Information on EC 2.4.99.8 - alpha-N-acetylneuraminate alpha-2,8-sialyltransferase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY
2.4.99.8
-
RECOMMENDED NAME
GeneOntology No.
alpha-N-acetylneuraminate alpha-2,8-sialyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
CMP-N-acetylneuraminate + alpha-N-acetylneuraminyl-(2->3)-beta-D-galactosyl-R = CMP + alpha-N-acetylneuraminyl-(2->8)-alpha-N-acetylneuraminyl-(2->3)-beta-D-galactosyl-R
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
glycosyl group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Glycosphingolipid biosynthesis - ganglio series
-
Glycosphingolipid biosynthesis - globo series
-
Glycosphingolipid biosynthesis - lacto and neolacto series
-
Metabolic pathways
-
SYSTEMATIC NAME
IUBMB Comments
CMP-N-acetylneuraminate:alpha-N-acetylneuraminyl-(2->3)-beta-D-galactoside alpha-(2->8)-N-acetylneuraminyltransferase
Gangliosides act as acceptors.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
alpha-2,8-sialyltransferase
-
-
-
-
alpha-2,8-sialyltransferase 8A
-
-
-
-
alpha2,8-sialyltransferase
-, Q50J31, Q50J32, Q50J33, Q50J34, Q50J35, Q6KC13
-
alpha2,8-sialyltransferase
P97325
-
alpha2,8-sialyltransferase
Q64687, Q8K4T1
-
alpha2,8-sialyltransferase
Q6DNG6
-
alpha2,8-sialyltransferase
Q6ZXA0
-
alpha2,8S-T
-
-
CMP-NAcNeu:GM3 ganglioside sialyltransferase
-
-
-
-
CMP-NeuAc:GD3(alpha 2-8) sialyltransferase
-
-
-
-
CMP-NeuAc:GM3 alpha 2,8-sialyltransferase
-
-
CMP-NeuAc:LM1(alpha 2-8) sialyltransferase
-
-
-
-
CMP-sialic acid:GM3 sialyltransferase
-
-
-
-
CST-II
Campylobacter jejuni OH4384
-
-
-
ganglioside GD3 synthase
-
-
-
-
ganglioside GD3 synthetase
-
-
-
-
ganglioside GD3-synthase
-
-
ganglioside GT3 synthase
-
-
-
-
GD3 synthase
-
-
-
-
GD3 synthase
-
-
GD3 synthase
-
-
GD3 synthase
Q6DNG6
-
GD3 synthase
Q6ZXA0
-
GD3 synthase long isoform
Q6ZXA0
-
GD3 synthase short isoform
Q6ZXA0
-
hST8Sia III
-
-
membrane-associated polysialyltransferase
-
-
polysialyltransferase
Q92187
-
polysialyltransferase
O35696
-
polysialyltransferase
Q64692
-
polysialyltransferase
-
-
Pst
Q92187
-
Pst
Q64692
-
SAT-2
-
-
-
-
Sia-alpha2,3-Gal-beta1,4-GlcNAc-R:alpha2,8-sialyltransferase
-
-
sialyltransferase
-
-
sialyltransferase II
-
-
-
-
sialyltransferase, cytidine monophosphoacetylneuraminate-ganglioside GM3
-
-
-
-
sialyltransferase-X
O35696
-
ST-II
-
-
-
-
ST8Sia I
Q6ZXA0
-
ST8Sia-1
-
-
ST8Sia-I
Q64687
isoform
ST8Sia-VI
Q8K4T1
isoform
ST8SiaI
Q6KC13
-
ST8SiaII
Q50J31
-
ST8SiaII
O35696
also known as STX
ST8SiaII
O35696
isoform
ST8SiaII
O35696
isoform, STX
St8SiaIII
B0CN48
-
St8SiaIII
Q50J32
-
St8SiaIII
P97325
-
ST8SiaIV
Q50J33
-
ST8SiaIV
Q92187
-
ST8SiaIV
Q64692
also known as PST
ST8SiaIV
Q64692
isoform
ST8SiaIV
Q64692
isoform, PST
ST8SiaV
Q50J34
-
ST8SiaVI
Q50J35
-
ST8SiaVIIA
-
-
Stx
O35696
-
CAS REGISTRY NUMBER
COMMENTARY
67339-00-8
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
bifunctional sialyltransferase with both alpha2,3-sialyltransferase and alpha2,8-sialyltransferase activities
-
-
Manually annotated by BRENDA team
Campylobacter jejuni OH4384
-
-
-
Manually annotated by BRENDA team
7 genes of alpha2,8-sialyltransferase are found in Danio rerio
-
-
Manually annotated by BRENDA team
7 genes of alpha2,8-sialyltransferase are found in Danio rerio
UniProt
Manually annotated by BRENDA team
7 genes of alpha2,8-sialyltransferase are found in Danio rerio
Uniprot
Manually annotated by BRENDA team
enzyme is weakly expressed during nervous system development
UniProt
Manually annotated by BRENDA team
9 days old embryonic brains
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
expression in CHO cell, coexpression with calnexin suppresses enzyme-induced apoptosis
-
-
Manually annotated by BRENDA team
recombinant enzyme
-
-
Manually annotated by BRENDA team
recombinant protein
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
isoform ST8SiaII
SwissProt
Manually annotated by BRENDA team
isoform ST8SiaII
SwissProt
Manually annotated by BRENDA team
isoform ST8SiaIV
SwissProt
Manually annotated by BRENDA team
serogroup B
-
-
Manually annotated by BRENDA team
cichlid fish
-
-
Manually annotated by BRENDA team
12-14 days old
-
-
Manually annotated by BRENDA team
female Wistar
-
-
Manually annotated by BRENDA team
Sprague-Dawley
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
-
-
Manually annotated by BRENDA team
sequence leads to two ST8Sia I mRNAs, the canonical form constituted of 5 exons and 4 introns, and the short mRNA lacking the exon 2; isoform ST8Sia I, present as short an long mRNA species. During development, the mRNA is detectable starting at 8 h post fertilization, the onset of gastrulation, with its short sequence. After 24 h the messenger is mainly represented by the long one.There is a marked increase of the mRNA after 15 days of development
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
polysialyltransferase ST8SiaIV knockout mice display a decreased motivation in social interaction. This deficit can be partly explained by olfactory deficits and was associated with a clear decrease in acid polysialic acid-neuronal cell adhesion molecule expression in brain. Sialyltransferase-X knockout mice display both a decreased social motivation and an increased aggressive behavior and show mild increase of polysialic acid-neuronal cell adhesion molecule expression in the lateral septum and the orbitofrontal cortex
metabolism
-
sphingolipid metabolism
metabolism
Q64687, Q8K4T1
isoform ST8Sia-I is involved in the synthesis of ganglioside GD3; isoform ST8Sia-VI isinvolved in the synthesis of disialic acid structures on O-glycans
physiological function
Q64692
sensory experience-dependent ST8SiaII gene expression regulates polysialic acid levels in postnatal visual cortex, thus acting as molecular link between visual activity and polysialic acid expression
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
CMP-alpha-N-acetylneuraminate + alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
-
-
-
-
CMP-alpha-N-acetylneuraminate + alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
branch-point enzyme in ganglioside biosynthetic sequence
-
-
?
CMP-alpha-N-acetylneuraminate + NeuAc-alpha2,8-NeuAc-alpha2,3-Gal-beta1,4-Glc-beta-FCHASE
GMP + ?
show the reaction diagram
-
-
-
-
?
CMP-N-acetylneuraminate + (11-azidoundecyl 5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosid)onic acid
CMP + 11-azidoundecyl O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid + 11-azidoundecyl O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid + 11-azidoundecyl O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid + 11-azidoundecyl O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid + 11-azidoundecyl O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid
show the reaction diagram
Campylobacter jejuni, Campylobacter jejuni OH4384
-
-
12%, 7.7%, 5.3%, 4.5%, and 2.2% yield, respectively
-
?
CMP-N-acetylneuraminate + (methyl S-5-acetamido-3,5-dideoxy-2-thio-D-glycero-alpha-D-galacto-non-2-ulopyranosyl)onic acid
CMP + methyl O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-5-acetamido-3,5-dideoxy-2-thio-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid + methyl O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-5-acetamido-3,5-dideoxy-2-thio-D-glycero-alpha-D-galactonon-2-ulopyranosylonic acid
show the reaction diagram
Campylobacter jejuni, Campylobacter jejuni OH4384
-
-
17% and 10.1% yield, respectively
-
?
CMP-N-acetylneuraminate + 4-chlorophenyl 6-S-(5-acetamido-3,5-dideoxy-2-thio-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->6)-1,6-dithio-beta-D-galactopyranoside
CMP + 4-chlorophenyl O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->8)-(5-acetamido-3,5-dideoxy-2-thio-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->6)-S-1,6-dithio-beta-D-galactopyranoside
show the reaction diagram
Campylobacter jejuni, Campylobacter jejuni OH4384
-
-
-
-
?
CMP-N-acetylneuraminate + alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-N-acetyl-beta-D-glucosaminyl-1,3-beta-D-galactosyl-1,4-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-N-acetyl-beta-D-glucosaminyl-1,3-beta-D-galactosyl-1,4-D-glucosylceramide
show the reaction diagram
-
i.e. sialosylneolactotetraosylceramide or ganglioside LM1
i.e. disialosylneolactotetraosylceramide or ganglioside LD1c
?
CMP-N-acetylneuraminate + beta-sialic acid
CMP + alpha-N-acetylneuraminyl-(2->8)-beta-N-acetylneuraminate
show the reaction diagram
Campylobacter jejuni, Campylobacter jejuni OH4384
-
-
21.5% yield
-
?
CMP-N-acetylneuraminate + bovine submaxillary mucin
CMP + ?
show the reaction diagram
Q64687, Q8K4T1
substrate for isoform ST8Sia-VI, 100% activity
-
-
?
CMP-N-acetylneuraminate + disialoganglioside GD1a
CMP + trisialoganglioside GT1a
show the reaction diagram
-
-
-
?
CMP-N-acetylneuraminate + ganglioside GM3
CMP + ?
show the reaction diagram
-
-
-
-
?
CMP-N-acetylneuraminate + ganglioside GM3
CMP + ?
show the reaction diagram
Q64687, Q8K4T1
substrate for isoform ST8Sia-I, 100% activity
-
-
?
CMP-N-acetylneuraminate + methyl S-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galactonon-2-ulopyranosylonic acid)-(2->6)-(6-thio-beta-D-galactopyranosyl)-(1->4)-O-beta-D-glucopyranoside
CMP + methyl O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galactonon-2-ulopyranosylonic acid)-(2->8)-(5-acetamido-3,5-dideoxy-2-thio-D-glycero-alpha-D-galacto-non-2-ulopyranosylonic acid)-(2->6)-(6-thio-beta-D-galactopyranosyl)-(1->4)-beta-D-glucopyranoside
show the reaction diagram
-
-
19% yield
-
?
CMP-N-acetylneuraminate + N-acyl-lyso-GM3
CMP + N-acyl-lyso-GD3
show the reaction diagram
-
N-acetyl derivative is a better substrate than GM3, detergent-like effect
-
?
CMP-N-acetylneuraminate + N-alpha-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
-
-
-
?
CMP-N-acetylneuraminate + N-alpha-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
-
i.e. disialosyllactosylceramide or ganglioside GD3
?
CMP-N-acetylneuraminate + N-alpha-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
-
i.e. disialosyllactosylceramide or ganglioside GD3
?
CMP-N-acetylneuraminate + N-alpha-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
-
i.e. disialosyllactosylceramide or ganglioside GD3
?
CMP-N-acetylneuraminate + N-alpha-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
-
i.e. disialosyllactosylceramide or ganglioside GD3
?
CMP-N-acetylneuraminate + N-alpha-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
-
i.e. disialosyllactosylceramide or ganglioside GD3
?
CMP-N-acetylneuraminate + N-alpha-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
-
i.e. disialosyllactosylceramide or ganglioside GD3
?
CMP-N-acetylneuraminate + N-alpha-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
-
i.e. disialosyllactosylceramide or ganglioside GD3
?
CMP-N-acetylneuraminate + N-alpha-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
-
i.e. disialosyllactosylceramide or ganglioside GD3
?
CMP-N-acetylneuraminate + N-alpha-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
-
i.e. disialosyllactosylceramide or ganglioside GD3
?
CMP-N-acetylneuraminate + N-alpha-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
i.e. sialosyllactosylceramide or ganglioside GM3, specificity is determined by the substrate's negative charge and the acyl-residue in amide bond to the amino group of neuraminic acid, poor substrates are GM3 methyl ester, GM3 amide or GM3 methyl amide, no substrates are neuraminyllactosylceramide or N-biotinylneuraminyllactosylceramide
i.e. disialosyllactosylceramide or ganglioside GD3
?
CMP-N-acetylneuraminate + N-butyrylneuraminyl-alpha-2,3-galactosyl-beta-1,4-glucosyl-beta-1,1-ceramide
CMP + ?
show the reaction diagram
-
sialylated at about 60% the rate of GM3
-
-
?
CMP-N-acetylneuraminate + N-glycolylneuraminyl-alpha-2,3-galactosyl-beta-1,4-glucosyl-beta-1,1-ceramide
CMP + ?
show the reaction diagram
-
-
-
-
?
CMP-N-acetylneuraminate + neural cell adhesion molecule
CMP + ?
show the reaction diagram
Q92187
-
-
-
?
CMP-N-acetylneuraminate + neuropilin-2
CMP + ?
show the reaction diagram
Q92187
-
-
-
?
CMP-N-acetylneuraminate + trisialoganglioside GT1b
CMP + ganglioside GQ1b
show the reaction diagram
-
-
-
?
CMP-Neu5Ac + GT3-FCHASE
CMP + long polySia chains + ?
show the reaction diagram
-
the trisialylganglioside analogue GT3-FCHASE as artificial acceptor substrate
-
-
?
additional information
?
-
-
mouse enzyme is specific toward N-linked oligosaccharides of glycoproteins
-
-
-
additional information
?
-
-
overexpression of recombinant UDP-GlcNAc 2-epimerase/ManNAc 6-kinase in human embryonic kidney (HEK AD293) cells leads to an increase in mRNA levels for ST3Gal5 (GM3 synthase) and ST8Sia1 (GD3 synthase) as well as the biosynthetic products of these sialyltransferases, the GM3 and GD3 gangliosides. Down-regulation of UDP-GlcNAc 2-epimerase/ManNAc 6-kinase by RNA interference methods has the opposite, but consistent, effect of lowering ST3Gal5 and ST8Sia1 mRNAs and reducing GM3 and GD3 levels
-
-
-
additional information
?
-
-
the expression of hST8Sia III gene via the PI-3K signaling pathway is enhanced during KCl-induced differentiation of U-87 cells by increasing expression of beta-tubulin III
-
-
-
additional information
?
-
-
NF-kappaB plays an essential role in the transcriptional activity of GD3 synthase gene in Fas-induced Jurkat T cells. The translocation of NF-kB-binding protein to nucleus by Fas activation is also crucial for the increased expression of the GD3 synthase gene in Fas-activated Jurkat T cells
-
-
-
additional information
?
-
-
the minimum number of sialic acid residues on the acceptor molecule for activity in vitro is two, with a large increase in activity if the acceptor carries three sialic residues. The polysialyltransferase from Neisseria meningitidis generates longer reaction products than the enzyme from Escherichia coli on synthetic FCHASE acceptors. Products are a heterogeneous mixture, including products with more than 50 Neu5Ac residues
-
-
-
additional information
?
-
-
enzyme is able to produce large polymers when it is part of the native capsule biosynthesis complex associated with the inner bacterial membrane, synthesizes long polysialic acid chains in a non-processive manner in vitro. PolyST activity towards short oligosialic acid acceptors (DP2 to DP5) is measured at constant CMP-Neu5Ac and enzyme concentrations
-
-
-
additional information
?
-
-
(4-chlorophenyl 5-acetamido-3,5-dideoxy-2-thio-D-glycero-alpha-D-galacto-non-2-ulopyranosid)onic acid is no substrate
-
-
-
additional information
?
-
Q64687, Q8K4T1
isoform ST8Sia-I shows no activity with bovine submaxillary mucin
-
-
-
additional information
?
-
Q64687, Q8K4T1
isoform ST8Sia-VI shows no activity towards ganglioside GM3
-
-
-
additional information
?
-
Campylobacter jejuni OH4384
-
(4-chlorophenyl 5-acetamido-3,5-dideoxy-2-thio-D-glycero-alpha-D-galacto-non-2-ulopyranosid)onic acid is no substrate
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
CMP-alpha-N-acetylneuraminate + alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
CMP + alpha-N-acetylneuraminyl-2,8-alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-glucosylceramide
show the reaction diagram
-
branch-point enzyme in ganglioside biosynthetic sequence
-
-
?
additional information
?
-
-
overexpression of recombinant UDP-GlcNAc 2-epimerase/ManNAc 6-kinase in human embryonic kidney (HEK AD293) cells leads to an increase in mRNA levels for ST3Gal5 (GM3 synthase) and ST8Sia1 (GD3 synthase) as well as the biosynthetic products of these sialyltransferases, the GM3 and GD3 gangliosides. Down-regulation of UDP-GlcNAc 2-epimerase/ManNAc 6-kinase by RNA interference methods has the opposite, but consistent, effect of lowering ST3Gal5 and ST8Sia1 mRNAs and reducing GM3 and GD3 levels
-
-
-
additional information
?
-
-
the expression of hST8Sia III gene via the PI-3K signaling pathway is enhanced during KCl-induced differentiation of U-87 cells by increasing expression of beta-tubulin III
-
-
-
additional information
?
-
-
enzyme is able to produce large polymers when it is part of the native capsule biosynthesis complex associated with the inner bacterial membrane
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-
slight activation
Mg2+
-
stimulation
Mg2+
-
up to 4fold stimulation in presence of 20 mM MgCl2. Strong preference for Mg2+ over other divalent cations
Mn2+
-
required
additional information
-
no metal ion requirement
additional information
-
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
AMP
-
less effective than CMP or GMP
CDP
-
only partially relieved by excess Mg2+
EDTA
-
Mg2+ protects
Ganglioside D1a
-
-
Ganglioside LM1
-
at higher concentrations, substrate inhibition
Ganglioside Q1b
-
strong
Ganglioside T1b
-
-
GMP
-
as strong as CMP
Lysophospholipids
-
-
-
N-ethylmaleimide
-
-
TMP
-
less effective than AMP
additional information
-
no inhibition by ganglioside GM2
-
additional information
-
IAA, 2-mercaptoethanol
-
additional information
-
no inhibition by Mg2+, CMP-N-acetylneuraminate
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
Myrj 59
-
activation, most potent activator, can be replaced by the following detergents, descending efficiency: sodium deoxycholate, Triton CF-54, Tween 20, Tween 80/Triton CF-54 ratio 1:*2, Triton X-100 or Tween 80
Nonidet P-40
-
activation
Triton CF-54
-
-
Triton CF-54
-
activation, further enhanced by supplementation with diacyl phospholipids
Triton CF-54
-
can be replaced by Triton X-100, Tween 80 or Tween 20 with 25%, 11% or 9% efficiency, respectively
Triton X-100
-
activation
Zwittergent 3-10
-
-
-
Zwittergent 3-14
-
-
Histone
-
slight activation
additional information
-
the presence of detergents is essential for activity, no activation by phosphatidylglycerol
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1.4
-
CMP-alpha-N-acetylneuraminate
-
pH 7.5, 37°C
3.2
-
CMP-alpha-N-acetylneuraminate
-
pH 7.5, 37°C
0.07
-
CMP-N-acetylneuraminate
-
-
0.081
-
CMP-N-acetylneuraminate
-
mutant R272A, pH 6.5, 37°C
0.088
-
CMP-N-acetylneuraminate
-
wild-type, pH 6.5, 37°C
0.11
-
CMP-N-acetylneuraminate
-
mutant S190A, pH 6.5, 37°C
0.22
-
CMP-N-acetylneuraminate
-
mutant N188D, pH 6.5, 37°C
0.8
-
CMP-N-acetylneuraminate
-
-
0.42
-
CMP-Neu5Ac
-
calculated and determined at constant donor concentration of 1 mM CMPNeu5Ac
0.078
-
ganglioside GM3
-
-
0.083
-
ganglioside GM3
-
wild-type, pH 6.5, 37°C
0.087
-
ganglioside GM3
-
mutant N188D, pH 6.5, 37°C
0.1
-
ganglioside GM3
-
-
0.184
-
ganglioside GM3
-
mutant S190A, pH 6.5, 37°C
0.2
-
ganglioside GM3
-
-
0.979
-
ganglioside GM3
-
mutant R272A, pH 6.5, 37°C
1
-
ganglioside GT1a
-
-
-
0.063
-
Ganglioside LM1
-
soluble enzyme preparation
0.12
-
NeuAc-alpha2,8-NeuAc-alpha2,3-Gal-beta1,4-Glc-beta-FCHASE
-
pH 7.5, 37°C
0.145
-
NeuAc-alpha2,8-NeuAc-alpha2,3-Gal-beta1,4-Glc-beta-FCHASE
-
pH 7.5, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00028
0.00055
-
-
0.00105
-
-
-
0.0189
-
-
-
additional information
-
-
the specific activity of both fusion proteins is increased 2fold compared with enzymes with short tags
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
7.2
-
trisialoganglioside formation
6.5
-
-
GM3 or GT1b as substrate
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
in primary neurons and astrocytes lacking GD3 synthase, amyloid beta-induced cell death and amyloid beta aggregation are inhibited
Manually annotated by BRENDA team
-
chronic ethanol consumption down-regulates CMP-NeuAc:GM3 alpha 2,8-sialyltransferase gene in the rat brain
Manually annotated by BRENDA team
-, Q50J31, Q50J32, Q50J33, Q50J34, Q50J35, Q6KC13
expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
tissue samples of primary invasive breast cancer cases
Manually annotated by BRENDA team
Q64687, Q8K4T1
;
Manually annotated by BRENDA team
-
the GD3 synthase gene may be involved in early tooth development, particularly in the proliferation of dental epithelium
Manually annotated by BRENDA team
-
human vascular endothelial cell line, overexpression of enzyme results in accelerated apoptosis accompanied by reduced phosphorylation of AKT and cyclic-AMP responsive element binding protein
Manually annotated by BRENDA team
-, Q50J31, Q50J32, Q50J33, Q50J34, Q50J35, Q6KC13
expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR
Manually annotated by BRENDA team
Q6DNG6, Q6ZXA0, -
normal quantity of ST8Sia I_short mRNA; traces of long form of ST8Sia mRNA together with a normal quantity of the short one; traces of of ST8Sia I_long mRNA
Manually annotated by BRENDA team
Q6DNG6, Q6ZXA0, -
normal quantity of ST8Sia I_long
Manually annotated by BRENDA team
-
GD3 synthase is involved in apoB secretion in retinoic acid-treated Chang liver cells via transcriptional induction of microsomal triglyceride transfer protein
Manually annotated by BRENDA team
-, Q50J31, Q50J32, Q50J33, Q50J34, Q50J35, Q6KC13
expression detected by RT-PCR; expression detected by RT-PCR
Manually annotated by BRENDA team
Q6DNG6, Q6ZXA0, -
high level of long form of ST8Sia mRNA; high level of ST8Sia I_long
Manually annotated by BRENDA team
Q6DNG6, Q6ZXA0, -
traces of long form of ST8Sia mRNA together with a normal quantity of the short one; traces of of ST8Sia I_long mRNA
Manually annotated by BRENDA team
Q6DNG6, Q6ZXA0, -
low expression of ST8Sia I_short mRNA; very low expression of short form of ST8Sia I mRNA
Manually annotated by BRENDA team
-
in primary neurons and astrocytes lacking GD3 synthase, amyloid beta-induced cell death and amyloid beta aggregation are inhibited
Manually annotated by BRENDA team
-
isoform ST8SiaII is the major polysialyltransferase in immature neurons of the paleocortex layer II and the hippocampal subgranular zone; isoform ST8SiaIV is solely responsible for PSA expression in mature interneurons and in most regions of cortical neuropil
Manually annotated by BRENDA team
-, Q50J31, Q50J32, Q50J33, Q50J34, Q50J35, Q6KC13
expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR
Manually annotated by BRENDA team
-
nuclear factor NF-kappaB plays an essential role in the transcriptional activity of human GD3 synthase gene
Manually annotated by BRENDA team
Q6DNG6, Q6ZXA0, -
marked presence of of ST8Sia I_short mRNA; marked presence of short form of ST8Sia I mRNA
Manually annotated by BRENDA team
B0CN48, -
enzyme is weakly expressed during nervous system development, and shows a highly dynamic expression pattern in somites and somite-derived structures
Manually annotated by BRENDA team
Q6DNG6, Q6ZXA0, -
low expression of ST8Sia I_short mRNA; very low expression of short form of ST8Sia I mRNA
Manually annotated by BRENDA team
-
the enzyme is highly expressed during the early stage of tooth germ development (embryonic day 14.5), especially in dental epithelia, not in dental mesenchymal tissue
Manually annotated by BRENDA team
-
up-regulation of hST8Sia III via phosphoinositide 3 kinase/AKT pathway results in the neuronal differentiation of U-87 cells by inducing expression of beta-tubulin III
Manually annotated by BRENDA team
Q6DNG6, Q6ZXA0, -
high level of long form of ST8Sia mRNA; high level of ST8Sia I_long
Manually annotated by BRENDA team
additional information
-
in wound-healing scratching assay, transfected 3T3 cells show enhanced mobility over transfected PC-12 cells; transfected cells show no enhancement in either cell proliferation or phosphorylation of MAP kinases when treated with platelet-derived growth factor. In wound-healing scratching assay, transfected 3T3-cells show enhanced mobility over transfected PC-12 cells
Manually annotated by BRENDA team
additional information
-
no expression in liver or skin
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
subcompartment termed mitochondria-associated membrane
Manually annotated by BRENDA team
-
retention of functional enzyme upon coexpression with calnexin
Manually annotated by BRENDA team
-
coexpression with calnexin prevents localization to Golgi apparatus
Manually annotated by BRENDA team
-
membrane association is not essential for enzyme functionality. Analyses performed with crude membrane fractions as enzyme source
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
additional information
-
50% of the wild-type polyST is soluble and enzymatically active, whereby the detected activity is 3fold higher in the soluble than in the insoluble fraction
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
45000
-
-
SDS-polyacrylamide-gel electrophoresis in the presence of beta-mercaptoethanol
55000
-
-
SDS-gel electrophoresis
95000
-
-
SDS-polyacrylamide-gel electrophoresis in the absence of beta-mercaptoethanol
100000
-
-
recombinant MBP-NmB-polyST, affinity chromatography and gel filtration, SDS-PAGE, Western blot analysis
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
Q6DNG6, Q6ZXA0, -
x * 47200, SDS-PAGE
?
Q92187
x * 50000, SDS-PAGE
additional information
-
subsequent structure-function analyses of NmB-polyST based on refined sequence alignments allowed the identification of two functional motifs in bacterial sialyltransferases. Both (D/E-D/E-G and HP motif) are highly conserved among different sialyltransferase families with otherwise little or no sequence identity. Removal of the C-terminal extension present in NmB but not in the homologous Escherichia coli enzymes, completely abolished enzymatic activity, proving it as an essential functional domain. Using site-directed mutagenesis and refined protein alignment strategies, identify two functionally important motifs, which are highly conserved in a number of bacterial (poly)sialyltransferases of otherwise unrelated sequences. T7-polyST, NusA-polyST, MBP-polyST, and Strep II-polyST: NmB-polyST fusion proteins with large fusion partners (MBP, NusA) are used
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
glycoprotein
-
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
secondary structure alignments between Campylobacter jejunii sialyltransferase CstII and human GD3-synthase. In the human enzyme, the side chain on residue N188 has a strong hydrogen bond with the carboxyl group on the sialic acid group of the donor substrate. Residue P189 has no interaction with the donor. The distance between S190 and the donor substrate is 4.4 A, this residue might weakly interact with the donor. R272 is 8.8 A away from the donor, suggesting that this residue has no function on donor substrate binding
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
56
-
-
20% loss of activity after 120 s
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
affinity and size exclusion chromatography
-
homogenized, centrifuged, resuspended in 25mM-cacodylate buffer pH 6.5 containing 0.15% Triton X-100, 75mM NaCl and 10 mM MnCl2
-
solubilized with Triton X-100, CDP-Sepharose affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-
expression in Escherichia coli
-
expression in CHO-K1 cells
-
cloning and sequence analysis of the 5'-flanking region of human GD3 synthase gene
-
expression in CHO-K1 cells. Secretion of mouse interleukin-2 signal sequence and transmembrane domain truncated human GD3-synthase cDNA amino-acid residues 49-356
-
expression in K-562 cell
-
expression of cDNA from melanoma cell line WM266-4 in Namalwa KJM-1 cells
-
expression in neuroblastoma cell line NG108-15
-
expression in newborn brain in mouse
-
expressed in Escherichia coli BL21(DE3)
-
expression in Escherichia coli
-
expression in CHOP cells
-
expression in neuroblastoma cell line F-11
-
cloning and nucleotide sequences of ST8Sia I_long cDNA; cloning and nucleotide sequences of ST8Sia I_short; expression in COS-7 cell
Q6DNG6, Q6ZXA0, -
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
no significant differences between the groups with high and low ST8SIA expression for age, tumor size, lymph node status, and Her 2 neu overexpression of patients
-
higher expression in estrogen receptor negative breast tumors, gene expression of ganglioside GD3 synthase is associated with prognosis in breast cancer
-
both isoforms ST8SiaII mRNA level decreases around the time of eye opening in mouse visual cortex; isoform ST8SiaIV mRNA level decreases around the time of eye opening in mouse visual cortex
Q64692
isoforms ST8SiaIV mRNA level is positively regulated by PKC-mediated signaling; isoform ST8SiaII mRNA level is positively regulated by protein kinase C-mediated signaling
Q64692
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
N188D
-
mutation in a conserved residue identified by structure alignments between Campylobacter jejunii sialyltransferase CstII and human GD3-synthase, 6fold decrease in ratio Km to Vmax
R272A
-
mutation in a conserved residue identified by structure alignments between Campylobacter jejunii sialyltransferase CstII and human GD3-synthase, 4fold decrease in ratio Km to Vmax
S190A
-
mutation in a conserved residue identified by structure alignments between Campylobacter jejunii sialyltransferase CstII and human GD3-synthase, 4fold decrease in ratio Km to Vmax
A281V
Q64687, Q8K4T1
the mutant of isoform ST8Sia-I shows 103.7% activity with ganglioside GM3
A328V
Q64687, Q8K4T1
the mutant of isoform ST8Sia-VI shows 77.2% activity with bovine submaxillary mucin
C286A
Q64687, Q8K4T1
the mutant of isoform ST8Sia-I shows no activity with ganglioside GM3
C335A
Q64687, Q8K4T1
the mutant of isoform ST8Sia-VI shows no activity with bovine submaxillary mucin
E288N
Q64687, Q8K4T1
the mutant of isoform ST8Sia-I shows 66.5% activity with ganglioside GM3
E333G
Q64687, Q8K4T1
the mutant of isoform ST8Sia-VI shows no activity with bovine submaxillary mucin
F277M
Q64687, Q8K4T1
the mutant of isoform ST8Sia-I shows 81.1% activity with ganglioside GM3
G284E
Q64687, Q8K4T1
the mutant of isoform ST8Sia-I shows no activity with ganglioside GM3
I291L
Q64687, Q8K4T1
the mutant of isoform ST8Sia-I shows 95.3% activity with ganglioside GM3
I327L
Q64687, Q8K4T1
the mutant of isoform ST8Sia-VI shows 90% activity with bovine submaxillary mucin
K339S
Q64687, Q8K4T1
the mutant of isoform ST8Sia-VI shows 34.6% activity with bovine submaxillary mucin
L278I
Q64687, Q8K4T1
the mutant of isoform ST8Sia-I shows 11.9% activity with ganglioside GM3
L283V
Q64687, Q8K4T1
the mutant of isoform ST8Sia-I shows 45.4% activity with ganglioside GM3
L340I
Q64687, Q8K4T1
the mutant of isoform ST8Sia-VI shows 18.6% activity with bovine submaxillary mucin
N337E
Q64687, Q8K4T1
the mutant of isoform ST8Sia-VI shows no activity with bovine submaxillary mucin
S273A
Q64687, Q8K4T1
the mutant of isoform ST8Sia-I shows no activity with ganglioside GM3
S290K
Q64687, Q8K4T1
the mutant of isoform ST8Sia-I shows 72.4% activity with ganglioside GM3
S322A
Q64687, Q8K4T1
the mutant of isoform ST8Sia-VI shows no activity with bovine submaxillary mucin
V279A
Q64687, Q8K4T1
the mutant of isoform ST8Sia-I shows 85.6% activity with ganglioside GM3
V330A
Q64687, Q8K4T1
the mutant of isoform ST8Sia-VI shows 92% activity with bovine submaxillary mucin
V332L
Q64687, Q8K4T1
the mutant of isoform ST8Sia-VI shows 69.8% activity with bovine submaxillary mucin
W295A
Q64687, Q8K4T1
the mutant of isoform ST8Sia-I shows 3.3% activity with ganglioside GM3; the mutant of isoform ST8Sia-I shows 3.3% activity with ganglioside GM3
W344A
Q64687, Q8K4T1
the mutant of isoform ST8Sia-VI shows no activity with bovine submaxillary mucin
E153A
-
inactive, single-point mutation of NmB-polyST by QuickChange site-directed mutagenesis
G154A
-
inactive, single-point mutation of NmB-polyST by QuickChange site-directed mutagenesis
H278A
-
nearly inactive, single-point mutation of NmB-polyST by QuickChange site-directed mutagenesis. Vmax value for CMP-Neu5Ac is decreased by a factor 6 with respect to the wild-type enzyme and the Km value for CMP-Neu5Ac is 5fold
P279A
-
nearly inactive, single-point mutation of NmB-polyST by QuickChange site-directed mutagenesis. Vmax value for CMP-Neu5Ac is decreased by a factor of 4 with respect to the wild-type enzyme and the Km values for CMP-Neu5Ac is increased 3fold
DELTA32I53S
-
truncated mutant. In addition to the alpha2,3- and alpha2,8-sialyltransferase activities of wild-type for the synthesis of GM3- and GD3-type oligosaccharides, respectively. The CstII DELTA32I53S mutant has alpha2,8-sialyltransferase, i. e. GT3 oligosaccharide synthase activity for the synthesis of GT3 oligosaccharide. It also has alpha2,8-sialidase i.e. GD3 oligosaccharide sialidase activity that catalyzes the specific cleavage of the alpha2,8-sialyl linkage of GD3-type oligosaccharides and alpha2,8-trans-sialidase, i. e. GD3 oligosaccharide trans-sialidase activity that catalyzes the transfer of a sialic acid from a GD3 oligosaccharide to a different GM3 oligosaccharide
additional information
B0CN48, -
morpholino knock-down of St8SiaIII leads to anomalous somite morphologies, including defects in segment boundary formation and myotendious-junction integrity
additional information
-
construction of fusion proteins of polysialyltransferase enzyme with the bifunctional alpha-2,3/alpha-2,8-sialyltransferase from Campylobacter jejuni to create self priming polysialyltransferases. The bifunctional sialyltransferase utilizes various synthetic disaccharide acceptors with a terminal galactose
H331K
Q92187
catalytically inactive
additional information
-
overexpression of GD3 synthase in Chang liver cells increases the expression of the microsomal triglyceride transfer protein gene, but GM3 synthase-transfected cells do not. The levels of GM3 and GD3 gangliosides in each of the transfected cells are increased in the cell extract as well as the medium. In addition, GD3 synthase-transfected cells show an increased secretion of triglyceride-enriched apoB. In contrast, the triglyceride content in GM3 synthase-transfected cells is relatively lower. Treatment with small interfering RNAs and GD3 antibody decreases apoB secretion
additional information
-
transfection of K-562 cells with GD3 synthase gene results in specific increase in membrane transglutaminase 2 protein and accelerate the erythroid differentiation. Treatment with GD3 synthase small interfering RNA results in decrease of membrane transglutaminase 2 protein
M326F
Q64687, Q8K4T1
the mutant of isoform ST8Sia-VI shows no activity with bovine submaxillary mucin
additional information
-
examination of amyloid beta-ganglioside interactions in neural tissue from mice lacking the gene coding for GD3 synthase, St8sia1, and in a double-transgenic mouse model of Alzheimer’s disease mutated in amyloid precursor protein APP and presenilin PSEN1 cross-bred with GD3 synthase deficient mice. In primary neurons and astrocytes lacking GD3S, amyloid beta-induced cell death and amyloid beta aggregation are inhibited. Like GD3 synthase eficient and APP/PSEN1 double-transgenic mice, APP/PSEN1/GD3 synthase deficient triple-mutant mice are indistinguishable from wild-type mice on casual examination. APP/PSEN1 double-transgenics exhibit robust impairments on a number of reference-memory tasks. In contrast, APP/PSEN1/GD3 synthase deficient triple-mutant mice perform as well as wild-type control and GD3-synthase deficient mice. Consistent with the behavioral improvements, both aggregated and unaggregated amyloid beta and associated neuropathology are almost completely eliminated in triple-mutant mice
additional information
-
study on electrophysiological parameters of synaptic transmission at the neuromuscular junction ex vivo of a GD3 synthase knockout mouse, expressing only the O- and a-series gangliosides, as well as of a GM2/GD2-synthase*GD3-synthase double-knockout mouse, lacking all gangliosides except GM3. No major synaptic deficits are found in either null-mutant. Some extra degree of rundown of acetylcholine release at high intensity use is present at the dKO NMJ and a temperature-specific increase in acetylcholine release at 35°C is observed in GD3-synthase knockout neuromuscular junctions, compared with wild-type
H278A/P279A
-
the H278A and P279A mutants maintain residual activity (below 10% of wild type), when both residues are changed to alanine simultaneously (H278A/P279A) enzyme activity is abolished
additional information
-
construction of fusion proteins of polysialyltransferase enzyme with the bifunctional alpha-2,3/alpha-2,8-sialyltransferase from Campylobacter jejuni to create self priming polysialyltransferases. The bifunctional sialyltransferase utilizes various synthetic disaccharide acceptors with a terminal galactose and can be used to create polysialic acid on O-linked glycopeptides
additional information
-
mutational analysis of NmBpolyST, emphasized by structural data available for the Pasteurella multocida sialyltransferase PmST1, functional importance of the two functional motifs for enzyme catalysis and CMP-Neu5Ac binding shown; removal of 23 (DELTA23NmBpolyST) and 33 (DELTA33NmB-polyST) amino acids from the N-terminus has only slight effects on solubility and activity of NmB-polyST. Deletion of the first 64 amino acids (DELTA64NmB-polyST) shifts the majority of the expressed protein to the insoluble fraction and no enzymatic activity is detected in soluble or insoluble fractions. Truncated NmBpolySTs lacking the C-terminal domain either partially (NmB-polySTDELTA22, NmB-polySTDELTA60) or completely (NmB-polySTDELTA94, NmB-polySTDELTA95, NmB-polySTDELTA97): each C-terminal truncation completely abolished enzymatic activity
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
diagnostics
-
putative prognostic marker in breast cancer, estrogen receptor negative patients with high ceramide kinase expression had a worse prognosis then those with low expression
medicine
-
enzyme has an apoptotic effect on ECV304 cells through downregulation of B-cll/CLL lymphoma 2 expression via dephosphorylation of AKT and cyclic-AMP responsive element binding protein
medicine
-
enhancing effects of enzyme on proliferation or mobility are differential depending on the cell type
medicine
-
plasma membrane associated gangliosides GD3 play important roles in apoB secretion, and an enhancement in GD3 levels might be a risk factor for the development of atherosclerosis by increasing the secretion of triglyceride-enriched apoB containing lipoproteins
medicine
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examination of amyloid beta-ganglioside interactions in neural tissue from mice lacking the gene coding for GD3 synthase, St8sia1, and in a double-transgenic mouse model of Alzheimer’s disease mutated in amyloid precursor protein APP and presenilin PSEN1 cross-bred with GD3 synthase deficient mice. In primary neurons and astrocytes lacking GD3 synthase, amyloid beta-induced cell death and amyloid beta aggregation are inhibited. Like GD3 synthase eficient and APP/PSEN1 double-transgenic mice, APP/PSEN1/GD3 synthase deficient triple-mutant mice are indistinguishable from wild-type mice on casual examination. APP/PSEN1 double-transgenics exhibit robust impairments on a number of reference-memory tasks. In contrast, APP/PSEN1/GD3 synthase deficient triple-mutant mice perform as well as wild-type control and GD3-synthase deficient mice. Consistent with the behavioral improvements, both aggregated and unaggregated amyloid beta and associated neuropathology are almost completely eliminated in triple-mutant mice
drug development
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basis for design of sialyltransferase-specific drugs