NDST_DROME
ID NDST_DROME Reviewed; 1048 AA.
AC Q9V3L1;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase;
DE EC=2.8.2.8;
DE AltName: Full=Glucosaminyl N-deacetylase/N-sulfotransferase;
DE AltName: Full=Sulfateless;
DE Includes:
DE RecName: Full=Heparan sulfate N-deacetylase;
DE EC=3.-.-.-;
DE Includes:
DE RecName: Full=Heparan sulfate N-sulfotransferase;
DE EC=2.8.2.-;
GN Name=sfl; ORFNames=CG8339;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION IN WG SIGNALING.
RX PubMed=10421372; DOI=10.1038/22343;
RA Lin X., Perrimon N.;
RT "Dally cooperates with Drosophila Frizzled 2 to transduce Wingless
RT signalling.";
RL Nature 400:281-284(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP FUNCTION IN FGF RECEPTOR SIGNALING.
RX PubMed=10433902; DOI=10.1242/dev.126.17.3715;
RA Lin X., Buff E.M., Perrimon N., Michelson A.M.;
RT "Heparan sulfate proteoglycans are essential for FGF receptor signaling
RT during Drosophila embryonic development.";
RL Development 126:3715-3723(1999).
RN [5]
RP FUNCTION.
RX PubMed=10644674; DOI=10.1074/jbc.275.4.2269;
RA Toyoda H., Kinoshita-Toyoda A., Selleck S.B.;
RT "Structural analysis of glycosaminoglycans in Drosophila and Caenorhabditis
RT elegans and demonstration that tout-velu, a Drosophila gene related to EXT
RT tumor suppressors, affects heparan sulfate in vivo.";
RL J. Biol. Chem. 275:2269-2275(2000).
RN [6]
RP FUNCTION.
RX PubMed=15531366; DOI=10.1016/j.ydbio.2004.08.023;
RA Baeg G.-H., Selva E.M., Goodman R.M., Dasgupta R., Perrimon N.;
RT "The Wingless morphogen gradient is established by the cooperative action
RT of Frizzled and Heparan Sulfate Proteoglycan receptors.";
RL Dev. Biol. 276:89-100(2004).
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 diffusion of morphogen wingless (wg) via its role in
CC heparan sulfate proteoglycans (HSPGs) biosynthesis, HSPGs being
CC required for movement of wg morphogens. Required for wg signaling
CC during both embryonic and imaginal disk development. Also required for
CC FGF receptor signaling. {ECO:0000269|PubMed:10421372,
CC ECO:0000269|PubMed:10433902, ECO:0000269|PubMed:10644674,
CC ECO:0000269|PubMed:15531366}.
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 -!- 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 -!- SIMILARITY: Belongs to the sulfotransferase 1 family. NDST subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-154 is the initiator.
CC {ECO:0000305}.
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DR EMBL; AF175689; AAD51842.1; -; mRNA.
DR EMBL; AE014296; AAF50658.1; -; Genomic_DNA.
DR RefSeq; NP_001163354.1; NM_001169883.3.
DR RefSeq; NP_523946.1; NM_079222.5.
DR AlphaFoldDB; Q9V3L1; -.
DR SMR; Q9V3L1; -.
DR BioGRID; 64188; 11.
DR IntAct; Q9V3L1; 6.
DR STRING; 7227.FBpp0076677; -.
DR GlyGen; Q9V3L1; 4 sites.
DR PaxDb; Q9V3L1; -.
DR DNASU; 38736; -.
DR EnsemblMetazoa; FBtr0076968; FBpp0076677; FBgn0020251.
DR EnsemblMetazoa; FBtr0301562; FBpp0290777; FBgn0020251.
DR GeneID; 38736; -.
DR KEGG; dme:Dmel_CG8339; -.
DR UCSC; CG8339-RA; d. melanogaster.
DR CTD; 38736; -.
DR FlyBase; FBgn0020251; sfl.
DR VEuPathDB; VectorBase:FBgn0020251; -.
DR eggNOG; KOG3703; Eukaryota.
DR GeneTree; ENSGT00940000168016; -.
DR HOGENOM; CLU_011357_2_0_1; -.
DR InParanoid; Q9V3L1; -.
DR OMA; EMHLNYA; -.
DR OrthoDB; 388292at2759; -.
DR PhylomeDB; Q9V3L1; -.
DR Reactome; R-DME-2022928; HS-GAG biosynthesis.
DR SignaLink; Q9V3L1; -.
DR UniPathway; UPA00756; -.
DR UniPathway; UPA00862; -.
DR BioGRID-ORCS; 38736; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 38736; -.
DR PRO; PR:Q9V3L1; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0020251; Expressed in brain and 19 other tissues.
DR ExpressionAtlas; Q9V3L1; baseline and differential.
DR Genevisible; Q9V3L1; DM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:FlyBase.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000137; C:Golgi cis cisterna; IDA:FlyBase.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; ISS:FlyBase.
DR GO; GO:0008146; F:sulfotransferase activity; IMP:UniProtKB.
DR GO; GO:0007427; P:epithelial cell migration, open tracheal system; IMP:UniProtKB.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; IMP:UniProtKB.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IMP:FlyBase.
DR GO; GO:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; IMP:UniProtKB.
DR GO; GO:0030210; P:heparin biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008587; P:imaginal disc-derived wing margin morphogenesis; IMP:FlyBase.
DR GO; GO:0007474; P:imaginal disc-derived wing vein specification; IMP:FlyBase.
DR GO; GO:0007509; P:mesoderm migration involved in gastrulation; IMP:UniProtKB.
DR GO; GO:0045570; P:regulation of imaginal disc growth; IMP:FlyBase.
DR GO; GO:0007367; P:segment polarity determination; IMP:FlyBase.
DR GO; GO:0007283; P:spermatogenesis; IMP:FlyBase.
DR GO; GO:0006790; P:sulfur compound metabolic process; IMP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IMP:UniProtKB.
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 Disulfide bond; Glycoprotein; Golgi apparatus; Hydrolase; Membrane;
KW Multifunctional enzyme; Reference proteome; Signal-anchor; Transferase;
KW Transmembrane; Transmembrane helix; Wnt signaling pathway.
FT CHAIN 1..1048
FT /note="Bifunctional heparan sulfate N-deacetylase/N-
FT sulfotransferase"
FT /id="PRO_0000085226"
FT TOPO_DOM 1..172
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..192
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 193..1048
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 192..752
FT /note="Heparan sulfate N-deacetylase"
FT REGION 753..1048
FT /note="Heparan sulfate N-sulfotransferase"
FT ACT_SITE 768
FT /note="For sulfotransferase activity"
FT /evidence="ECO:0000250"
FT BINDING 768..772
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 877
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 998..1002
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT CARBOHYD 388
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 555
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 823
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 892
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 983..993
FT /evidence="ECO:0000250"
SQ SEQUENCE 1048 AA; 118590 MW; A7E56155578D564E CRC64;
MTISGGNQHN NNANRKYEKL IKQPQMQFGS SVTGTQTDVD SCRDADADAN AVRQDFSNFN
KHFGNGHAIT DRTMLLRLED DVTTAAGIVT YKGKSNGNGN GNGNGSIGSI SLDFNGSPTS
STSIGIASGS SSNTHLASGG GVGGIGGSEP AGWMCHCCNL IARRCFGINV RRCVLALLAI
TMVSIFYYTH YVDTGVFNGL IQRDTHPAPI INCRMINSGG KHIRNASPAP DHRSEARLRI
DPKVLVFVET TYSGLGRDIA ELLVYNRIKY KIEVAGKSLP VLTNLDKGRY GVIVFENLDK
YLNMDKWNRE LLDKYCREYS VGIVGFVSPS EETLVGAQLR DFPLFVNTNL RLRDASLNPL
SSVLRLTRAG ETAWGALPGD DWAVFQHNHS TYEPVEWAQR NTQEYPADSV GQVQLPLTTV
LQDRGQLDGI QRVLFGSSLR FWLHRLVFLD ALSYLSHGQL SLNLERMILV DIDDIFVGEK
GTRLRPDDVR ALIATQKNIA AMVPGFRFNL GFSGKYYHHG TREENLGDDF LLQNVQEFNW
FSHMWKHQQP HLYDNLTLLM AEMHLNYAFA VDHNIPTDSG YSISPHHSGV YPAHELLYMA
WKKVWNVKVT STEEYPHLRP ARLRRGFIHR NIMVLPRQTC GLFTHTMYID RYPGGRDKLD
ESIQGGELFQ TIVYNPINIF MTHMSNYGSD RLALYTFQSV IKFLQCWTNL KLASAPPVQL
AEMYFRLHPE EVDPVWGNPC DDVRHKKIWS KTKNCDSLPK FLVIGPQKTG TTALYTFLSM
HGSIASNIAS PETFEEVQFF NGNNYYRGLD WYMDFFPSES LPNTSSPMPT QLGSPRFMFE
KSATYFDGEA VPKRSHALLP HAKIVTILIS PAKRAYSWYQ HQRSHGDVIA NNYSFYQVIT
ASDSAPRALK DLRNRCLNPG KYAQHLEHWL AYYPAQQLHI IDGEQLRLNP IDVMNELQRF
LKIQPLLDYS NHLRYDVKKG FYCQAVSEKR NKCLGKSKGR QYPAMDERSA KLLQRYYLNH
NTALVKLLKK LGSRPIPQWL KDDLSTGT
