Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1

Contribute

Send feedback

Read comments (?) or add your own

Q02353 (NDST1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 92. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1
EC=2.8.2.8

Alternative name(s):
Glucosaminyl N-deacetylase/N-sulfotransferase 1
Short name=NDST-1
N-heparan sulfate sulfotransferase 1
Short name=N-HSST 1
[Heparan sulfate]-glucosamine N-sulfotransferase 1
Short name=HSNST 1

Including the following 2 domains:

Heparan sulfate N-deacetylase 1
EC=3.-.-.-
Heparan sulfate N-sulfotransferase 1
EC=2.8.2.-

Gene names

Name:	Ndst1
Synonyms:	Hsst, Hsst1, Ndanst

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	882 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Essential bifunctional enzyme that catalyzes both the N-deacetylation and the 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 and pattern of sulfation of heparan sulfate. Compared to other NDST enzymes, its presence is absolutely required. Participates in biosynthesis of heparan sulfate that can ultimately serve as L-selectin ligands, thereby playing a role in inflammatory response.
Catalytic activity	3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine = adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine.
Pathway	Glycan metabolism; heparan sulfate biosynthesis. Glycan metabolism; heparin biosynthesis.
Subunit structure	Monomer By similarity.
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein Ref.4.
Miscellaneous	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 other later on fill in or extend already modified heparan sulfate sequences.
Sequence similarities	Belongs to the sulfotransferase 1 family. NDST subfamily.
Biophysicochemical properties	Kinetic parameters: K_M=144 µM for K5 polysaccharide (for deacetylase activity) Ref.3 K_M=160 µM for K5 polysaccharide (for sulfotransferase activity) V_max=40 µmol/min/mg enzyme with K5 polysaccharide as substrate (for deacetylase activity) V_max=2104 µmol/min/mg enzyme with K5 polysaccharide as substrate (for sulfotransferase activity)

Ontologies

Keywords
Biological process	Inflammatory response
Cellular component	Golgi apparatus Membrane
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Hydrolase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	[heparan sulfate]-glucosamine N-sulfotransferase activity Inferred from electronic annotation. Source: EC hydrolase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 882

882

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1

PRO_0000085211

Regions

Topological domain

1 – 17

Cytoplasmic Potential

Transmembrane

18 – 39

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

40 – 882

843

Lumenal Potential

Nucleotide binding

614 – 618

PAPS By similarity

Nucleotide binding

833 – 837

PAPS By similarity

Region

40 – 598

559

Heparan sulfate N-deacetylase 1

Region

599 – 882

284

Heparan sulfate N-sulfotransferase 1

Sites

Active site

614

For sulfotransferase activity By similarity

Binding site

712

PAPS By similarity

Amino acid modifications

Glycosylation

231

N-linked (GlcNAc...) Potential

Glycosylation

351

N-linked (GlcNAc...) Potential

Glycosylation

401

N-linked (GlcNAc...) Potential

Glycosylation

667

N-linked (GlcNAc...) Potential

Disulfide bond

818 ↔ 828

By similarity

Experimental info

Mutagenesis

C → A: Induces a reduction in sulfotransferase activity but does not affect deacetylase activity. Ref.3

Mutagenesis

159

C → A: Induces a reduction in sulfotransferase activity but increases deacetylase activity. Ref.3

Mutagenesis

486

C → A or V: Does not affect sulfotransferase activity but increases deacetylase activity. Ref.3

Mutagenesis

486

C → F: Does not affect sulfotransferase activity but strongly decreases deacetylase activity. Ref.3

Mutagenesis

486

C → G: Does not affect sulfotransferase activity but weakly affects deacetylase activity. Ref.3

Mutagenesis

486

C → R or W: Does not affect sulfotransferase activity but abolishes deacetylase activity. Ref.3

Mutagenesis

586

C → A: Loss of deacetylase and sulfotransferase activities. Ref.3

Mutagenesis

601

C → A: Loss of sulfotransferase activity but does not affect deacetylase activity. Ref.3

Mutagenesis

751

C → A: Does not affect neither deacetylase nor sulfotransferase activities. Ref.3

Mutagenesis

818

C → A: Loss of sulfotransferase activity but does not affect deacetylase activity. Ref.3

Mutagenesis

828

C → A: Loss of sulfotransferase activity but does not affect deacetylase activity. Ref.3

Sequences

Sequence

Length

Mass (Da)

Tools

Q02353 [UniParc].

Last modified July 1, 1993. Version 1.
Checksum: F3AB9263EF6E4345
Show »

FASTA

882

100,785

        10         20         30         40         50         60 
MPALACLRRL CRHLSPQAVL FLLFVFCLFS VFVSAYYLYG WNRGLEPSAD ASESDCGDPP 

        70         80         90        100        110        120 
PVAPSRLLPI KPVQAVAPSR TDPLVLVFVE SLYSQLGQEV VAILESSRFK YRTEIAPGKG 

       130        140        150        160        170        180 
DMPTLTDKGR GRFALIIYEN ILKYVNLDAW NRELLDKYCV AYGVGIIGFF KANENSLLSA 

       190        200        210        220        230        240 
QLKGFPLFLH SNLGLKDCSI NPKSPLLYVT RPSEVEKGVL PGEDWTVFQS NHSTYEPVLL 

       250        260        270        280        290        300 
AKTRSSESIP HLGADAGLHA ALHATVVQDL GLHDGIQRVL FGNNLNFWLH KLVFVDAVAF 

       310        320        330        340        350        360 
LTGKRLSLPL DRYILVDIDD IFVGKEGTRM KVEDVKALFD TQNELRTHIP NFTFNLGYSG 

       370        380        390        400        410        420 
KFFHTGTDAE DAGDDLLLSY VKEFWWFPHM WSHMQPHLFH NQSVLAEQMA LNKKFAVEHG 

       430        440        450        460        470        480 
IPTDMGYAVA PHHSGVYPVH VQLYEAWKQV WNIRVTSTEE YPHLKPARYR RGFIHNGIMV 

       490        500        510        520        530        540 
LPRQTCGLFT HTIFYNEYPG GSSELDKIIN GGELFLTVLL NPISVFMTHL SNYGNDRLGL 

       550        560        570        580        590        600 
YTFKHLVRFL HSWTNLRLQT LPPVQLAQKY FQIFSEEKDP LWQDPCEDKR HKDIWSKEKT 

       610        620        630        640        650        660 
CDRFPKLLII GPQKTGTTAL YLFLGMHPDL SSNYPSSETF EEIQFFNGHN YHKGIDWYME 

       670        680        690        700        710        720 
FFPIPSNTTS DFYFEKSANY FDSEVAPRRA AALLPKAKVL TILINPADRA YSWYQHQRAH 

       730        740        750        760        770        780 
DDPVALKYTF HEVITAGPDA SSKLRALQNR CLVPGWYATH IERWLSAFHA NQILVLDGKL 

       790        800        810        820        830        840 
LRTEPAKVMD TVQKFLGVTS TVDYHKTLAF DPKKGFWCQL LEGGKTKCLG KSKGRKYPEM 

       850        860        870        880 
DLDSRAFLKD YYRDHNIELS KLLYKMGQTL PTWLREDLQN TR

« Hide

References

[1]	"Molecular cloning and expression of rat liver N-heparan sulfate sulfotransferase." Hashimoto Y., Orellana A., Gil G., Hirschberg C.B. J. Biol. Chem. 267:15744-15750(1992) [PubMed: 1379236] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[2]	"A single protein catalyzes both N-deacetylation and N-sulfation during the biosynthesis of heparan sulfate." Wei Z., Swiedler S.J., Ishihara M., Orellana A., Hirschberg C.B. Proc. Natl. Acad. Sci. U.S.A. 90:3885-3889(1993) [PubMed: 8483907] [Abstract] Cited for: CHARACTERIZATION.
[3]	"Functional analysis of conserved cysteines in heparan sulfate N-deacetylase-N-sulfotransferases." Wei Z., Swiedler S.J. J. Biol. Chem. 274:1966-1970(1999) [PubMed: 9890952] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF CYS-56; CYS-159; CYS-486; CYS-586; CYS-601; CYS-751; CYS-818 AND CYS-828.
[4]	"Immunopurification of Golgi vesicles by magnetic sorting." Mura C.V., Becker M.I., Orellana A., Wolff D. J. Immunol. Methods 260:263-271(2002) [PubMed: 11792394] [Abstract] Cited for: SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M92042 mRNA. Translation: AAA41701.1.
IPI	IPI00206014.
PIR	A42855.
RefSeq	NP_077337.1. NM_024361.1.
UniGene	Rn.9705.
3D structure databases
ProteinModelPortal	Q02353.
SMR	Q02353. Positions 579-879.
ModBase	Search...
Protein-protein interaction databases
STRING	Q02353.
Proteomic databases
PRIDE	Q02353.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000025881; ENSRNOP00000025881; ENSRNOG00000019014.
GeneID	29633.
KEGG	rno:29633.
UCSC	NM_024361. rat.
Organism-specific databases
CTD	3340.
RGD	69303. Ndst1.
Phylogenomic databases
eggNOG	maNOG05161.
GeneTree	ENSGT00560000076777.
HOVERGEN	HBG082011.
InParanoid	Q02353.
OrthoDB	EOG48KR9J.
Gene expression databases
ArrayExpress	Q02353.
Genevestigator	Q02353.
GermOnline	ENSRNOG00000019014. Rattus norvegicus.
Family and domain databases
InterPro	IPR021930. Heparan_SO4_deacetylase. IPR000863. Sulfotransferase_dom. [Graphical view]
KO	K02576.
Pfam	PF12062. HSNSD. 1 hit. PF00685. Sulfotransfer_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	609868.

Entry information

Entry name

NDST1_RAT

Accession

Primary (citable) accession number: Q02353

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	July 1, 1993
Last modified:	December 14, 2011
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Including the following 2 domains:

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents