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P52848 (NDST1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. Heparan sulfate N-deacetylase 1
    EC=3.-.-.-
  2. Heparan sulfate N-sulfotransferase 1
    EC=2.8.2.-
Gene names
Name:NDST1
Synonyms:HSST, HSST1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length882 AA.
Sequence statusComplete.
Protein existenceEvidence 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 disaccharide 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. Ref.6 Ref.7

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.

Subcellular location

Golgi apparatus membrane; Single-pass type II membrane protein Ref.2.

Tissue specificity

Widely expressed. Expression is most abundant in heart, liver and pancreas.

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:

KM=13.3 µM for K5 polysaccharide Ref.7

KM=0.35 µM for N-acetylated HS-II

Ontologies

Keywords
   Biological processInflammatory response
   Cellular componentGolgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionHydrolase
Transferase
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processMAPK cascade

Inferred from electronic annotation. Source: Ensembl

carbohydrate metabolic process

Traceable author statement. Source: Reactome

embryonic neurocranium morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic viscerocranium morphogenesis

Inferred from electronic annotation. Source: Ensembl

fibroblast growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

forebrain development

Inferred from electronic annotation. Source: Ensembl

glycosaminoglycan biosynthetic process

Traceable author statement. Source: Reactome

glycosaminoglycan metabolic process

Traceable author statement. Source: Reactome

heparan sulfate proteoglycan biosynthetic process

Traceable author statement PubMed 9915799. Source: ProtInc

heparin biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

midbrain development

Inferred from electronic annotation. Source: Ensembl

polysaccharide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

respiratory gaseous exchange

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

smoothened signaling pathway

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_function[heparan sulfate]-glucosamine N-sulfotransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

deacetylase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P52848-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P52848-2)

The sequence of this isoform differs from the canonical sequence as follows:
     523-556: ISIFMTHLSNYGNDRLGLYTFKHLVRFLHSWTNL → VSAPQPMAAGEKGLLHSLSAADTGFLEPGKGGEA
     557-882: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 882882Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1
PRO_0000085210

Regions

Topological domain1 – 1717Cytoplasmic Potential
Transmembrane18 – 3922Helical; Signal-anchor for type II membrane protein; Potential
Topological domain40 – 882843Lumenal Potential
Nucleotide binding614 – 6185PAPS
Nucleotide binding833 – 8375PAPS
Region40 – 598559Heparan sulfate N-deacetylase 1
Region599 – 882284Heparan sulfate N-sulfotransferase 1

Sites

Active site6141For sulfotransferase activity
Binding site7121PAPS

Amino acid modifications

Glycosylation2311N-linked (GlcNAc...) Potential
Glycosylation3511N-linked (GlcNAc...) Potential
Glycosylation4011N-linked (GlcNAc...) Potential
Glycosylation6671N-linked (GlcNAc...) Potential
Disulfide bond818 ↔ 828 Ref.8

Natural variations

Alternative sequence523 – 55634ISIFM…SWTNL → VSAPQPMAAGEKGLLHSLSA ADTGFLEPGKGGEA in isoform 2.
VSP_017397
Alternative sequence557 – 882326Missing in isoform 2.
VSP_017398

Experimental info

Mutagenesis6141K → A: Loss of sulfotransferase activity. Ref.5
Sequence conflict24 – 285FIFCL → QVVCQ in AAH12888. Ref.4
Sequence conflict601P → A in AAA67765. Ref.3
Sequence conflict3641H → Q in AAH12888. Ref.4
Sequence conflict6891R → G in AAA67765. Ref.3
Sequence conflict7431K → R in AAA67765. Ref.3

Secondary structure

................................................ 882
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: D4B716B84A0BF4C4

FASTA882100,868
        10         20         30         40         50         60 
MPALACLRRL CRHVSPQAVL FLLFIFCLFS VFISAYYLYG WKRGLEPSAD APEPDCGDPP 

        70         80         90        100        110        120 
PVAPSRLLPL KPVQAATPSR 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 TQNELRAHIP NFTFNLGYSG 

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

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

       490        500        510        520        530        540 
LPRQTCGLFT HTIFYNEYPG GSSELDKIIN GGELFLTVLL NPISIFMTHL 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 HEVITAGSDA SSKLRALQNR CLVPGWYATH IERWLSAYHA NQILVLDGKL 

       790        800        810        820        830        840 
LRTEPAKVMD MVQKFLGVTN TIDYHKTLAF DPKKGFWCQL LEGGKTKCLG KSKGRKYPEM 

       850        860        870        880 
DLDSRAFLKD YYRDHNIELS KLLYKMGQTL PTWLREDLQN TR 

« Hide

Isoform 2 [UniParc].

Checksum: C3D09802532B4D97
Show »

FASTA55662,065

References

« Hide 'large scale' references
[1]"Cloning of the human heparan sulfate-N-deacetylase/N-sulfotransferase gene from the Treacher Collins syndrome candidate region at 5q32-q33.1."
Dixon J., Loftus S.K., Gladwin A.J., Scambler P.J., Wasmuth J.J., Dixon M.J.
Genomics 26:239-244(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Placenta.
[2]"Localization of human heparan glucosaminyl N-deacetylase/N-sulphotransferase to the trans-Golgi network."
Humphries D.E., Sullivan B.M., Aleixo M.D., Stow J.L.
Biochem. J. 325:351-357(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION.
Tissue: Umbilical vein endothelial cell.
[3]Labell T.L., Milewicz D.J., Bonadio J., Edelhoff S., Disteche C.M., Byers P.H.
Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fibroblast.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Lung.
[5]"A role of Lys614 in the sulfotransferase activity of human heparan sulfate N-deacetylase/N-sulfotransferase."
Sueyoshi T., Kakuta Y., Pedersen L.C., Wall F.E., Pedersen L.G., Negishi M.
FEBS Lett. 433:211-214(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LYS-614.
[6]"Overexpression of different isoforms of glucosaminyl N-deacetylase/N-sulfotransferase results in distinct heparan sulfate N-sulfation patterns."
Pikas D.S., Eriksson I., Kjellen L.
Biochemistry 39:4552-4558(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Antibody-based assay for N-deacetylase activity of heparan sulfate/heparin N-deacetylase/N-sulfotransferase (NDST): novel characteristics of NDST-1 and -2."
van den Born J., Pikas D.S., Pisa B.J., Eriksson I., Kjellen L., Berden J.H.M.
Glycobiology 13:1-10(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[8]"Crystal structure of the sulfotransferase domain of human heparan sulfate N-deacetylase/N-sulfotransferase 1."
Kakuta Y., Sueyoshi T., Negishi M., Pedersen L.C.
J. Biol. Chem. 274:10673-10676(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 579-882 IN COMPLEX WITH PAP, DISULFIDE BOND.
+Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U18918 mRNA. Translation: AAA75281.1.
U36600 mRNA. Translation: AAC27354.1.
U17970 mRNA. Translation: AAA67765.1.
BC012888 mRNA. Translation: AAH12888.1.
CCDSCCDS34277.1. [P52848-1]
PIRA57169.
RefSeqNP_001534.1. NM_001543.4. [P52848-1]
XP_006714846.1. XM_006714783.1. [P52848-1]
UniGeneHs.222055.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1NSTX-ray2.30A558-882[»]
ProteinModelPortalP52848.
SMRP52848. Positions 579-879.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109572. 1 interaction.
STRING9606.ENSP00000261797.

PTM databases

PhosphoSiteP52848.

Proteomic databases

MaxQBP52848.
PaxDbP52848.
PRIDEP52848.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261797; ENSP00000261797; ENSG00000070614. [P52848-1]
GeneID3340.
KEGGhsa:3340.
UCSCuc003lsk.4. human. [P52848-1]
uc003lsl.3. human. [P52848-2]

Organism-specific databases

CTD3340.
GeneCardsGC05P149881.
HGNCHGNC:7680. NDST1.
MIM600853. gene.
neXtProtNX_P52848.
PharmGKBPA31486.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG267831.
HOGENOMHOG000008010.
HOVERGENHBG082011.
InParanoidP52848.
KOK02576.
OMATNTIDYH.
PhylomeDBP52848.
TreeFamTF313193.

Enzyme and pathway databases

BioCycMetaCyc:HS01001-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
SABIO-RKP52848.
UniPathwayUPA00756.
UPA00862.

Gene expression databases

ArrayExpressP52848.
BgeeP52848.
CleanExHS_NDST1.
GenevestigatorP52848.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR021930. Heparan_SO4_deacetylase.
IPR027417. P-loop_NTPase.
IPR000863. Sulfotransferase_dom.
[Graphical view]
PfamPF12062. HSNSD. 1 hit.
PF00685. Sulfotransfer_1. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
ProtoNetSearch...

Other

ChiTaRSNDST1. human.
EvolutionaryTraceP52848.
GeneWikiNDST1.
GenomeRNAi3340.
NextBio13220.
PROP52848.
SOURCESearch...

Entry information

Entry nameNDST1_HUMAN
AccessionPrimary (citable) accession number: P52848
Secondary accession number(s): Q96E57
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM