ID NDST3_MOUSE Reviewed; 873 AA.
AC Q9EQH7; Q6AXE0; Q9D557;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 27-MAR-2024, entry version 142.
DE RecName: Full=Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 3;
DE EC=2.8.2.8;
DE AltName: Full=Glucosaminyl N-deacetylase/N-sulfotransferase 3;
DE Short=NDST-3;
DE AltName: Full=N-heparan sulfate sulfotransferase 3;
DE Short=N-HSST 3;
DE Includes:
DE RecName: Full=Heparan sulfate N-deacetylase 3;
DE EC=3.-.-.-;
DE Includes:
DE RecName: Full=Heparan sulfate N-sulfotransferase 3;
DE EC=2.8.2.-;
GN Name=Ndst3; Synonyms=Hsst3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=11087757; DOI=10.1074/jbc.m009606200;
RA Aikawa J., Grobe K., Tsujimoto M., Esko J.D.;
RT "Multiple isozymes of heparan sulfate/heparin GlcNAc N-deacetylase/GlcN N-
RT sulfotransferase. Structure and activity of the fourth member, NDST4.";
RL J. Biol. Chem. 276:5876-5882(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Spinal ganglion, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=16056228; DOI=10.1038/ni1233;
RA Wang L., Fuster M., Sriramarao P., Esko J.D.;
RT "Endothelial heparan sulfate deficiency impairs L-selectin- and chemokine-
RT mediated neutrophil trafficking during inflammatory responses.";
RL Nat. Immunol. 6:902-910(2005).
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 Has high deacetylase activity but low sulfotransferase activity.
CC {ECO:0000269|PubMed:11087757}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9EQH7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9EQH7-2; Sequence=VSP_017408, VSP_017409;
CC Name=3;
CC IsoId=Q9EQH7-3; Sequence=VSP_017407;
CC -!- TISSUE SPECIFICITY: Strongly expressed strongly in brain. Expressed at
CC high level at embryonic day 11 compared to other stages of development.
CC Weakly expressed in adult heart, kidney, muscle, endothelial cells and
CC testis but not in other tissues. {ECO:0000269|PubMed:11087757,
CC ECO:0000269|PubMed:16056228}.
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; AF221095; AAG34793.1; -; mRNA.
DR EMBL; AK015768; BAB29967.1; -; mRNA.
DR EMBL; AK141945; BAE24894.1; -; mRNA.
DR EMBL; BC079622; AAH79622.1; -; mRNA.
DR CCDS; CCDS17818.1; -. [Q9EQH7-1]
DR CCDS; CCDS80013.1; -. [Q9EQH7-3]
DR RefSeq; NP_001280611.1; NM_001293682.1.
DR RefSeq; NP_112463.2; NM_031186.3.
DR AlphaFoldDB; Q9EQH7; -.
DR SMR; Q9EQH7; -.
DR BioGRID; 219915; 1.
DR STRING; 10090.ENSMUSP00000118207; -.
DR GlyCosmos; Q9EQH7; 6 sites, No reported glycans.
DR GlyGen; Q9EQH7; 6 sites.
DR iPTMnet; Q9EQH7; -.
DR PhosphoSitePlus; Q9EQH7; -.
DR EPD; Q9EQH7; -.
DR MaxQB; Q9EQH7; -.
DR PaxDb; 10090-ENSMUSP00000118207; -.
DR ProteomicsDB; 253042; -. [Q9EQH7-1]
DR ProteomicsDB; 253043; -. [Q9EQH7-2]
DR ProteomicsDB; 253044; -. [Q9EQH7-3]
DR Antibodypedia; 26593; 146 antibodies from 18 providers.
DR DNASU; 83398; -.
DR Ensembl; ENSMUST00000137404.8; ENSMUSP00000118796.2; ENSMUSG00000027977.16. [Q9EQH7-2]
DR GeneID; 83398; -.
DR KEGG; mmu:83398; -.
DR AGR; MGI:1932544; -.
DR CTD; 9348; -.
DR MGI; MGI:1932544; Ndst3.
DR VEuPathDB; HostDB:ENSMUSG00000027977; -.
DR eggNOG; KOG3703; Eukaryota.
DR GeneTree; ENSGT00940000160665; -.
DR HOGENOM; CLU_011357_1_0_1; -.
DR InParanoid; Q9EQH7; -.
DR OrthoDB; 2913264at2759; -.
DR PhylomeDB; Q9EQH7; -.
DR BRENDA; 2.8.2.8; 3474.
DR Reactome; R-MMU-2022928; HS-GAG biosynthesis.
DR UniPathway; UPA00756; -.
DR UniPathway; UPA00862; -.
DR BioGRID-ORCS; 83398; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Ndst3; mouse.
DR PRO; PR:Q9EQH7; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9EQH7; Protein.
DR Bgee; ENSMUSG00000027977; Expressed in cerebellar cortex and 61 other cell types or tissues.
DR ExpressionAtlas; Q9EQH7; baseline and differential.
DR Genevisible; Q9EQH7; MM.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0015016; F:[heparan sulfate]-glucosamine N-sulfotransferase activity; IDA:MGI.
DR GO; GO:0019213; F:deacetylase activity; IDA:MGI.
DR GO; GO:0102140; F:heparan sulfate N-deacetylase activity; ISO:MGI.
DR GO; GO:0050119; F:N-acetylglucosamine deacetylase activity; IDA:MGI.
DR GO; GO:0008146; F:sulfotransferase activity; IDA:MGI.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IMP:MGI.
DR GO; GO:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; ISO:MGI.
DR GO; GO:0030210; P:heparin biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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:SF29; BIFUNCTIONAL HEPARAN SULFATE N-DEACETYLASE_N-SULFOTRANSFERASE 3; 1.
DR PANTHER; PTHR10605; HEPARAN SULFATE SULFOTRANSFERASE; 1.
DR Pfam; PF12062; HSNSD; 1.
DR Pfam; PF00685; Sulfotransfer_1; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
PE 2: Evidence at transcript 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..873
FT /note="Bifunctional heparan sulfate N-deacetylase/N-
FT sulfotransferase 3"
FT /id="PRO_0000225660"
FT TOPO_DOM 1..13
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 14..34
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 35..873
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 36..589
FT /note="Heparan sulfate N-deacetylase 3"
FT REGION 590..873
FT /note="Heparan sulfate N-sulfotransferase 3"
FT ACT_SITE 605
FT /note="For sulfotransferase activity"
FT /evidence="ECO:0000250"
FT BINDING 605..609
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 703
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 824..828
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT CARBOHYD 146
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 226
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 392
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 658
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 794
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 809..819
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..415
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_017407"
FT VAR_SEQ 635..642
FT /note="QFFNRNNY -> HGFLPSPI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_017408"
FT VAR_SEQ 643..873
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_017409"
FT CONFLICT 97
FT /note="M -> T (in Ref. 1; AAG34793)"
FT /evidence="ECO:0000305"
FT CONFLICT 177
FT /note="F -> V (in Ref. 1; AAG34793)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="D -> E (in Ref. 1; AAG34793)"
FT /evidence="ECO:0000305"
FT CONFLICT 726
FT /note="S -> F (in Ref. 2; BAB29967)"
FT /evidence="ECO:0000305"
FT CONFLICT 771
FT /note="H -> Q (in Ref. 2; BAB29967)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 873 AA; 101040 MW; 3B54622D85F75EF9 CRC64;
MSFIMKPHRH FQRTLILLAT FCMVSIIISA YYLYSGYKQE SEVSGRASEV DCGDLQHIPS
RLMEVRRTMI SDASRTDPTV LVFVESQYSS LGQDIIMMLE SIRFHYHTEI APGKGDLPAL
TDNVKGKYVL IIYENILKYI NMDSWNRSLL DKYCIEYGVG IIGFHKTSEK NLQSFQFRGF
PFSISGNLAV KDCCINPHSP LLRVTKSSKL DRGSLPGTDW TVFQINHSTY QPVIFAKVKT
PENLSPPISK HAFYATIIHD LGLHDGIQRV LFGNNLNFWL HKLIFIDAIS FLSGKRLTLS
LDRYILVDID DIFVGKEGTR MNTNDVKALL DTQNLLRTQI TNFTFNLGFS GKFYHTGTEE
EDEGDDCLLG SVDEFWWFPH MWSHMQPHLF HNESSLIEQM ILNKKFALEH GIPTDMGYAV
SPHHSGVYPV HVQLYEAWKK VWNIKITSTE EYPHLKPARY RRGFIHKNIM VLPRQTCGLF
THTIFYKEYP GGPRELDKSI HGGELFFTVV LNPISIFMTH LSNYGNDRLG LYTFVNLANF
VQTWTNLRLQ TLPPAQLAHK YFELFPDQKD PLWQNPCDDK RHRDIWSKEK TCDRLPKFLV
IGPQKTGTTA LCLFLIMHPS ILSNSPSPKS FEEVQFFNRN NYHRGIDWYM DFFPVPSNVT
TDFLFEKSAN YFHSEDAPKR AASLVPKAKI ITILIDPSDR AYSWYQHQRS HEDPAALKFS
FYEVISAGPN APWELRTLQK RCLVPGWYAN HIERWLVYFP PFQLLIIDGQ HLRTTPATVM
DEVQKFLGVS PHYNYSEALT FDSHKGFWCQ LLEEGKTKCL GKSKGRKYPP MDSDSRAFLS
SYYRDHNVEL SKLLHRLGQP LPSWLRQELQ KVR
//
