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P52848

- NDST1_HUMAN

UniProt

P52848 - NDST1_HUMAN

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
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    • History
      Entry version 133 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    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

    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

    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

    ArrayExpressiP52848.
    BgeeiP52848.
    CleanExiHS_NDST1.
    GenevestigatoriP52848.

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    BioGridi109572. 1 interaction.
    STRINGi9606.ENSP00000261797.

    Structurei

    Secondary structure

    1
    882
    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.
    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.
    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

    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. 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

    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 1, 2014
    This is version 133 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