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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

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-II1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei614 – 6141For sulfotransferase activity
Binding sitei712 – 7121PAPS1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi614 – 6185PAPS1 Publication
Nucleotide bindingi833 – 8375PAPS1 Publication

GO - Molecular functioni

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

GO - Biological processi

  1. carbohydrate metabolic process Source: Reactome
  2. embryonic neurocranium morphogenesis Source: Ensembl
  3. embryonic viscerocranium morphogenesis Source: Ensembl
  4. fibroblast growth factor receptor signaling pathway Source: Ensembl
  5. forebrain development Source: Ensembl
  6. glycosaminoglycan biosynthetic process Source: Reactome
  7. glycosaminoglycan metabolic process Source: Reactome
  8. heparan sulfate proteoglycan biosynthetic process Source: ProtInc
  9. heparin biosynthetic process Source: UniProtKB-UniPathway
  10. inflammatory response Source: UniProtKB-KW
  11. MAPK cascade Source: Ensembl
  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 1 Publication; Single-pass type II membrane protein 1 Publication

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 1PRO_0000085210Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi231 – 2311N-linked (GlcNAc...)Sequence Analysis
Glycosylationi351 – 3511N-linked (GlcNAc...)Sequence Analysis
Glycosylationi401 – 4011N-linked (GlcNAc...)Sequence Analysis
Glycosylationi667 – 6671N-linked (GlcNAc...)Sequence Analysis
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

BgeeiP52848.
CleanExiHS_NDST1.
ExpressionAtlasiP52848. baseline and differential.
GenevestigatoriP52848.

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

BioGridi109572. 6 interactions.
STRINGi9606.ENSP00000261797.

Structurei

Secondary structure

1
882
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi604 – 6096Combined sources
Helixi617 – 6259Combined sources
Beta strandi630 – 6323Combined sources
Turni637 – 6393Combined sources
Beta strandi646 – 6483Combined sources
Helixi649 – 6535Combined sources
Helixi655 – 6595Combined sources
Beta strandi672 – 6765Combined sources
Helixi679 – 6824Combined sources
Helixi686 – 6938Combined sources
Beta strandi698 – 7036Combined sources
Helixi706 – 71914Combined sources
Helixi723 – 7275Combined sources
Helixi730 – 7345Combined sources
Helixi742 – 75211Combined sources
Helixi753 – 7553Combined sources
Helixi757 – 7659Combined sources
Helixi770 – 7723Combined sources
Beta strandi773 – 7775Combined sources
Helixi778 – 7836Combined sources
Helixi785 – 79612Combined sources
Helixi805 – 8073Combined sources
Beta strandi808 – 8114Combined sources
Turni812 – 8154Combined sources
Beta strandi816 – 8205Combined sources
Helixi842 – 86625Combined sources
Helixi872 – 8787Combined sources

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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP52848.

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1717CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini40 – 882843LumenalSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei18 – 3922Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST

Family & Domainsi

Region

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

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG267831.
GeneTreeiENSGT00760000119023.
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) [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

        10         20         30         40         50
MPALACLRRL CRHVSPQAVL FLLFIFCLFS VFISAYYLYG WKRGLEPSAD
60 70 80 90 100
APEPDCGDPP PVAPSRLLPL KPVQAATPSR TDPLVLVFVE SLYSQLGQEV
110 120 130 140 150
VAILESSRFK YRTEIAPGKG DMPTLTDKGR GRFALIIYEN ILKYVNLDAW
160 170 180 190 200
NRELLDKYCV AYGVGIIGFF KANENSLLSA QLKGFPLFLH SNLGLKDCSI
210 220 230 240 250
NPKSPLLYVT RPSEVEKGVL PGEDWTVFQS NHSTYEPVLL AKTRSSESIP
260 270 280 290 300
HLGADAGLHA ALHATVVQDL GLHDGIQRVL FGNNLNFWLH KLVFVDAVAF
310 320 330 340 350
LTGKRLSLPL DRYILVDIDD IFVGKEGTRM KVEDVKALFD TQNELRAHIP
360 370 380 390 400
NFTFNLGYSG KFFHTGTNAE DAGDDLLLSY VKEFWWFPHM WSHMQPHLFH
410 420 430 440 450
NQSVLAEQMA LNKKFAVEHG IPTDMGYAVA PHHSGVYPVH VQLYEAWKQV
460 470 480 490 500
WSIRVTSTEE YPHLKPARYR RGFIHNGIMV LPRQTCGLFT HTIFYNEYPG
510 520 530 540 550
GSSELDKIIN GGELFLTVLL NPISIFMTHL SNYGNDRLGL YTFKHLVRFL
560 570 580 590 600
HSWTNLRLQT LPPVQLAQKY FQIFSEEKDP LWQDPCEDKR HKDIWSKEKT
610 620 630 640 650
CDRFPKLLII GPQKTGTTAL YLFLGMHPDL SSNYPSSETF EEIQFFNGHN
660 670 680 690 700
YHKGIDWYME FFPIPSNTTS DFYFEKSANY FDSEVAPRRA AALLPKAKVL
710 720 730 740 750
TILINPADRA YSWYQHQRAH DDPVALKYTF HEVITAGSDA SSKLRALQNR
760 770 780 790 800
CLVPGWYATH IERWLSAYHA NQILVLDGKL LRTEPAKVMD MVQKFLGVTN
810 820 830 840 850
TIDYHKTLAF DPKKGFWCQL LEGGKTKCLG KSKGRKYPEM DLDSRAFLKD
860 870 880
YYRDHNIELS KLLYKMGQTL PTWLREDLQN TR
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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti24 – 285FIFCL → QVVCQ in AAH12888. (PubMed:15489334)Curated
Sequence conflicti60 – 601P → A in AAA67765. 1 PublicationCurated
Sequence conflicti364 – 3641H → Q in AAH12888. (PubMed:15489334)Curated
Sequence conflicti689 – 6891R → G in AAA67765. 1 PublicationCurated
Sequence conflicti743 – 7431K → R in AAA67765. 1 PublicationCurated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei523 – 55634ISIFM…SWTNL → VSAPQPMAAGEKGLLHSLSA ADTGFLEPGKGGEA in isoform 2. 1 PublicationVSP_017397Add
BLAST
Alternative sequencei557 – 882326Missing in isoform 2. 1 PublicationVSP_017398Add
BLAST

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. 6 interactions.
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.
GeneTreei ENSGT00760000119023.
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

Bgeei P52848.
CleanExi HS_NDST1.
ExpressionAtlasi P52848. baseline and differential.
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: October 29, 2014
This is version 134 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