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Information on EC 2.4.99.8 - alpha-N-acetylneuraminate alpha-2,8-sialyltransferase and Organism(s) Homo sapiens and UniProt Accession Q92185

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IUBMB Comments
Gangliosides act as acceptors.
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This record set is specific for:
Homo sapiens
UNIPROT: Q92185
Word Map
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The taxonomic range for the selected organisms is: Homo sapiens
Synonyms
alpha-2,8-polysialyltransferase, alpha-2,8-PST, alpha-2,8-sialyltransferase, alpha-2,8-sialyltransferase 8A, alpha2,8-sialyltransferase, alpha2,8S-T, CMP-N-acetylneuraminate: N-acetyl-neuraminyl-D-galactosyl-D-glucosylceramide N-acetylneuraminyl alpha2->8 transferase, CMP-NAcNeu:GM3 ganglioside sialyltransferase, CMP-NeuAc:GD3(alpha 2-8) sialyltransferase, CMP-NeuAc:GM3 alpha 2,8-sialyltransferase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
alpha-2,8-sialyltransferase
alpha-2,8-sialyltransferase 8A
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-
-
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CMP-NAcNeu:GM3 ganglioside sialyltransferase
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-
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CMP-NeuAc:GD3(alpha 2-8) sialyltransferase
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-
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CMP-NeuAc:LM1(alpha 2-8) sialyltransferase
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CMP-sialic acid:GM3 sialyltransferase
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ganglioside GD3 synthase
ganglioside GD3 synthetase
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-
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ganglioside GD3-synthase
247
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ganglioside GT3 synthase
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-
-
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GD3 synthase
GD3S
284706
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hST8Sia III
247
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polysialyltransferase
298644
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SAT-2
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-
-
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Sia-alpha2,3-Gal-beta1,4-GlcNAc-R:alpha2,8-sialyltransferase
247
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sialyltransferase II
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sialyltransferase, cytidine monophosphoacetylneuraminate-ganglioside GM3
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-
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ST-II
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-
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ST8
247
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ST8Sia1
247
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ST8SIA4
ST8SiaIV
298644
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycosyl group transfer
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-
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SYSTEMATIC NAME
IUBMB Comments
CMP-N-acetylneuraminate:alpha-N-acetylneuraminyl-(2->3)-beta-D-galactoside alpha-(2->8)-N-acetylneuraminyltransferase
Gangliosides act as acceptors.
CAS REGISTRY NUMBER
COMMENTARY hide
67339-00-8
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
CMP-N-acetylneuraminate + ganglioside GM3
CMP + ?
show the reaction diagram
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-
-
-
?
CMP-N-acetylneuraminate + ganglioside GM3
CMP + ganglioside GD3
show the reaction diagram
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
-
-
-
-
?
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
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-
i.e. disialosyllactosylceramide or ganglioside GD3
?
CMP-N-acetylneuraminate + neural cell adhesion molecule
CMP + ?
show the reaction diagram
-
-
-
?
CMP-N-acetylneuraminate + neuropilin-2
CMP + ?
show the reaction diagram
-
-
-
?
additional information
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
CMP-N-acetylneuraminate + ganglioside GM3
CMP + ganglioside GD3
show the reaction diagram
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
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-
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-
?
additional information
?
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
triptolide
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.081 - 0.22
CMP-N-acetylneuraminate
0.083 - 0.979
ganglioside GM3
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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tissue samples of primary invasive breast cancer cases
Manually annotated by BRENDA team
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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
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nuclear factor NF-kappaB plays an essential role in the transcriptional activity of human GD3 synthase gene
Manually annotated by BRENDA team
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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
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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
retention of functional enzyme upon coexpression with calnexin
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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inhibition of the enzyme using small hairpin RNA or triptolide compromises the initiation and maintenance of epithelial-mesenchymal transition instigated by various signaling pathways, including Snail, Twist and transforming growth factor-beta1 as well as the mesenchymal characteristics of claudin-low breast cancer cell lines, SUM159 and MDA-MB-231. Inhibition of enzyme GD3S in vivo prevents metastasis, it inhibits invasion and motility of cancer cells
metabolism
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the enzyme is part of the biosynthetic pathway of glycosphingolipids, overview
physiological function
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GD3 synthase is a critical enzyme involved in GD2 biosynthesis. The enzyme is necessary for wound healing, migration, invasion and stem cell properties in vitro. The enzyme has an important role in the initiation and maintenance of epithelial-mesenchymal transition. Transcription factor FOXC2, a central downstream effector of several epithelial-mesenchymal transition pathways, directly regulates GD3S expression by binding to its promoter. Enzyme GD3S expression correlates with activation of the c-Met signaling pathway leading to increased stem cell properties and metastatic competence
malfunction
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silencing of the ST8SIA4 gene enhances chemosensitivity of K562/ADR cells in vitro and in vivo
metabolism
physiological function
additional information
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direct UVB-irradiation of keratinocytes does not induces melanoma-associated ganglioside GD3 synthase gene in melanocytes, but UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor a and interleukin 6
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
SIA8A_HUMAN
356
1
40519
Swiss-Prot
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50000
x * 50000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 50000, SDS-PAGE
CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
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
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
N188D
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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
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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
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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
H331K
catalytically inactive
additional information
CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
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
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gene ST8SIA1, quantitative enzyme expression analysis, mRNA expressions of glycosyltransferases by qRT-PCR in melanocytes and melanoma lines, overview
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gene ST8SIA1, quantitative reverse-transcription PCR enzyme expression analysis
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cloning and sequence analysis of the 5'-flanking region of human GD3 synthase gene
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expression in K-562 cell
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expression of cDNA from melanoma cell line WM266-4 in Namalwa KJM-1 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression levels are reduced after UVB irradiation in SK-MEL-28 melanoma cells
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GD3 synthase expression is induced by tumor necrosis factor alpha and interleukin 6 in melanocytes, except for SK-MEL-28 cells
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transcription factor FOXC2, a central downstream effector of several epithelial-mesenchymal transition pathways, directly regulates GD3S expression by binding to its promoter
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enzyme transcription is activated during early meso- and endoderm differentiation
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higher expression in estrogen receptor negative breast tumors, gene expression of ganglioside GD3 synthase is associated with prognosis in breast cancer
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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
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
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enzyme expression predicts poor clinical outcome in breast cancer
drug development
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the enzyme can serve as a potential druggable target for inhibiting tumor initiation and metastasis. GD3S expression correlates with activation of the c-Met signaling pathway leading to increased stem cell properties and metastatic competence, the GD3S-c-Met axis might serve as an effective target for the treatment of metastatic breast cancers
diagnostics
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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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Fishman, P.H.; Bradley, R.M.; Henneberry, R.C.
Butyrate-induced glycolipid biosynthesis in HeLa cells: properties of the induced sialyltransferase
Arch. Biochem. Biophys.
172
618-626
1976
Homo sapiens
Manually annotated by BRENDA team
Sasaki, K.; Kurata, K.; Kojima, N.; Kurosawa, N.; Ohta, S.; Hanai, N.; Tsuji, S.; Nishi, T.
Expression cloning of a GM3-specific alpha 2,8-sialyltransferase (GD3 synthase)
J. Biol. Chem.
269
15950-15956
1994
Homo sapiens, Homo sapiens (Q92185)
Manually annotated by BRENDA team
Tomassini, B.; Malisan, F.; Franchi, L.; Nicolo, C.; Calvo, G.B.; Saito, T.; Testi, R.
Calnexin suppresses GD3 synthase-induced apoptosis
FASEB J.
18
1553-1555
2004
Homo sapiens
Manually annotated by BRENDA team
Ha, K.T.; Lee, Y.C.; Kim, C.H.
Overexpression of GD3 synthase induces apoptosis of vascular endothelial ECV304 cells through downregulation of Bcl-2
FEBS Lett.
568
183-187
2004
Homo sapiens
Manually annotated by BRENDA team
Kamimura, Y.; Furukawa, K.; Kittaka, D.; Nishio, M.; Hamamura, K.; Fukumoto, S.
Differential enhancing effects of alpha2,8-sialyltransferase on the cell proliferation and mobility
Int. J. Oncol.
26
337-344
2005
Homo sapiens
Manually annotated by BRENDA team
Wang, Z.; Sun, Z.; Li, A.V.; Yarema, K.J.
Roles for UDP-GlcNAc 2-epimerase/ManNAc 6-kinase outside of sialic acid biosynthesis: modulation of sialyltransferase and BiP expression, GM3 and GD3 biosynthesis, proliferation, and apoptosis, and ERK1/2 phosphorylation
J. Biol. Chem.
281
27016-27028
2006
Homo sapiens
Manually annotated by BRENDA team
Kim, S.; Chung, T.; Jin, U.; Suh, S.; Lee, Y.; Kim, C.
Molecular mechanisms involved in transcriptional activation of the human Sia-alpha2,3-Gal-beta1,4-GlcNAc-R:alpha2,8-sialyltransferase (hST8Sia III) gene induced by KCl in human glioblastoma cells
Biochem. Biophys. Res. Commun.
344
1057-1064
2006
Homo sapiens
Manually annotated by BRENDA team
Kang, N.Y.; Kang, Y.; Kang, S.K.; Lee, Y.C.; Choi, H.J.; Lee, Y.S.; Cho, S.Y.; Kim, Y.S.; Ko, J.H.; Kim, C.H.
Transcriptional regulation of the human GD3 synthase gene expression in Fas-induced Jurkat T cells: a critical role of transcription factor NF-kappaB in regulated expression
Glycobiology
16
375-389
2006
Homo sapiens
Manually annotated by BRENDA team
Kang, S.; Jin, U.; Kim, K.; Lee, Y.; Park, Y.; Kim, C.
Disialoganglioside GD3 increases in the secretion of apoB-containing lipoproteins
Biochem. Biophys. Res. Commun.
356
418-423
2007
Homo sapiens
Manually annotated by BRENDA team
Gu, Y.; Yu, R.K.
Identification and analysis of novel functional sites in human GD3-synthase
Biochem. Biophys. Res. Commun.
370
67-71
2008
Homo sapiens (Q92185)
Manually annotated by BRENDA team
Kang, N.; Kim, C.; Kim, K.; Ko, J.; Lee, J.; Jeong, Y.; Lee, Y.
Expression of the human CMP-NeuAc:GM3 alpha 2,8-sialyltransferase (GD3 synthase) gene through the NF-kB activation in human melanoma SK-MEL-2 cells
Biochim. Biophys. Acta
1769
622-630
2007
Homo sapiens
Manually annotated by BRENDA team
Kang, S.K.; Kim, Y.S.; Kong, Y.J.; Song, K.H.; Chang, Y.C.; Park, Y.G.; Ko, J.H.; Lee, Y.C.; Kim, C.H.
Disialoganglioside GD3 synthase expression recruits membrane transglutaminase 2 during erythroid differentiation of the human chronic myelogenous leukemia K562 cells
Proteomics
8
3317-3328
2008
Homo sapiens
Manually annotated by BRENDA team
Ruckhaeberle, E.; Karn, T.; Rody, A.; Hanker, L.; Gaetje, R.; Metzler, D.; Holtrich, U.; Kaufmann, M.
Gene expression of ceramide kinase, galactosyl ceramide synthase and ganglioside GD3 synthase is associated with prognosis in breast cancer
J. Cancer Res. Clin. Oncol.
135
1005-1013
2009
Homo sapiens
Manually annotated by BRENDA team
Zapater, J.L.; Colley, K.J.
Sequences prior to conserved catalytic motifs of polysialyltransferase ST8Sia IV are required for substrate recognition
J. Biol. Chem.
287
6441-6453
2012
Homo sapiens (Q92187)
Manually annotated by BRENDA team
Miyata, M.; Ichihara, M.; Tajima, O.; Sobue, S.; Kambe, M.; Sugiura, K.; Furukawa, K.; Furukawa, K.
UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor alpha and interleukin 6
Biochem. Biophys. Res. Commun.
445
504-510
2014
Homo sapiens (Q92185)
Manually annotated by BRENDA team
Sarkar, T.R.; Battula, V.L.; Werden, S.J.; Vijay, G.V.; Ramirez-Pena, E.Q.; Taube, J.H.; Chang, J.T.; Miura, N.; Porter, W.; Sphyris, N.; Andreeff, M.; Mani, S.A.
GD3 synthase regulates epithelial-mesenchymal transition and metastasis in breast cancer
Oncogene
34
2958-2967
2015
Homo sapiens, Homo sapiens (Q92185)
Manually annotated by BRENDA team
Zhang, X.; Dong, W.; Zhou, H.; Li, H.; Wang, N.; Miao, X.; Jia, L.
alpha-2,8-Sialyltransferase is involved in the development of multidrug resistance via PI3K/Akt pathway in human chronic myeloid leukemia
IUBMB Life
67
77-87
2015
Homo sapiens
Manually annotated by BRENDA team
Berger, R.P.; Sun, Y.H.; Kulik, M.; Lee, J.K.; Nairn, A.V.; Moremen, K.W.; Pierce, M.; Dalton, S.
ST8SIA4-dependent polysialylation is part of a developmental program required for germ layer formation from human pluripotent stem cells
Stem Cells
34
1742-1752
2016
Homo sapiens
Manually annotated by BRENDA team
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