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bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1; glucosaminyl N-deacetylase/N-sulfotransferase 1; NDST-1; [heparan sulfate]-glucosamine N-sulfotransferase 1; HSNST 1; N-heparan sulfate sulfotransferase 1; N-HSST 1 [includes: heparan sulfate N-deacetylase 1; heparan sulfate N-sulfotransferase 1] (NDST1, HSST, HSST1)
Function:
- essential bifunctional enzyme
- catalyzes both N-deacetylation & N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate
- modifies the GlcNAc-GlcA dissacharide repeating sugar backbone to make N-sulfated heparosan, a prerequisite substrate for later modifications in heparin biosynthesis
- plays a role in determining the extent & pattern of sulfation of heparan sulfate
- role in biosynthesis of heparan sulfate that can ultimately serve as L- selectin ligands, thereby playing a role in inflammatory response
- glycan metabolism; heparan sulfate biosynthesis
- glycan metabolism; heparin biosynthesis
3'-phosphoadenylyl sulfate + [heparansulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine
Kinetic parameters:
- KM=13.3 uM for K5 polysaccharide
- KM=0.35 uM for N-acetylated HS-II
Structure:
- monomer
- belongs to the sulfotransferase 1 family, NDST subfamily
Compartment: Golgi membrane s
Alternative splicing: named isoforms=2
Expression:
- widely expressed
- most abundant in heart, liver & pancreas
Notes:
- the presence of 4 different heparan sulfate N-deacetylase/N-sulfotransferase enzymes in mammals, as well as differences in their enzyme activity suggest that some initiate heparan sulfate modification/ sulfation reactions, whereas others later on fill in or extend already modified heparan sulfate sequences
General
glycoprotein
membrane protein
sulfotransferase
Properties
SIZE: entity length = 882 aa
MW = 101 kD
COMPARTMENT: golgi
MOTIF: transmembrane domain {18-39}
Heparan sulfate N-deacetylase 1 {40-598}
MOTIF: N-glycosylation site {N231}
N-glycosylation site {N351}
N-glycosylation site {N401}
Heparan sulfate N-sulfotransferase 1 {599-882}
MOTIF: lysine residue {K614}
N-glycosylation site {N667}
binding site
SITE: 712-712
FOR-BINDING-OF: 3'-phosphoadenosine-5'-phosphosulfate
cysteine residue {C818}
MODIFICATION: cysteine residue {C828}
cysteine residue {C828}
MODIFICATION: cysteine residue {C818}
Database Correlations
OMIM 600853
UniProt P52848
Pfam PF00685
Entrez Gene 3340
Kegg hsa:3340
ENZYME 2.8.2.8
References
- UniProt :accession P52848
- GGDB; Glycogene database
http://riodb.ibase.aist.go.jp/rcmg/ggdb/