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   11-NOV-2015, entry version 134.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX   PubMed=9601056;
RA   Humphries D.E., Lanciotti J., Karlinsky J.B.;
RT   "cDNA cloning, genomic organization and chromosomal localization of
RT   human 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
RT   project: 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
RT   sulfate/heparin N-deacetylase/N-sulfotransferase (NDST): novel
RT   characteristics of NDST-1 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
RT   N-deacetylase/N-sulfotransferase 2.";
RL   Biochem. Biophys. Res. Commun. 339:1232-1237(2006).
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
CC       heparosan, a prerequisite substrate for later modifications in
CC       heparin biosynthesis. Plays a role in determining the extent and
CC       pattern of sulfation of heparan sulfate.
CC       {ECO:0000269|PubMed:10758005, ECO:0000269|PubMed:12634318,
CC       ECO:0000269|PubMed:16343444}.
CC   -!- CATALYTIC ACTIVITY: 3'-phosphoadenylyl sulfate + [heparan
CC       sulfate]-glucosamine = adenosine 3',5'-bisphosphate + [heparan
CC       sulfate]-N-sulfoglucosamine.
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};
CC       Single-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         Note=No experimental confirmation available.;
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
CC       heparan sulfate modification/sulfation reactions, whereas other
CC       later on fill in or extend already modified heparan sulfate
CC       sequences.
CC   -!- SIMILARITY: Belongs to the sulfotransferase 1 family. NDST
CC       subfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=GGDB; Note=GlycoGene database;
CC       URL="http://jcggdb.jp/rcmg/ggdb/Homolog?cat=symbol&symbol=NDST2";
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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_003626.1; NM_003635.3. [P52849-1]
DR   RefSeq; XP_011538612.1; XM_011540310.1. [P52849-1]
DR   UniGene; Hs.654758; -.
DR   ProteinModelPortal; P52849; -.
DR   SMR; P52849; 579-878.
DR   BioGrid; 114081; 15.
DR   STRING; 9606.ENSP00000310657; -.
DR   PhosphoSite; P52849; -.
DR   BioMuta; NDST2; -.
DR   DMDM; 1708323; -.
DR   MaxQB; P52849; -.
DR   PaxDb; P52849; -.
DR   PRIDE; P52849; -.
DR   DNASU; 8509; -.
DR   Ensembl; ENST00000299641; ENSP00000299641; ENSG00000166507. [P52849-1]
DR   Ensembl; ENST00000309979; ENSP00000310657; ENSG00000166507. [P52849-1]
DR   GeneID; 8509; -.
DR   KEGG; hsa:8509; -.
DR   UCSC; uc001jvk.2; human. [P52849-1]
DR   CTD; 8509; -.
DR   GeneCards; NDST2; -.
DR   HGNC; HGNC:7681; NDST2.
DR   HPA; HPA051515; -.
DR   MIM; 603268; gene.
DR   neXtProt; NX_P52849; -.
DR   PharmGKB; PA31487; -.
DR   eggNOG; KOG3703; Eukaryota.
DR   eggNOG; ENOG410XQN4; LUCA.
DR   GeneTree; ENSGT00760000119023; -.
DR   HOGENOM; HOG000008010; -.
DR   HOVERGEN; HBG082011; -.
DR   InParanoid; P52849; -.
DR   KO; K02577; -.
DR   OMA; DKYLNMD; -.
DR   OrthoDB; EOG7FXZXJ; -.
DR   PhylomeDB; P52849; -.
DR   TreeFam; TF313193; -.
DR   BioCyc; MetaCyc:HS09410-MONOMER; -.
DR   Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR   UniPathway; UPA00756; -.
DR   UniPathway; UPA00862; -.
DR   ChiTaRS; NDST2; human.
DR   GeneWiki; NDST2; -.
DR   GenomeRNAi; 8509; -.
DR   NextBio; 31847; -.
DR   PRO; PR:P52849; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   Bgee; P52849; -.
DR   CleanEx; HS_NDST2; -.
DR   ExpressionAtlas; P52849; baseline and differential.
DR   Genevisible; P52849; HS.
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; IEA:UniProtKB-EC.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   GO; GO:0005975; P:carbohydrate metabolic process; TAS:Reactome.
DR   GO; GO:0006024; P:glycosaminoglycan biosynthetic process; TAS:Reactome.
DR   GO; GO:0030203; P:glycosaminoglycan metabolic process; TAS:Reactome.
DR   GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0030210; P:heparin biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR   Gene3D; 3.40.50.300; -; 1.
DR   InterPro; IPR021930; Heparan_SO4_deacetylase.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR000863; Sulfotransferase_dom.
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; Complete proteome; Disulfide bond; Glycoprotein;
KW   Golgi apparatus; Hydrolase; Membrane; Multifunctional enzyme;
KW   Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN         1    883       Bifunctional heparan sulfate N-
FT                                deacetylase/N-sulfotransferase 2.
FT                                /FTId=PRO_0000085212.
FT   TOPO_DOM      1     18       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM     19     39       Helical; Signal-anchor for type II
FT                                membrane protein. {ECO:0000255}.
FT   TOPO_DOM     40    883       Lumenal. {ECO:0000255}.
FT   NP_BIND     613    617       PAPS. {ECO:0000250}.
FT   NP_BIND     832    836       PAPS. {ECO:0000250}.
FT   REGION       41    597       Heparan sulfate N-deacetylase 2.
FT   REGION      598    883       Heparan sulfate N-sulfotransferase 2.
FT   ACT_SITE    613    613       For sulfotransferase activity.
FT                                {ECO:0000250}.
FT   BINDING     711    711       PAPS. {ECO:0000250}.
FT   CARBOHYD    233    233       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    350    350       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    400    400       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    666    666       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    726    726       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    802    802       N-linked (GlcNAc...). {ECO:0000255}.
FT   DISULFID    817    827       {ECO:0000250}.
FT   VAR_SEQ     366    377       TEEEDAGDDMLL -> ELIPLLLWHIIV (in isoform
FT                                2). {ECO:0000303|Ref.3}.
FT                                /FTId=VSP_017403.
FT   VAR_SEQ     378    883       Missing (in isoform 2).
FT                                {ECO:0000303|Ref.3}.
FT                                /FTId=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
//