NDST2_HUMAN
ID NDST2_HUMAN Reviewed; 883 AA.
AC P52849; Q2TB32; Q59H89;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2;
DE EC=2.8.2.8;
DE AltName: Full=Glucosaminyl N-deacetylase/N-sulfotransferase 2;
DE Short=NDST-2;
DE AltName: Full=N-heparan sulfate sulfotransferase 2;
DE Short=N-HSST 2;
DE Includes:
DE RecName: Full=Heparan sulfate N-deacetylase 2;
DE EC=3.-.-.-;
DE Includes:
DE RecName: Full=Heparan sulfate N-sulfotransferase 2;
DE EC=2.8.2.-;
GN Name=NDST2; Synonyms=HSST2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=9601056; DOI=10.1042/bj3320303;
RA Humphries D.E., Lanciotti J., Karlinsky J.B.;
RT "cDNA cloning, genomic organization and chromosomal localization of human
RT heparan glucosaminyl N-deacetylase/N-sulphotransferase-2.";
RL Biochem. J. 332:303-307(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-377 (ISOFORM 2).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION.
RX PubMed=10758005; DOI=10.1021/bi992524l;
RA Pikas D.S., Eriksson I., Kjellen L.;
RT "Overexpression of different isoforms of glucosaminyl N-deacetylase/N-
RT sulfotransferase results in distinct heparan sulfate N-sulfation
RT patterns.";
RL Biochemistry 39:4552-4558(2000).
RN [5]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12634318; DOI=10.1093/glycob/cwg011;
RA van den Born J., Pikas D.S., Pisa B.J., Eriksson I., Kjellen L.,
RA Berden J.H.M.;
RT "Antibody-based assay for N-deacetylase activity of heparan sulfate/heparin
RT N-deacetylase/N-sulfotransferase (NDST): novel characteristics of NDST-1
RT and -2.";
RL Glycobiology 13:1-10(2003).
RN [6]
RP FUNCTION.
RX PubMed=16343444; DOI=10.1016/j.bbrc.2005.11.142;
RA Duncan M.B., Liu M., Fox C., Liu J.;
RT "Characterization of the N-deacetylase domain from the heparan sulfate N-
RT deacetylase/N-sulfotransferase 2.";
RL Biochem. Biophys. Res. Commun. 339:1232-1237(2006).
RN [7]
RP FUNCTION.
RX PubMed=22660413; DOI=10.1038/ncb2502;
RA Baietti M.F., Zhang Z., Mortier E., Melchior A., Degeest G., Geeraerts A.,
RA Ivarsson Y., Depoortere F., Coomans C., Vermeiren E., Zimmermann P.,
RA David G.;
RT "Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.";
RL Nat. Cell Biol. 14:677-685(2012).
CC -!- FUNCTION: Essential bifunctional enzyme that catalyzes both the N-
CC deacetylation and the N-sulfation of glucosamine (GlcNAc) of the
CC glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA
CC disaccharide repeating sugar backbone to make N-sulfated heparosan, a
CC prerequisite substrate for later modifications in heparin biosynthesis.
CC Plays a role in determining the extent and pattern of sulfation of
CC heparan sulfate. Required for the exosomal release of SDCBP, CD63 and
CC syndecan (PubMed:22660413). {ECO:0000269|PubMed:10758005,
CC ECO:0000269|PubMed:12634318, ECO:0000269|PubMed:16343444,
CC ECO:0000269|PubMed:22660413}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3'-phosphoadenylyl sulfate + alpha-D-glucosaminyl-[heparan
CC sulfate](n) = adenosine 3',5'-bisphosphate + 2 H(+) + N-sulfo-alpha-
CC D-glucosaminyl-[heparan sulfate](n); Xref=Rhea:RHEA:21980, Rhea:RHEA-
CC COMP:9830, Rhea:RHEA-COMP:14602, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58339, ChEBI:CHEBI:58343, ChEBI:CHEBI:58388,
CC ChEBI:CHEBI:140572; EC=2.8.2.8;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.7 uM for K5 polysaccharide {ECO:0000269|PubMed:12634318};
CC KM=0.76 uM for N-acetylated HS-II {ECO:0000269|PubMed:12634318};
CC -!- PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
CC -!- PATHWAY: Glycan metabolism; heparin biosynthesis.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P52849-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P52849-2; Sequence=VSP_017403, VSP_017404;
CC -!- MISCELLANEOUS: The presence of 4 different heparan sulfate N-
CC deacetylase/N-sulfotransferase enzymes in mammals, as well as
CC differences in their enzyme activity suggest that some initiate heparan
CC sulfate modification/sulfation reactions, whereas other later on fill
CC in or extend already modified heparan sulfate sequences.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. NDST subfamily.
CC {ECO:0000305}.
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DR EMBL; U36601; AAC27120.1; -; mRNA.
DR EMBL; AF042084; AAB97086.1; -; Genomic_DNA.
DR EMBL; BC035711; AAH35711.1; -; mRNA.
DR EMBL; BC110588; AAI10589.1; -; mRNA.
DR EMBL; BC110589; AAI10590.1; -; mRNA.
DR EMBL; AB208870; BAD92107.1; -; mRNA.
DR CCDS; CCDS7335.1; -. [P52849-1]
DR RefSeq; NP_001317036.1; NM_001330107.1.
DR RefSeq; NP_003626.1; NM_003635.3. [P52849-1]
DR RefSeq; XP_011538612.1; XM_011540310.2. [P52849-1]
DR AlphaFoldDB; P52849; -.
DR SMR; P52849; -.
DR BioGRID; 114081; 45.
DR IntAct; P52849; 11.
DR STRING; 9606.ENSP00000310657; -.
DR GlyGen; P52849; 6 sites.
DR iPTMnet; P52849; -.
DR PhosphoSitePlus; P52849; -.
DR BioMuta; NDST2; -.
DR DMDM; 1708323; -.
DR EPD; P52849; -.
DR jPOST; P52849; -.
DR MassIVE; P52849; -.
DR MaxQB; P52849; -.
DR PaxDb; P52849; -.
DR PeptideAtlas; P52849; -.
DR PRIDE; P52849; -.
DR ProteomicsDB; 56545; -. [P52849-1]
DR ProteomicsDB; 56546; -. [P52849-2]
DR Antibodypedia; 55170; 85 antibodies from 19 providers.
DR DNASU; 8509; -.
DR Ensembl; ENST00000299641.8; ENSP00000299641.5; ENSG00000166507.19. [P52849-1]
DR Ensembl; ENST00000309979.11; ENSP00000310657.6; ENSG00000166507.19. [P52849-1]
DR GeneID; 8509; -.
DR KEGG; hsa:8509; -.
DR MANE-Select; ENST00000309979.11; ENSP00000310657.6; NM_003635.4; NP_003626.1.
DR UCSC; uc001jvk.3; human. [P52849-1]
DR CTD; 8509; -.
DR DisGeNET; 8509; -.
DR GeneCards; NDST2; -.
DR HGNC; HGNC:7681; NDST2.
DR HPA; ENSG00000166507; Low tissue specificity.
DR MIM; 603268; gene.
DR neXtProt; NX_P52849; -.
DR OpenTargets; ENSG00000166507; -.
DR PharmGKB; PA31487; -.
DR VEuPathDB; HostDB:ENSG00000166507; -.
DR eggNOG; KOG3703; Eukaryota.
DR GeneTree; ENSGT00940000156237; -.
DR HOGENOM; CLU_011357_2_0_1; -.
DR InParanoid; P52849; -.
DR OMA; KHIWRVK; -.
DR PhylomeDB; P52849; -.
DR TreeFam; TF313193; -.
DR BioCyc; MetaCyc:HS09410-MON; -.
DR BRENDA; 2.8.2.8; 2681.
DR PathwayCommons; P52849; -.
DR Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR SignaLink; P52849; -.
DR UniPathway; UPA00756; -.
DR UniPathway; UPA00862; -.
DR BioGRID-ORCS; 8509; 18 hits in 1072 CRISPR screens.
DR ChiTaRS; NDST2; human.
DR GeneWiki; NDST2; -.
DR GenomeRNAi; 8509; -.
DR Pharos; P52849; Tbio.
DR PRO; PR:P52849; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P52849; protein.
DR Bgee; ENSG00000166507; Expressed in spleen and 95 other tissues.
DR ExpressionAtlas; P52849; baseline and differential.
DR Genevisible; P52849; HS.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0015016; F:[heparan sulfate]-glucosamine N-sulfotransferase activity; IBA:GO_Central.
DR GO; GO:0019213; F:deacetylase activity; IBA:GO_Central.
DR GO; GO:0102140; F:heparan sulfate N-deacetylase activity; IEA:Ensembl.
DR GO; GO:0050119; F:N-acetylglucosamine deacetylase activity; TAS:Reactome.
DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; TAS:Reactome.
DR GO; GO:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; IBA:GO_Central.
DR GO; GO:0030210; P:heparin biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0002448; P:mast cell mediated immunity; IEA:Ensembl.
DR GO; GO:0002002; P:regulation of angiotensin levels in blood; IEA:Ensembl.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR021930; Heparan_SO4_deacetylase.
DR InterPro; IPR037359; NST/OST.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000863; Sulfotransferase_dom.
DR PANTHER; PTHR10605; PTHR10605; 1.
DR Pfam; PF12062; HSNSD; 1.
DR Pfam; PF00685; Sulfotransfer_1; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Glycoprotein; Golgi apparatus;
KW Hydrolase; Membrane; Multifunctional enzyme; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..883
FT /note="Bifunctional heparan sulfate N-deacetylase/N-
FT sulfotransferase 2"
FT /id="PRO_0000085212"
FT TOPO_DOM 1..18
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 19..39
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 40..883
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 41..597
FT /note="Heparan sulfate N-deacetylase 2"
FT REGION 49..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 598..883
FT /note="Heparan sulfate N-sulfotransferase 2"
FT COMPBIAS 64..81
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 613
FT /note="For sulfotransferase activity"
FT /evidence="ECO:0000250"
FT BINDING 613..617
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 711
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 832..836
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT CARBOHYD 233
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 400
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 666
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 726
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 802
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 817..827
FT /evidence="ECO:0000250"
FT VAR_SEQ 366..377
FT /note="TEEEDAGDDMLL -> ELIPLLLWHIIV (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_017403"
FT VAR_SEQ 378..883
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_017404"
SQ SEQUENCE 883 AA; 100875 MW; 457166F8FCB403E1 CRC64;
MLQLWKVVRP ARQLELHRLI LLLIAFSLGS MGFLAYYVST SPKAKEPLPL PLGDCSSGGA
AGPGPARPPV PPRPPRPPET ARTEPVVLVF VESAYSQLGQ EIVAILESSR FRYSTELAPG
RGDMPTLTDN THGRYVLVIY ENLLKYVNLD AWSRELLDRY CVEYGVGIIG FFRAHEHSLL
SAQLKGFPLF LHSNLGLRDY QVNPSAPLLH LTRPSRLEPG PLPGDDWTIF QSNHSTYEPV
LLASLRPAEP AVPGPVLRRA RLPTVVQDLG LHDGIQRVLF GHGLSFWLHK LIFVDAVAYL
TGKRLCLDLD RYILVDIDDI FVGKEGTRMK VADVEALLTT QNKLRTLVPN FTFNLGFSGK
FYHTGTEEED AGDDMLLKHR KEFWWFPHMW SHMQPHLFHN RSVLADQMRL NKQFALEHGI
PTDLGYAVAP HHSGVYPIHT QLYEAWKSVW GIQVTSTEEY PHLRPARYRR GFIHNGIMVL
PRQTCGLFTH TIFYNEYPGG SRELDRSIRG GELFLTVLLN PISIFMTHLS NYGNDRLGLY
TFESLVRFLQ CWTRLRLQTL PPVPLAQKYF ELFPQERSPL WQNPCDDKRH KDIWSKEKTC
DRLPKFLIVG PQKTGTTAIH FFLSLHPAVT SSFPSPSTFE EIQFFNSPNY HKGIDWYMDF
FPVPSNASTD FLFEKSATYF DSEVVPRRGA ALLPRAKIIT VLTNPADRAY SWYQHQRAHG
DPVALNYTFY QVISASSQTP LALRSLQNRC LVPGYYSTHL QRWLTYYPSG QLLIVDGQEL
RTNPAASMES IQKFLGITPF LNYTRTLRFD DDKGFWCQGL EGGKTRCLGR SKGRRYPDMD
TESRLFLTDF FRNHNLELSK LLSRLGQPVP SWLREELQHS SLG
