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Protein

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2

Gene

NDST2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).4 Publications

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.

Catalytic activityi

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

Kineticsi

  1. KM=4.7 µM for K5 polysaccharide1 Publication
  2. KM=0.76 µM for N-acetylated HS-II1 Publication

    Pathwayi: heparan sulfate biosynthesis

    This protein is involved in the pathway heparan sulfate biosynthesis, which is part of Glycan metabolism.
    View all proteins of this organism that are known to be involved in the pathway heparan sulfate biosynthesis and in Glycan metabolism.

    Pathwayi: heparin biosynthesis

    This protein is involved in the pathway heparin biosynthesis, which is part of Glycan metabolism.
    View all proteins of this organism that are known to be involved in the pathway heparin biosynthesis and in Glycan metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei613For sulfotransferase activityBy similarity1
    Binding sitei711PAPSBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi613 – 617PAPSBy similarity5
    Nucleotide bindingi832 – 836PAPSBy similarity5

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionHydrolase, Multifunctional enzyme, Transferase

    Enzyme and pathway databases

    BioCyciMetaCyc:HS09410-MONOMER
    ReactomeiR-HSA-2022928 HS-GAG biosynthesis
    UniPathwayiUPA00756
    UPA00862

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2 (EC:2.8.2.8)
    Alternative name(s):
    Glucosaminyl N-deacetylase/N-sulfotransferase 2
    Short name:
    NDST-2
    N-heparan sulfate sulfotransferase 2
    Short name:
    N-HSST 2
    Including the following 2 domains:
    Heparan sulfate N-deacetylase 2 (EC:3.-.-.-)
    Heparan sulfate N-sulfotransferase 2 (EC:2.8.2.-)
    Gene namesi
    Name:NDST2
    Synonyms:HSST2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 10

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000166507.16
    HGNCiHGNC:7681 NDST2
    MIMi603268 gene
    neXtProtiNX_P52849

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 18CytoplasmicSequence analysisAdd BLAST18
    Transmembranei19 – 39Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
    Topological domaini40 – 883LumenalSequence analysisAdd BLAST844

    Keywords - Cellular componenti

    Golgi apparatus, Membrane

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi8509
    OpenTargetsiENSG00000166507
    PharmGKBiPA31487

    Polymorphism and mutation databases

    BioMutaiNDST2
    DMDMi1708323

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000852121 – 883Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2Add BLAST883

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi233N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi350N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi400N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi666N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi726N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi802N-linked (GlcNAc...) asparagineSequence analysis1
    Disulfide bondi817 ↔ 827By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    EPDiP52849
    MaxQBiP52849
    PaxDbiP52849
    PeptideAtlasiP52849
    PRIDEiP52849
    ProteomicsDBi56545
    56546 [P52849-2]

    PTM databases

    iPTMnetiP52849
    PhosphoSitePlusiP52849

    Expressioni

    Gene expression databases

    BgeeiENSG00000166507
    CleanExiHS_NDST2
    ExpressionAtlasiP52849 baseline and differential
    GenevisibleiP52849 HS

    Organism-specific databases

    HPAiHPA051515

    Interactioni

    Subunit structurei

    Monomer.By similarity

    Protein-protein interaction databases

    BioGridi114081, 15 interactors
    STRINGi9606.ENSP00000310657

    Structurei

    3D structure databases

    ProteinModelPortaliP52849
    SMRiP52849
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni41 – 597Heparan sulfate N-deacetylase 2Add BLAST557
    Regioni598 – 883Heparan sulfate N-sulfotransferase 2Add BLAST286

    Sequence similaritiesi

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3703 Eukaryota
    ENOG410XQN4 LUCA
    GeneTreeiENSGT00760000119023
    HOGENOMiHOG000008010
    HOVERGENiHBG082011
    InParanoidiP52849
    KOiK02577
    OMAiNYYRGLD
    OrthoDBiEOG091G02CP
    PhylomeDBiP52849
    TreeFamiTF313193

    Family and domain databases

    InterProiView protein in InterPro
    IPR021930 Heparan_SO4_deacetylase
    IPR037359 NST/OST
    IPR027417 P-loop_NTPase
    IPR000863 Sulfotransferase_dom
    PANTHERiPTHR10605 PTHR10605, 1 hit
    PfamiView protein in Pfam
    PF12062 HSNSD, 1 hit
    PF00685 Sulfotransfer_1, 1 hit
    SUPFAMiSSF52540 SSF52540, 1 hit

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P52849-1) [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

            10         20         30         40         50
    MLQLWKVVRP ARQLELHRLI LLLIAFSLGS MGFLAYYVST SPKAKEPLPL
    60 70 80 90 100
    PLGDCSSGGA AGPGPARPPV PPRPPRPPET ARTEPVVLVF VESAYSQLGQ
    110 120 130 140 150
    EIVAILESSR FRYSTELAPG RGDMPTLTDN THGRYVLVIY ENLLKYVNLD
    160 170 180 190 200
    AWSRELLDRY CVEYGVGIIG FFRAHEHSLL SAQLKGFPLF LHSNLGLRDY
    210 220 230 240 250
    QVNPSAPLLH LTRPSRLEPG PLPGDDWTIF QSNHSTYEPV LLASLRPAEP
    260 270 280 290 300
    AVPGPVLRRA RLPTVVQDLG LHDGIQRVLF GHGLSFWLHK LIFVDAVAYL
    310 320 330 340 350
    TGKRLCLDLD RYILVDIDDI FVGKEGTRMK VADVEALLTT QNKLRTLVPN
    360 370 380 390 400
    FTFNLGFSGK FYHTGTEEED AGDDMLLKHR KEFWWFPHMW SHMQPHLFHN
    410 420 430 440 450
    RSVLADQMRL NKQFALEHGI PTDLGYAVAP HHSGVYPIHT QLYEAWKSVW
    460 470 480 490 500
    GIQVTSTEEY PHLRPARYRR GFIHNGIMVL PRQTCGLFTH TIFYNEYPGG
    510 520 530 540 550
    SRELDRSIRG GELFLTVLLN PISIFMTHLS NYGNDRLGLY TFESLVRFLQ
    560 570 580 590 600
    CWTRLRLQTL PPVPLAQKYF ELFPQERSPL WQNPCDDKRH KDIWSKEKTC
    610 620 630 640 650
    DRLPKFLIVG PQKTGTTAIH FFLSLHPAVT SSFPSPSTFE EIQFFNSPNY
    660 670 680 690 700
    HKGIDWYMDF FPVPSNASTD FLFEKSATYF DSEVVPRRGA ALLPRAKIIT
    710 720 730 740 750
    VLTNPADRAY SWYQHQRAHG DPVALNYTFY QVISASSQTP LALRSLQNRC
    760 770 780 790 800
    LVPGYYSTHL QRWLTYYPSG QLLIVDGQEL RTNPAASMES IQKFLGITPF
    810 820 830 840 850
    LNYTRTLRFD DDKGFWCQGL EGGKTRCLGR SKGRRYPDMD TESRLFLTDF
    860 870 880
    FRNHNLELSK LLSRLGQPVP SWLREELQHS SLG
    Length:883
    Mass (Da):100,875
    Last modified:October 1, 1996 - v1
    Checksum:i457166F8FCB403E1
    GO
    Isoform 2 (identifier: P52849-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         366-377: TEEEDAGDDMLL → ELIPLLLWHIIV
         378-883: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:377
    Mass (Da):42,093
    Checksum:iC4831C3D2752087C
    GO

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_017403366 – 377TEEED…DDMLL → ELIPLLLWHIIV in isoform 2. 1 PublicationAdd BLAST12
    Alternative sequenceiVSP_017404378 – 883Missing in isoform 2. 1 PublicationAdd BLAST506

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U36601 mRNA Translation: AAC27120.1
    AF042084 Genomic DNA Translation: AAB97086.1
    BC035711 mRNA Translation: AAH35711.1
    BC110588 mRNA Translation: AAI10589.1
    BC110589 mRNA Translation: AAI10590.1
    AB208870 mRNA Translation: BAD92107.1
    CCDSiCCDS7335.1 [P52849-1]
    RefSeqiNP_001317036.1, NM_001330107.1
    NP_003626.1, NM_003635.3 [P52849-1]
    XP_011538612.1, XM_011540310.2 [P52849-1]
    UniGeneiHs.654758

    Genome annotation databases

    EnsembliENST00000299641; ENSP00000299641; ENSG00000166507 [P52849-1]
    ENST00000309979; ENSP00000310657; ENSG00000166507 [P52849-1]
    GeneIDi8509
    KEGGihsa:8509
    UCSCiuc001jvk.3 human [P52849-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiNDST2_HUMAN
    AccessioniPrimary (citable) accession number: P52849
    Secondary accession number(s): Q2TB32, Q59H89
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: June 20, 2018
    This is version 153 of the entry and version 1 of the sequence. See 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

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: 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. SIMILARITY comments
      Index of protein domains and families

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