and a long cytoplasmic tail
489416
additional information
-
C- and N-terminal amino acid sequences; enzyme forms dimeric or oligomeric complexes with another protein in the Golgi membrane vivo, topology
489418
additional information
-
partial amino acid sequence alignment
489419
additional information
-
; enzyme forms dimeric or oligomeric complexes with another protein in the Golgi membrane vivo, topology
489421
additional information
-
-
489421
additional information
-
; enzyme forms dimeric or oligomeric complexes with another protein in the Golgi membrane vivo, topology
489421
additional information
-
amino acid sequence of conserved D1,D2,D3,QXXRW motif
489423
additional information
-
amino acid sequence; signal anchor domain, glycosylation site
489424
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 38000, SDS-PAGE
?
-
x * 45000, SDS-PAGE
?
-
x * 60000-66000, SDS-PAGE
?
-
x * 448530, amino acid sequence determination
?
-
x * 38000, native and recombinant enzyme, SDS-PAGE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
brain enzyme, half-life: 50 min at various temperatures
-
NAD+ stabilizes
-
no loss of activity during freezing and subsequent thawing
-
glycerol stabilizes
-
labile enzyme
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70C, 0.2 M MOPS, 0.25 M sucrose, pH 6.5, stable for more than 3 months
-
-70C, enzyme in intact kidneys is stable for at least 90 days
-
4C, enzyme in intact kidneys, 53% loss of activity after overnight storage
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partial from Golgi membranes
-
partial from Golgi membranes; solubilization method
-
solubilization method
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning and transient expression in GM-95 cell line, mutant cell line containing no enzyme activity, derived from melanoma mutant cell line B16, DNA sequence determination and analysis
-
expressed in GM95 cells deficient in glycosphingolipids
-
functional expression of 1 isozyme in Saccharomyces cerevisiae strain 334
-
cloning of wild-type and construction of knock-out mutant, functional expression in Saccharomyces cerevisiae strain 334, expression of wild-type leads to accumulation of beta-D-glucopyranosyl ceramides, absent in wild-type Saccharomyces cerevisiae, knock-out mutation is not lethal
-
cloning from CHO cell line K1, overexpression in GM3-mutant CHO cell line Z65, DNA and amino acid sequence determination
-
expression in Saccharomyces cerevisiae
Q58FH5
gene GlcT-1, DNA sequence determination and analysis, functional expression in enzyme-deficient GM-95 cells, expression as V5/His-tagged protein in GM95 cells
-
functional expression in membranes of a Pichia pastoris enzyme-deficient double-null mutant strain, also lacking sterol glucosyltransferase activity
-
cloning and transient expression in GM-95 cell line, mutant cell line containing no enzyme activity, derived from melanoma mutant cell line B16, DNA sequence determination and analysis
-
cloning and transient expression in GM-95 cell line, mutant cell line containing no enzyme activity, derived from melanoma mutant cell line B16, DNA sequence determination and analysis; functional expression in Escherichia coli BL21(DE3)
-
expressed in different drug-resistant human cancer cell lines
-
expressed in PC12 cells
-
expression in an enzyme-deficient strain of Pichia pastoris
-
expression of enzyme gene in antisense orientation, two-hybrid system: coexpression with the reticulon RTN family, interaction especially with RTN-1C
-
functional expression in Escherichia coli BL21(DE3)
-
gene GluT-1 cloned from a human melanoma genetic library, transient overexpression in HL-60 and HL-60/ADR cells, induced resistance to DOX in HL-60 cells
-
overexpression in cancer cell lines selected for resistance to natural product chemotherapy, i.e. cell lines KB-3-1, KB-V.01, KB-V.1, KB-V1, KB-A.05, MCF-7, and MCF-7-AdrR, cell lines show different recombinant enzyme activity, which is higherin cells resistant to natural product anticancer agents, e.g. vinblastine and adriamycin, overview
-
functional expression in Saccharomyces cerevisiae strain 334
-
expressed as recombinant protein
-
cloning from rat brain genetic library and expression in Escherichia coli BL21(DE3)
-
expression of wild-type and mutants in Escherichia coli BL21(DE3)
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
HSP70 influence on gene expression
-
after 24 h under a 42C heat stress, GluT mRNA significantly increased to 714%
-
cell culture under 42C heat stress for 24 h, increase of gene expression to 714%
-
HSP70 influence on gene expression
-
cell culture under 42C heat stress for 17 h, increase of gene expression to 142%
-
after 17 h under a 42C heat stress, GluT mRNA increased to 142%
-
the mixed-backbone oligonucleotide MBO-asGCS decreases mRNA levels in human tumor cell lines by 65%
-
in the absence of p53, mitomycin C treatment elicits a down-regulation of the enzyme
-
glucosylceramide synthase expression is enhanced in breast cancer stem cells but not in normal mammary epithelial stem cells
-
the mixed-backbone oligonucleotide MBO-asGCS considerable decreases mRNA levels in murine tumor cell lines
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C143A
-
site-directed mutagenesis, increased activity, reduced expression level compared to wild-type
C207A
-
site-directed mutagenesis, reduced activity, reduced inhibitory effect of N-ethylmaleimide, reduced expression level compared to wild-type
C213A
-
site-directed mutagenesis, reduced activity, reduced expression level compared to wild-type
C232A
-
site-directed mutagenesis, reduced expresssion level compared to wild-type
C290A
-
site-directed mutagenesis, reduced expression level compared to wild-type
C296A
-
site-directed mutagenesis, reduced activity, reduced expression level compared to wild-type
C321A
-
site-directed mutagenesis, reduced activity
C321A/C323A
-
site-directed mutagenesis, reduced activity
C343A
-
site-directed mutagenesis, enhanced activity, slightly reduced expression level compared to wild-type
C384A
-
site-directed mutagenesis, enhanced activity
C86A
-
site-directed mutagenesis, reduced activity, reduced expression level compared to wild-type
C98A
-
site-directed mutagenesis, reduced activity, reduced expression level compared to wild-type
H169A
-
26.4% activity compared to wild-type, reduced inhibition by diethyldicarbonate and increased protection by UDP-glucose
H193A
-
33.0% activity compared to wild-type, reduced inhibition by diethyldicarbonate and reduced protection by UDP-glucose
H193D
-
no activity
H193N
-
23.0% activity compared to wild-type, reduced inhibition by diethyldicarbonate and reduced protection by UDP-glucose
H193R
-
no activity
H26A
-
5.2% activity compared to wild-type
H26D
-
10.5% activity compared to wild-type
H26N
-
44.5% activity compared to wild-type
H26R
-
118.5% activity compared to wild-type, slightly enhanced inhibition by diethyldicarbonate and slightly reduced protection by UDP-glucose
H308A
-
35.2% activity compared to wild-type, slightly reduced inhibition by diethyldicarbonate and slightly reduced protection by UDP-glucose
H308A/H309A
-
10.8% activity compared to wild-type
H309A
-
69.1% activity compared to wild-type
H322A
-
3.8% activity compared to wild-type
H322D
-
2.6% activity compared to wild-type
H322N
-
49.8% activity compared to wild-type, slightly enhanced inhibition by diethyldicarbonate and slightly reduced protection by UDP-glucose
H322R
-
no activity
H36A
-
103.2% activity compared to wild-type, slightly enhanced inhibition by diethyldicarbonate and slightly reduced protection by UDP-glucose
additional information
-
animals lacking CGT do not synthesize glycosphingolipids, arrest growth at the first larval stage, and display defects in a subset of cells in their digestive tract, restoring CGT function in these digestive tract cells but not in a variety of other tissues is sufficient to rescue the phenotypes associated with loss of CGT function
additional information
-
loss of enzyme function by RNA interference leads to increased apoptotic cell death, conversely targeted expression of the enzyme can rescue cell death, overview
DELTAFgGCS1
-
a null mutation of the FgGCS1 gene becomes resistant to antifungal defensins MsDef1, but not to MtDef4 from Medicago. It shows a significant change in the conidial morphology and displays dramatic polar growth defect, and its mycelia are resistant to cell wall degrading enzymes.GCS1 is not required for pathogenicity of Fusarium graminearum
additional information
-
antisense expression inhibits enzyme activity
additional information
O88693
Ugcg flox/flox, mice that lack oligodendroglial expression of Ugcg, no influence on glycosphingolipid content in brain and myelin extracts
H90A
-
119.3% activity compared to wild-type
additional information
-
deletion mutants, lacking the first 10 or the last 8 amino acid residues, show only 4% of the wild-type activity
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
reconstitution of solubilized enzyme in detergent-free lipid vesicles
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
molecular biology
-
glucosylceramide is essential for MsDef1-mediated growth inhibition of Fusarium graminearum, but not for its pathogenicity
medicine
-
-
medicine
-
potential therapeutic target for inherited sphingolipidoses such as Gaucher, Fabry, and Tay-Sachs disease
medicine
-
GCS expression is significantly down-regulated in Alzheimer brain
medicine
-
results show that high level of GCS in leukemia cells is associated with multidrug resistance of these cells
medicine
-
it is shown that pharmacological lowering of glycosphingolipids, without significant reduction of ceramide, dramatically reverses insulin resistance in in vitro and in vivo models and may present a novel approach to the therapy of type 2 diabetes
medicine
-
substrate inhibition therapy with Genz-112638 represents a viable alternate approach to enzyme therapy to treat the visceral pathology in Gaucher disease
pharmacology
-
enzyme might be an attractive target for malarial chemotherapy
medicine
-
enzyme inhibition is a possible target for chemotherapeutic agents for a number of diseases, including cancer