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Protein

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2

Gene

NDST2

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

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)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei613 – 6131For sulfotransferase activityBy similarity
    Binding sitei711 – 7111PAPSBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi613 – 6175PAPSBy similarity
    Nucleotide bindingi832 – 8365PAPSBy similarity

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, 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

    HGNCiHGNC:7681. NDST2.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1818CytoplasmicSequence analysisAdd
    BLAST
    Transmembranei19 – 3921Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
    BLAST
    Topological domaini40 – 883844LumenalSequence analysisAdd
    BLAST

    GO - Cellular componenti

    • Golgi membrane Source: Reactome
    • integral component of membrane Source: ProtInc
    Complete GO annotation...

    Keywords - Cellular componenti

    Golgi apparatus, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA31487.

    Polymorphism and mutation databases

    BioMutaiNDST2.
    DMDMi1708323.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 883883Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2PRO_0000085212Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi233 – 2331N-linked (GlcNAc...)Sequence analysis
    Glycosylationi350 – 3501N-linked (GlcNAc...)Sequence analysis
    Glycosylationi400 – 4001N-linked (GlcNAc...)Sequence analysis
    Glycosylationi666 – 6661N-linked (GlcNAc...)Sequence analysis
    Glycosylationi726 – 7261N-linked (GlcNAc...)Sequence analysis
    Glycosylationi802 – 8021N-linked (GlcNAc...)Sequence analysis
    Disulfide bondi817 ↔ 827By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    EPDiP52849.
    MaxQBiP52849.
    PaxDbiP52849.
    PeptideAtlasiP52849.
    PRIDEiP52849.

    PTM databases

    iPTMnetiP52849.
    PhosphoSiteiP52849.

    Expressioni

    Gene expression databases

    BgeeiP52849.
    CleanExiHS_NDST2.
    ExpressionAtlasiP52849. baseline and differential.
    GenevisibleiP52849. HS.

    Organism-specific databases

    HPAiHPA051515.

    Interactioni

    Subunit structurei

    Monomer.By similarity

    Protein-protein interaction databases

    BioGridi114081. 15 interactions.
    STRINGi9606.ENSP00000310657.

    Structurei

    3D structure databases

    ProteinModelPortaliP52849.
    SMRiP52849. Positions 579-878.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni41 – 597557Heparan sulfate N-deacetylase 2Add
    BLAST
    Regioni598 – 883286Heparan sulfate N-sulfotransferase 2Add
    BLAST

    Sequence similaritiesi

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3703. Eukaryota.
    ENOG410XQN4. LUCA.
    GeneTreeiENSGT00760000119023.
    HOGENOMiHOG000008010.
    HOVERGENiHBG082011.
    InParanoidiP52849.
    KOiK02577.
    OMAiDKYLNMD.
    OrthoDBiEOG7FXZXJ.
    PhylomeDBiP52849.
    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. 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)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei366 – 37712TEEED…DDMLL → ELIPLLLWHIIV in isoform 2. 1 PublicationVSP_017403Add
    BLAST
    Alternative sequencei378 – 883506Missing in isoform 2. 1 PublicationVSP_017404Add
    BLAST

    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_003626.1. NM_003635.3. [P52849-1]
    XP_011538612.1. XM_011540310.1. [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

    Cross-referencesi

    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_003626.1. NM_003635.3. [P52849-1]
    XP_011538612.1. XM_011540310.1. [P52849-1]
    UniGeneiHs.654758.

    3D structure databases

    ProteinModelPortaliP52849.
    SMRiP52849. Positions 579-878.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114081. 15 interactions.
    STRINGi9606.ENSP00000310657.

    PTM databases

    iPTMnetiP52849.
    PhosphoSiteiP52849.

    Polymorphism and mutation databases

    BioMutaiNDST2.
    DMDMi1708323.

    Proteomic databases

    EPDiP52849.
    MaxQBiP52849.
    PaxDbiP52849.
    PeptideAtlasiP52849.
    PRIDEiP52849.

    Protocols and materials databases

    DNASUi8509.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi8509.
    GeneCardsiNDST2.
    HGNCiHGNC:7681. NDST2.
    HPAiHPA051515.
    MIMi603268. gene.
    neXtProtiNX_P52849.
    PharmGKBiPA31487.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3703. Eukaryota.
    ENOG410XQN4. LUCA.
    GeneTreeiENSGT00760000119023.
    HOGENOMiHOG000008010.
    HOVERGENiHBG082011.
    InParanoidiP52849.
    KOiK02577.
    OMAiDKYLNMD.
    OrthoDBiEOG7FXZXJ.
    PhylomeDBiP52849.
    TreeFamiTF313193.

    Enzyme and pathway databases

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

    Miscellaneous databases

    ChiTaRSiNDST2. human.
    GeneWikiiNDST2.
    GenomeRNAii8509.
    PROiP52849.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP52849.
    CleanExiHS_NDST2.
    ExpressionAtlasiP52849. baseline and differential.
    GenevisibleiP52849. HS.

    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.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "cDNA cloning, genomic organization and chromosomal localization of human heparan glucosaminyl N-deacetylase/N-sulphotransferase-2."
      Humphries D.E., Lanciotti J., Karlinsky J.B.
      Biochem. J. 332:303-307(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
    2. "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 1).
      Tissue: Ovary.
    3. Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
      Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-377 (ISOFORM 2).
      Tissue: Brain.
    4. "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.
    5. "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.
    6. "Characterization of the N-deacetylase domain from the heparan sulfate N-deacetylase/N-sulfotransferase 2."
      Duncan M.B., Liu M., Fox C., Liu J.
      Biochem. Biophys. Res. Commun. 339:1232-1237(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. Cited for: FUNCTION.

    Entry informationi

    Entry nameiNDST2_HUMAN
    AccessioniPrimary (citable) accession number: P52849
    Secondary accession number(s): Q2TB32, Q59H89
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: July 6, 2016
    This is version 140 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

    Complete proteome, Multifunctional enzyme, 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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.