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P52848

- NDST1_HUMAN

UniProt

P52848 - NDST1_HUMAN

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Protein
Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1
Gene
NDST1, HSST, HSST1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine = adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine.

Kineticsi

  1. KM=13.3 µM for K5 polysaccharide1 Publication
  2. KM=0.35 µM for N-acetylated HS-II

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei614 – 6141For sulfotransferase activity
Binding sitei712 – 7121PAPS

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi614 – 6185PAPS
Nucleotide bindingi833 – 8375PAPS

GO - Molecular functioni

  1. [heparan sulfate]-glucosamine N-sulfotransferase activity Source: UniProtKB-EC
  2. deacetylase activity Source: Ensembl

GO - Biological processi

  1. MAPK cascade Source: Ensembl
  2. carbohydrate metabolic process Source: Reactome
  3. embryonic neurocranium morphogenesis Source: Ensembl
  4. embryonic viscerocranium morphogenesis Source: Ensembl
  5. fibroblast growth factor receptor signaling pathway Source: Ensembl
  6. forebrain development Source: Ensembl
  7. glycosaminoglycan biosynthetic process Source: Reactome
  8. glycosaminoglycan metabolic process Source: Reactome
  9. heparan sulfate proteoglycan biosynthetic process Source: ProtInc
  10. heparin biosynthetic process Source: UniProtKB-UniPathway
  11. inflammatory response Source: UniProtKB-KW
  12. midbrain development Source: Ensembl
  13. polysaccharide biosynthetic process Source: Ensembl
  14. respiratory gaseous exchange Source: Ensembl
  15. small molecule metabolic process Source: Reactome
  16. smoothened signaling pathway Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Transferase

Keywords - Biological processi

Inflammatory response

Enzyme and pathway databases

BioCyciMetaCyc:HS01001-MONOMER.
ReactomeiREACT_121248. HS-GAG biosynthesis.
SABIO-RKP52848.
UniPathwayiUPA00756.
UPA00862.

Names & Taxonomyi

Protein namesi
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 namesi
Name:NDST1
Synonyms:HSST, HSST1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:7680. NDST1.

Subcellular locationi

Golgi apparatus membrane; Single-pass type II membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1717Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei18 – 3922Helical; Signal-anchor for type II membrane protein; Reviewed prediction
Add
BLAST
Topological domaini40 – 882843Lumenal Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. Golgi membrane Source: Reactome
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi614 – 6141K → A: Loss of sulfotransferase activity. 1 Publication

Organism-specific databases

PharmGKBiPA31486.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 882882Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1
PRO_0000085210Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi231 – 2311N-linked (GlcNAc...) Reviewed prediction
Glycosylationi351 – 3511N-linked (GlcNAc...) Reviewed prediction
Glycosylationi401 – 4011N-linked (GlcNAc...) Reviewed prediction
Glycosylationi667 – 6671N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi818 ↔ 8281 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP52848.
PaxDbiP52848.
PRIDEiP52848.

PTM databases

PhosphoSiteiP52848.

Expressioni

Tissue specificityi

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

Gene expression databases

ArrayExpressiP52848.
BgeeiP52848.
CleanExiHS_NDST1.
GenevestigatoriP52848.

Interactioni

Subunit structurei

Monomer.

Protein-protein interaction databases

BioGridi109572. 1 interaction.
STRINGi9606.ENSP00000261797.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi604 – 6096
Helixi617 – 6259
Beta strandi630 – 6323
Turni637 – 6393
Beta strandi646 – 6483
Helixi649 – 6535
Helixi655 – 6595
Beta strandi672 – 6765
Helixi679 – 6824
Helixi686 – 6938
Beta strandi698 – 7036
Helixi706 – 71914
Helixi723 – 7275
Helixi730 – 7345
Helixi742 – 75211
Helixi753 – 7553
Helixi757 – 7659
Helixi770 – 7723
Beta strandi773 – 7775
Helixi778 – 7836
Helixi785 – 79612
Helixi805 – 8073
Beta strandi808 – 8114
Turni812 – 8154
Beta strandi816 – 8205
Helixi842 – 86625
Helixi872 – 8787

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NSTX-ray2.30A558-882[»]
ProteinModelPortaliP52848.
SMRiP52848. Positions 579-879.

Miscellaneous databases

EvolutionaryTraceiP52848.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni40 – 598559Heparan sulfate N-deacetylase 1
Add
BLAST
Regioni599 – 882284Heparan sulfate N-sulfotransferase 1
Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG267831.
HOGENOMiHOG000008010.
HOVERGENiHBG082011.
InParanoidiP52848.
KOiK02576.
OMAiTNTIDYH.
PhylomeDBiP52848.
TreeFamiTF313193.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR021930. Heparan_SO4_deacetylase.
IPR027417. P-loop_NTPase.
IPR000863. Sulfotransferase_dom.
[Graphical view]
PfamiPF12062. HSNSD. 1 hit.
PF00685. Sulfotransfer_1. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P52848-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MPALACLRRL CRHVSPQAVL FLLFIFCLFS VFISAYYLYG WKRGLEPSAD    50
APEPDCGDPP PVAPSRLLPL KPVQAATPSR TDPLVLVFVE SLYSQLGQEV 100
VAILESSRFK YRTEIAPGKG DMPTLTDKGR GRFALIIYEN ILKYVNLDAW 150
NRELLDKYCV AYGVGIIGFF KANENSLLSA QLKGFPLFLH SNLGLKDCSI 200
NPKSPLLYVT RPSEVEKGVL PGEDWTVFQS NHSTYEPVLL AKTRSSESIP 250
HLGADAGLHA ALHATVVQDL GLHDGIQRVL FGNNLNFWLH KLVFVDAVAF 300
LTGKRLSLPL DRYILVDIDD IFVGKEGTRM KVEDVKALFD TQNELRAHIP 350
NFTFNLGYSG KFFHTGTNAE DAGDDLLLSY VKEFWWFPHM WSHMQPHLFH 400
NQSVLAEQMA LNKKFAVEHG IPTDMGYAVA PHHSGVYPVH VQLYEAWKQV 450
WSIRVTSTEE YPHLKPARYR RGFIHNGIMV LPRQTCGLFT HTIFYNEYPG 500
GSSELDKIIN GGELFLTVLL NPISIFMTHL SNYGNDRLGL YTFKHLVRFL 550
HSWTNLRLQT LPPVQLAQKY FQIFSEEKDP LWQDPCEDKR HKDIWSKEKT 600
CDRFPKLLII GPQKTGTTAL YLFLGMHPDL SSNYPSSETF EEIQFFNGHN 650
YHKGIDWYME FFPIPSNTTS DFYFEKSANY FDSEVAPRRA AALLPKAKVL 700
TILINPADRA YSWYQHQRAH DDPVALKYTF HEVITAGSDA SSKLRALQNR 750
CLVPGWYATH IERWLSAYHA NQILVLDGKL LRTEPAKVMD MVQKFLGVTN 800
TIDYHKTLAF DPKKGFWCQL LEGGKTKCLG KSKGRKYPEM DLDSRAFLKD 850
YYRDHNIELS KLLYKMGQTL PTWLREDLQN TR 882
Length:882
Mass (Da):100,868
Last modified:October 1, 1996 - v1
Checksum:iD4B716B84A0BF4C4
GO
Isoform 2 (identifier: P52848-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     523-556: ISIFMTHLSNYGNDRLGLYTFKHLVRFLHSWTNL → VSAPQPMAAGEKGLLHSLSAADTGFLEPGKGGEA
     557-882: Missing.

Note: No experimental confirmation available.

Show »
Length:556
Mass (Da):62,065
Checksum:iC3D09802532B4D97
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei523 – 55634ISIFM…SWTNL → VSAPQPMAAGEKGLLHSLSA ADTGFLEPGKGGEA in isoform 2.
VSP_017397Add
BLAST
Alternative sequencei557 – 882326Missing in isoform 2.
VSP_017398Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti24 – 285FIFCL → QVVCQ in AAH12888. 1 Publication
Sequence conflicti60 – 601P → A in AAA67765. 1 Publication
Sequence conflicti364 – 3641H → Q in AAH12888. 1 Publication
Sequence conflicti689 – 6891R → G in AAA67765. 1 Publication
Sequence conflicti743 – 7431K → R in AAA67765. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U18918 mRNA. Translation: AAA75281.1.
U36600 mRNA. Translation: AAC27354.1.
U17970 mRNA. Translation: AAA67765.1.
BC012888 mRNA. Translation: AAH12888.1.
CCDSiCCDS34277.1. [P52848-1]
PIRiA57169.
RefSeqiNP_001534.1. NM_001543.4. [P52848-1]
XP_006714846.1. XM_006714783.1. [P52848-1]
UniGeneiHs.222055.

Genome annotation databases

EnsembliENST00000261797; ENSP00000261797; ENSG00000070614. [P52848-1]
GeneIDi3340.
KEGGihsa:3340.
UCSCiuc003lsk.4. human. [P52848-1]
uc003lsl.3. human. [P52848-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

GGDB

GlycoGene database

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U18918 mRNA. Translation: AAA75281.1 .
U36600 mRNA. Translation: AAC27354.1 .
U17970 mRNA. Translation: AAA67765.1 .
BC012888 mRNA. Translation: AAH12888.1 .
CCDSi CCDS34277.1. [P52848-1 ]
PIRi A57169.
RefSeqi NP_001534.1. NM_001543.4. [P52848-1 ]
XP_006714846.1. XM_006714783.1. [P52848-1 ]
UniGenei Hs.222055.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1NST X-ray 2.30 A 558-882 [» ]
ProteinModelPortali P52848.
SMRi P52848. Positions 579-879.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109572. 1 interaction.
STRINGi 9606.ENSP00000261797.

PTM databases

PhosphoSitei P52848.

Proteomic databases

MaxQBi P52848.
PaxDbi P52848.
PRIDEi P52848.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000261797 ; ENSP00000261797 ; ENSG00000070614 . [P52848-1 ]
GeneIDi 3340.
KEGGi hsa:3340.
UCSCi uc003lsk.4. human. [P52848-1 ]
uc003lsl.3. human. [P52848-2 ]

Organism-specific databases

CTDi 3340.
GeneCardsi GC05P149881.
HGNCi HGNC:7680. NDST1.
MIMi 600853. gene.
neXtProti NX_P52848.
PharmGKBi PA31486.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG267831.
HOGENOMi HOG000008010.
HOVERGENi HBG082011.
InParanoidi P52848.
KOi K02576.
OMAi TNTIDYH.
PhylomeDBi P52848.
TreeFami TF313193.

Enzyme and pathway databases

UniPathwayi UPA00756 .
UPA00862 .
BioCyci MetaCyc:HS01001-MONOMER.
Reactomei REACT_121248. HS-GAG biosynthesis.
SABIO-RK P52848.

Miscellaneous databases

ChiTaRSi NDST1. human.
EvolutionaryTracei P52848.
GeneWikii NDST1.
GenomeRNAii 3340.
NextBioi 13220.
PROi P52848.
SOURCEi Search...

Gene expression databases

ArrayExpressi P52848.
Bgeei P52848.
CleanExi HS_NDST1.
Genevestigatori P52848.

Family and domain databases

Gene3Di 3.40.50.300. 1 hit.
InterProi IPR021930. Heparan_SO4_deacetylase.
IPR027417. P-loop_NTPase.
IPR000863. Sulfotransferase_dom.
[Graphical view ]
Pfami PF12062. HSNSD. 1 hit.
PF00685. Sulfotransfer_1. 1 hit.
[Graphical view ]
SUPFAMi SSF52540. SSF52540. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiNDST1_HUMAN
AccessioniPrimary (citable) accession number: P52848
Secondary accession number(s): Q96E57
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 3, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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