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Information on EC 2.8.2.8 - [heparan sulfate]-glucosamine N-sulfotransferase and Organism(s) Mus musculus and UniProt Accession P52850

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IUBMB Comments
The enzyme also catalyses the sulfation of chondroitin 4-sulfate and dermatan sulfate, but to a much more limited extent.
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Select one or more organisms in this record:
This record set is specific for:
Mus musculus
UNIPROT: P52850
Word Map
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
Synonyms
3'-phosphoadenylyl-sulfate:heparitin N-sulfotransferase, 3'-phosphoadenylylsulfate:N-desulfoheparin N-sulfotransferase, 3'-phosphoadenylylsulfate:N-desulfoheparin sulfotransferase, desulfoheparin sulfotransferase, EC 2.8.2.12, GlcNAc N-deacetylase/GlcN N-sulfotransferase, GlcNAc N-deacetylase/GlcN N-sulfotransferase 1, GlcNAc N-deacetylase/N-sulfotransferase, glucosaminyl N-deacetylase/N-sulfotransferase, heparan sulfate 2-N-sulfotransferase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3'-phosphoadenylyl-sulfate:heparitin N-sulfotransferase
-
-
-
-
3'-phosphoadenylylsulfate:N-desulfoheparin N-sulfotransferase
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-
-
-
3'-phosphoadenylylsulfate:N-desulfoheparin sulfotransferase
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-
-
-
desulfoheparin sulfotransferase
-
-
-
-
GlcNAc N-deacetylase/GlcN N-sulfotransferase
272983, 272987, 272988, 272989
-
GlcNAc N-deacetylase/GlcN N-sulfotransferase 1
244
-
glucosaminyl N-deacetylase/N-sulfotransferase
heparan sulfate 2-N-sulfotransferase
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-
-
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heparan sulfate N-deacetylase/N-sulfotransferase
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-
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heparan sulfate N-sulfotransferase
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-
-
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heparan sulfate sulfotransferase
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-
-
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heparin N-sulfotransferase
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-
-
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heparitin sulfotransferase
-
-
-
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N-acetylglucosamine N-deacetylase/N-sulfotransferase
244
-
N-deacetylase-N-sulfotransferase-1
244
-
N-deacetylase/N-sulfotransferase
244
-
N-deacetylase/N-sulfotransferase-1
244
-
N-deacetylase/N-sulfotransferase-2
N-desulfoheparin sulfotransferase
-
-
-
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N-heparan sulfate sulfotransferase
-
-
-
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N-HSST
-
-
-
-
NDST-1
244
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NDST-2
244
-
Ndst1
NDST2
PAPS:DSH sulfotransferase
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-
-
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PAPS:N-desulfoheparin sulfotransferase
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-
-
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sulfotransferase, desulfoheparin
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
sulfate group transfer
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-
-
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PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
3'-phosphoadenylyl-sulfate:[heparan sulfate]-glucosamine N-sulfotransferase
The enzyme also catalyses the sulfation of chondroitin 4-sulfate and dermatan sulfate, but to a much more limited extent.
CAS REGISTRY NUMBER
COMMENTARY hide
9026-75-9
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3'-phosphoadenylyl sulfate + heparosan
adenosine 3',5'-bisphosphate + heparosan sulfate
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine
show the reaction diagram
3'-phosphoadenylylsulfate + N-desulfated heparin
?
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + heparosan
adenosine 3',5'-bisphosphate + heparosan sulfate
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-D-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfo-D-glucosamine
show the reaction diagram
-
-
-
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-D-sulfoglucosamine
show the reaction diagram
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine
show the reaction diagram
3'-phosphoadenylylsulfate + chondroitin 4-sulfate
?
show the reaction diagram
-
weak activity
-
-
?
3'-phosphoadenylylsulfate + dermatan sulfate
?
show the reaction diagram
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weak activity
-
-
?
3'-phosphoadenylylsulfate + heparan sulfate
adenosine 3',5'-bisphosphate + N-sulfoheparan sulfate
show the reaction diagram
-
-
-
-
?
3'-phosphoadenylylsulfate + heparin
adenosine 3',5'-bisphosphate + N-sulfoheparin
show the reaction diagram
-
-
-
-
?
3'-phosphoadenylylsulfate + N-acetylated heparan sulfate
?
show the reaction diagram
-
-
-
-
?
3'-phosphoadenylylsulfate + N-deacetylated K5 polysaccharide
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
-
-
-
-
?
3'-phosphoadenylylsulfate + N-deacetylated K5-polysaccharide
?
show the reaction diagram
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from E. coli K5-derived capsular polysaccharide
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-
?
3'-phosphoadenylylsulfate + N-desulfated heparin
?
show the reaction diagram
3'-phosphoadenylylsulfate + N-desulfoheparin
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
-
-
-
-
?
additional information
?
-
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
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine
show the reaction diagram
P52850
-
-
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-D-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfo-D-glucosamine
show the reaction diagram
-
-
-
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-D-sulfoglucosamine
show the reaction diagram
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine
show the reaction diagram
3'-phosphoadenylylsulfate + N-desulfoheparin
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
-
-
-
-
?
additional information
?
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-
heparan sulfate Ndst1 gene function variably regulates multiple signaling pathways during mouse development, disruption of heparan sulfate synthesis in vertebrate development causes malformations that are composites of those caused by mutations of multiple heparan sulfate binding growth factors and morphogens, overview, molecular mechanisms leading to frontonasal dysplasia, impaired spinal and cranial neural tube fusion, and skeletal abnormalities in Ndst1 mutant embryos, impaired fibroblast growth factor, Hedgehog, and Wnt function may contribute to some of these phenotypes, overview
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
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can partially replace Mn2+ in activation
Mn2+
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10 mM, 4 to 5fold activation; divalent cation required; Mn2+ most effective
additional information
-
greatest activity in presence of sodium phosphate buffer, in imidazole-HCl reaction rate is lower
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
CNMQALSMPVTC
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the peptide inhibits isoform Ndst1 activity by direct interaction with the enzyme near the active site, the peptide inhibits sulfotransferase activity by 25 and 40% at 0.01 and 0.1 mM, respectively
CRGWRGEKIGNC
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the peptide blocks the binding of substrate to the enzyme isoform Ndst1
Cu2+
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NaCl
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0.125 M
NMQALSMPVT
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PCMB
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phenylmercuric acetate
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RGWRGEKIGN
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Zn2+
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
heparin sulfate
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excess heparin sulfate increases the N-sulfotransferase activity of heparin sulfate-modifying N-deacetylase/N-sulfotransferase
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.02 - 0.108
3'-phosphoadenylylsulfate
0.0009 - 0.0224
N-deacetylase K5-polysaccharide
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0.013
N-desulfoheparin
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apparent value, in 50 mM HEPES, pH 7.0, at 37°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.14
NMQALSMPVT
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apparent value, in 50 mM HEPES, pH 7.0, at 37°C
0.48
RGWRGEKIGN
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apparent value, in 50 mM HEPES, pH 7.0, at 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.3
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assay at
6.7 - 7.2
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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NDST-2 correlates strongly with mast cell maturation, whereas the expression of the NDST-1 isoform is approximately equal at all stages of maturation. NDST-2 correlates strongly with mast cell maturation, whereas the expression of the NDST-1 isoform is approximately equal at all stages of maturation. NDST-1 expression is detected already in the early stage, day 0, bone marrow cells, but the level of expression does not increase throughout the process of mast cell maturation. NDST-2 expression follows an entirely different pattern, with low expression in day 0 and day 7 cultures, followed by a markedly increased level of expression starting from day 14 and has a continuously increased expression throughout the entire culture period. NDST-2 is downregulated after mast cell activation
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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gene Ndst1 is expressed during lens development, in lens epithelium, strong expression occurs in both the lens placode and in the optic vesicle in mouse embryos at stage E9.5, overview
Manually annotated by BRENDA team
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embryonic
Manually annotated by BRENDA team
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NDST-2 correlates strongly with mast cell maturation, whereas the expression of the NDST-1 isoform is approximately equal at all stages of maturation. NDST-1 expression is detected already in the early stage, day 0, bone marrow cells, but the level of expression does not increase throughout the process of mast cell maturation. NDST-2 expression follows an entirely different pattern, with low expression in day 0 and day 7 cultures, followed by a markedly increased level of expression starting from day 14 and has a continuously increased expression throughout the entire culture period. NDST-2 is downregulated after mast cell activation
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
localized to the medial- or trans-Golgi network
Manually annotated by BRENDA team
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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the absence of both isoforms Ndst1 and Ndst2 induces increased branching of the ductal epithelium in mammary gland. Ndst-deficient ducts display an apparent overabundance of branched ductal epithelia and cellular chimerism in the level of sulfated cell surface heparan sulfate
metabolism
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NDST-2 is the first and a key enzyme in heparin synthesis, with the following modifications being dependent on the reactions catalyzed by the NDSTs
physiological function
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NDSTs have key regulatory functions in determining the degree of heparin/heparan sulfate sulfation. NDST-2 has a role in the formation of fully sulfated heparin attached to the serglycin core protein
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
NDST2_MOUSE
883
1
101202
Swiss-Prot
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40
-
2 min, no effect
50
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1 min, 15% loss of activity
85
-
2 min, complete loss of activity
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-18°C, stable for at least 4 months
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PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
IgG-Sepharose bead chromatography
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CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
expressed in HEK-293 cells
isozyme NDST2, DNA sequence determination and analysis
DNA sequence determination and analysis, genetic structure and organization
expressed in pgsA745 cells
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expression in Saccharomyces cerevisiae
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isozyme NDST1, DNA sequence determination and analysis
isozyme NDST3, DNA sequence determination and analysis
isozyme NDST4, DNA sequence determination and analysis
overexpression of isozymes NDST1 and NDST2 in human kidney cells 293; stable functional overexpression in human kidney cell line 293, 2.5fold increase in N-sulfation and 8fold increase of N-deacetylation of glucosaminyl residues of human heparan sulfate in transfected cells
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stable functional overexpression in human kidney cell line 293, 2.5fold increase in N-sulfation and 8fold increase of N-deacetylation of glucosaminyl residues of human heparan sulfate in transfected cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
NDST-2 is downregulated after mast cell activation, e.g. by calcium ionophore or IgE ligation. Down-regulation of NDST-2 gene by A23187
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
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NDST-2 expression is a late differentiation marker for mast cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Cheung, W.F.; Eriksson, I.; Kusche-Gulberg, M.; Lindahl, U.; Kjellen, L.
Expression of mouse mastocytoma glucosaminyl N-deacetylase/N-sulfotransferase in human kidney 293 cells results in increased N-sulfation of heparan sulfate
Biochemistry
35
5250-5256
1996
Mus musculus
Manually annotated by BRENDA team
Orellana, A.; Hirschberg, C.B.; Wei, Z.; Swiedler, S.J.; Ishihara, M.
Molecular cloning and expression of a glycosaminoglycan N-acetylglucosaminyl N-deacetylase/N-sulfotransferase from a heparin-producing cell line
J. Biol. Chem.
269
2270-2276
1994
Mus musculus
Manually annotated by BRENDA team
Eisenman, R.A.; Balasubramanian, A.S.; Marx, W.
3-Phosphoadenylylsulfate:N-desulfoheparin sulfotransferase associated with a postmicrosomal particulate mastocytoma fraction
Arch. Biochem. Biophys.
119
387-397
1967
Mus musculus
Manually annotated by BRENDA team
Jansson, L.; Höök, M.; Wasteson, A.; Lindahl, U.
Biosynthesis of heparin. Solubilization and partial characterization of N- and O-sulphotransferases
Biochem. J.
149
49-55
1975
Mus musculus
Manually annotated by BRENDA team
Kusche-Gullberg, M.; Eriksson, I.; Pikas, D.S.; Kjellen, L.
Identification and expression in mouse of two heparan sulfate glucosaminyl N-deacetylase/N-sulfotransferase genes
J. Biol. Chem.
273
11902-11907
1998
Mus musculus, Mus musculus (Q3UHN9), Rattus norvegicus
Manually annotated by BRENDA team
Aikawa, J.; Grobe, K.; Tsujimoto, M.; Esko, J.D.
Multiple isozymes of heparan sulfate/heparin GlcNAc N-deacetylase/GlcN N-sulfotransferase. Structure and activity of the fourth member, NDST4
J. Biol. Chem.
276
5876-5882
2001
Homo sapiens, Homo sapiens (O95803), Homo sapiens (Q9H3R1), Mus musculus, Mus musculus (P52850), Mus musculus (Q3UHN9), Mus musculus (Q9EQH7), Mus musculus (Q9EQW8)
Manually annotated by BRENDA team
Grobe, K.; Ledin, J.; Ringvall, M.; Holmborn, K.; Forsberg, E.; Esko, J.D.; Kjellen, L.
Heparan sulfate and development: differential roles of the N-acetylglucosamine N-deacetylase/N-sulfotransferase isozymes
Biochim. Biophys. Acta
1573
209-215
2002
Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Homo sapiens (O95803), Homo sapiens (Q9H3R1), Mus musculus, Mus musculus (Q9EQW8), vertebrata
Manually annotated by BRENDA team
Grobe, K.; Inatani, M.; Pallerla, S.R.; Castagnola, J.; Yamaguchi, Y.; Esko, J.D.
Cerebral hypoplasia and craniofacial defects in mice lacking heparan sulfate Ndst1 gene function
Development
132
3777-3786
2005
Mus musculus
Manually annotated by BRENDA team
Yabe, T.; Hata, T.; He, J.; Maeda, N.
Developmental and regional expression of heparan sulfate sulfotransferase genes in the mouse brain
Glycobiology
15
982-993
2005
Mus musculus
Manually annotated by BRENDA team
Pallerla, S.R.; Pan, Y.; Zhang, X.; Esko, J.D.; Grobe, K.
Heparan sulfate Ndst1 gene function variably regulates multiple signaling pathways during mouse development
Dev. Dyn.
236
556-563
2007
Mus musculus
Manually annotated by BRENDA team
Pan, Y.; Woodbury, A.; Esko, J.D.; Grobe, K.; Zhang, X.
Heparan sulfate biosynthetic gene Ndst1 is required for FGF signaling in early lens development
Development
133
4933-4944
2006
Mus musculus
Manually annotated by BRENDA team
Ledin, J.; Ringvall, M.; Thuveson, M.; Eriksson, I.; Wilen, M.; Kusche-Gullberg, M.; Forsberg, E.; Kjellen, L.
Enzymatically active N-deacetylase/N-sulfotransferase-2 is present in liver but does not contribute to heparan sulfate N-sulfation
J. Biol. Chem.
281
35727-35734
2006
Mus musculus
Manually annotated by BRENDA team
Duelli, A.; Roennberg, E.; Waern, I.; Ringvall, M.; Kolset, S.O.; Pejler, G.
Mast cell differentiation and activation is closely linked to expression of genes coding for the serglycin proteoglycan core protein and a distinct set of chondroitin sulfate and heparin sulfotransferases
J. Immunol.
183
7073-7083
2009
Mus musculus
Manually annotated by BRENDA team
Holley, R.J.; Deligny, A.; Wei, W.; Watson, H.A.; Ninonuevo, M.R.; Dagaelv, A.; Leary, J.A.; Bigger, B.W.; Kjellen, L.; Merry, C.L.
Mucopolysaccharidosis type I, unique structure of accumulated heparan sulfate and increased N-sulfotransferase activity in mice lacking alpha-L-iduronidase
J. Biol. Chem.
286
37515-37524
2011
Mus musculus
Manually annotated by BRENDA team
Gesteira, T.F.; Coulson-Thomas, V.J.; Taunay-Rodrigues, A.; Oliveira, V.; Thacker, B.E.; Juliano, M.A.; Pasqualini, R.; Arap, W.; Tersariol, I.L.; Nader, H.B.; Esko, J.D.; Pinhal, M.A.
Inhibitory peptides of the sulfotransferase domain of the heparan sulfate enzyme, N-deacetylase-N-sulfotransferase-1
J. Biol. Chem.
286
5338-5346
2011
Mus musculus
Manually annotated by BRENDA team
Bush, K.T.; Crawford, B.E.; Garner, O.B.; Nigam, K.B.; Esko, J.D.; Nigam, S.K.
N-sulfation of heparan sulfate regulates early branching events in the developing mammary gland
J. Biol. Chem.
287
42064-42070
2012
Mus musculus
Manually annotated by BRENDA team
Deligny, A.; Dierker, T.; Dagaelv, A.; Lundequist, A.; Eriksson, I.; Nairn, A.V.; Moremen, K.W.; Merry, C.L.; Kjellen, L.
NDST2 (N-deacetylase/N-sulfotransferase-2) enzyme regulates heparan sulfate chain length
J. Biol. Chem.
291
18600-18607
2016
Mus musculus, Mus musculus (P52850)
Manually annotated by BRENDA team
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