NDST1_MOUSE
ID NDST1_MOUSE Reviewed; 882 AA.
AC Q3UHN9; O70353; Q3TBX3; Q3TDS3; Q8BZE5; Q9R206;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1 {ECO:0000305|PubMed:10758005};
DE AltName: Full=Glucosaminyl N-deacetylase/N-sulfotransferase 1;
DE Short=NDST-1 {ECO:0000303|PubMed:10758005};
DE AltName: Full=N-heparan sulfate sulfotransferase 1;
DE Short=N-HSST 1;
DE AltName: Full=[Heparan sulfate]-glucosamine N-sulfotransferase 1;
DE Short=HSNST 1;
DE Includes:
DE RecName: Full=Heparan sulfate N-deacetylase 1;
DE EC=3.5.1.- {ECO:0000269|PubMed:10758005, ECO:0000269|PubMed:12590599, ECO:0000269|PubMed:12634318};
DE Includes:
DE RecName: Full=Heparan sulfate N-sulfotransferase 1;
DE EC=2.8.2.8 {ECO:0000269|PubMed:10758005, ECO:0000269|PubMed:11087757, ECO:0000269|PubMed:12590599, ECO:0000269|PubMed:12634318, ECO:0000269|PubMed:16020517, ECO:0000269|PubMed:16056228, ECO:0000269|PubMed:18337501};
GN Name=Ndst1 {ECO:0000312|MGI:MGI:104719};
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).
RC STRAIN=Leaden X A1; TISSUE=Liver;
RX PubMed=9565617; DOI=10.1074/jbc.273.19.11902;
RA Kusche-Gullberg M., Eriksson I., Pikas D.S., Kjellen L.;
RT "Identification and expression in mouse of two heparan sulfate glucosaminyl
RT N-deacetylase/N-sulfotransferase genes.";
RL J. Biol. Chem. 273:11902-11907(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Lung;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Urinary bladder;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
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 [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10664446; DOI=10.1016/s0014-5793(00)01111-x;
RA Fan G., Xiao L., Cheng L., Wang X., Sun B., Hu G.;
RT "Targeted disruption of NDST-1 gene leads to pulmonary hypoplasia and
RT neonatal respiratory distress in mice.";
RL FEBS Lett. 467:7-11(2000).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=10852901; DOI=10.1074/jbc.c000359200;
RA Ringvall M., Ledin J., Holmborn K., van Kuppevelt T., Ellin F.,
RA Eriksson I., Olofsson A.M., Kjellen L., Forsberg E.;
RT "Defective heparan sulfate biosynthesis and neonatal lethality in mice
RT lacking N-deacetylase/N-sulfotransferase-1.";
RL J. Biol. Chem. 275:25926-25930(2000).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF CYS-486 AND
RP LYS-614.
RX PubMed=12590599; DOI=10.1021/bi026928g;
RA Bengtsson J., Eriksson I., Kjellen L.;
RT "Distinct effects on heparan sulfate structure by different active site
RT mutations in NDST-1.";
RL Biochemistry 42:2110-2115(2003).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP ACTIVITY REGULATION.
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 [10]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=12692154; DOI=10.1242/jcs.00447;
RA Jenniskens G.J., Ringvall M., Koopman W.J., Ledin J., Kjellen L.,
RA Willems P.H.G.M., Forsberg E., Veerkamp J.H., van Kuppevelt T.H.;
RT "Disturbed Ca2+ kinetics in N-deacetylase/N-sulfotransferase-1 defective
RT myotubes.";
RL J. Cell Sci. 116:2187-2193(2003).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16020517; DOI=10.1242/dev.01935;
RA Grobe K., Inatani M., Pallerla S.R., Castagnola J., Yamaguchi Y.,
RA Esko J.D.;
RT "Cerebral hypoplasia and craniofacial defects in mice lacking heparan
RT sulfate Ndst1 gene function.";
RL Development 132:3777-3786(2005).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND DISRUPTION PHENOTYPE.
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).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH EXT2.
RX PubMed=18337501; DOI=10.1073/pnas.0705807105;
RA Presto J., Thuveson M., Carlsson P., Busse M., Wilen M., Eriksson I.,
RA Kusche-Gullberg M., Kjellen L.;
RT "Heparan sulfate biosynthesis enzymes EXT1 and EXT2 affect NDST1 expression
RT and heparan sulfate sulfation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:4751-4756(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (PubMed:11087757, PubMed:10758005,
CC PubMed:10664446, PubMed:12590599, PubMed:12692154, PubMed:16020517,
CC PubMed:16056228, PubMed:18337501). 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 (Probable). Plays a role in determining the extent and pattern of
CC sulfation of heparan sulfate (Probable). Participates in biosynthesis
CC of heparan sulfate that can ultimately serve as L-selectin ligands,
CC thereby playing a role in inflammatory response (PubMed:16056228).
CC Required for the exosomal release of SDCBP, CD63 and syndecan (By
CC similarity). {ECO:0000250|UniProtKB:P52848,
CC ECO:0000269|PubMed:10664446, ECO:0000269|PubMed:10758005,
CC ECO:0000269|PubMed:11087757, ECO:0000269|PubMed:12590599,
CC ECO:0000269|PubMed:12692154, ECO:0000269|PubMed:16020517,
CC ECO:0000269|PubMed:16056228, ECO:0000269|PubMed:18337501,
CC ECO:0000305|PubMed:12634318}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-acetyl-alpha-D-glucosaminyl-[heparan sulfate](n) =
CC acetate + alpha-D-glucosaminyl-[heparan sulfate](n);
CC Xref=Rhea:RHEA:70587, Rhea:RHEA-COMP:9830, Rhea:RHEA-COMP:11585,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:30089, ChEBI:CHEBI:58388,
CC ChEBI:CHEBI:70974; Evidence={ECO:0000250|UniProtKB:P52848};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70588;
CC Evidence={ECO:0000250|UniProtKB:P52848};
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 Evidence={ECO:0000269|PubMed:10758005, ECO:0000269|PubMed:11087757,
CC ECO:0000269|PubMed:12590599, ECO:0000269|PubMed:12634318,
CC ECO:0000269|PubMed:16020517, ECO:0000269|PubMed:16056228,
CC ECO:0000269|PubMed:18337501};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21981;
CC Evidence={ECO:0000269|PubMed:16020517, ECO:0000269|PubMed:16056228};
CC -!- ACTIVITY REGULATION: Inhibited by long N-sulfated sequences (more than
CC 6 sugar residues) accumulating in its substrates heparan sulfate, and
CC heparin. {ECO:0000269|PubMed:12634318}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=13.3 uM for K5 polysaccharide {ECO:0000269|PubMed:12634318};
CC KM=0.35 uM for N-acetylated HS-II {ECO:0000269|PubMed:12634318};
CC -!- PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
CC {ECO:0000269|PubMed:10758005, ECO:0000269|PubMed:12590599,
CC ECO:0000269|PubMed:12634318, ECO:0000269|PubMed:16020517,
CC ECO:0000269|PubMed:16056228}.
CC -!- PATHWAY: Glycan metabolism; heparin biosynthesis.
CC {ECO:0000305|PubMed:12634318}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with heparan sulfate co-
CC polymerase subunits EXT1 and EXT2. {ECO:0000250|UniProtKB:P52848,
CC ECO:0000269|PubMed:18337501}.
CC -!- INTERACTION:
CC Q3UHN9; P70428: Ext2; NbExp=2; IntAct=EBI-15693148, EBI-15693102;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q02353}; Single-pass type II membrane protein
CC {ECO:0000255}. Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000250|UniProtKB:P52848}; Single-pass type II membrane protein
CC {ECO:0000255}. Golgi apparatus, cis-Golgi network membrane
CC {ECO:0000250|UniProtKB:P52848}; Single-pass type II membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q3UHN9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UHN9-2; Sequence=VSP_017401, VSP_017402;
CC Name=3;
CC IsoId=Q3UHN9-3; Sequence=VSP_017399, VSP_017400;
CC -!- TISSUE SPECIFICITY: Widely expressed in adult and throughout
CC development. {ECO:0000269|PubMed:11087757}.
CC -!- DISRUPTION PHENOTYPE: Mice survive until birth but are cyanotic and die
CC neonatally in a condition resembling respiratory distress syndrome. In
CC addition, a minor proportion of mice embryos die during the embryonic
CC period. Mutant mice display cerebral hypoplasia and craniofacial
CC defects, disturbed Ca(2+) kinetics in myotubes. They also display
CC deficiencies L-selectin and chemokine-mediated neutrophil trafficking
CC during inflammatory responses. {ECO:0000269|PubMed:10664446,
CC ECO:0000269|PubMed:10852901, ECO:0000269|PubMed:12692154,
CC ECO:0000269|PubMed:16020517, ECO:0000269|PubMed:16056228}.
CC -!- MISCELLANEOUS: The presence of 4 different NDST enzymes in mammals, as
CC well as differences in their enzyme activity suggest that some initiate
CC heparan sulfate modification/sulfation reactions, whereas other later
CC on fill in or extend already modified heparan sulfate sequences.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. NDST subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE41527.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF049894; AAC17228.1; -; mRNA.
DR EMBL; AF074926; AAD15980.1; -; mRNA.
DR EMBL; AK035642; BAC29136.1; -; mRNA.
DR EMBL; AK147282; BAE27818.1; -; mRNA.
DR EMBL; AK170041; BAE41527.1; ALT_FRAME; mRNA.
DR EMBL; AK171013; BAE42184.1; -; mRNA.
DR EMBL; BC066098; AAH66098.1; -; mRNA.
DR EMBL; BC079561; AAH79561.1; -; mRNA.
DR CCDS; CCDS37834.1; -. [Q3UHN9-1]
DR RefSeq; NP_001335029.1; NM_001348100.1. [Q3UHN9-1]
DR RefSeq; NP_001335030.1; NM_001348101.1. [Q3UHN9-1]
DR RefSeq; NP_001335031.1; NM_001348102.1. [Q3UHN9-1]
DR RefSeq; NP_001335032.1; NM_001348103.1. [Q3UHN9-1]
DR RefSeq; NP_001335075.1; NM_001348146.1. [Q3UHN9-2]
DR RefSeq; NP_032332.2; NM_008306.5. [Q3UHN9-1]
DR RefSeq; XP_006525730.1; XM_006525667.3.
DR RefSeq; XP_006525731.1; XM_006525668.2. [Q3UHN9-1]
DR RefSeq; XP_006525732.1; XM_006525669.3.
DR RefSeq; XP_006525733.1; XM_006525670.3.
DR RefSeq; XP_006525734.1; XM_006525671.1.
DR RefSeq; XP_011245146.1; XM_011246844.2.
DR AlphaFoldDB; Q3UHN9; -.
DR SMR; Q3UHN9; -.
DR DIP; DIP-29859N; -.
DR IntAct; Q3UHN9; 1.
DR STRING; 10090.ENSMUSP00000126623; -.
DR GlyGen; Q3UHN9; 4 sites.
DR iPTMnet; Q3UHN9; -.
DR PhosphoSitePlus; Q3UHN9; -.
DR SwissPalm; Q3UHN9; -.
DR EPD; Q3UHN9; -.
DR MaxQB; Q3UHN9; -.
DR PaxDb; Q3UHN9; -.
DR PeptideAtlas; Q3UHN9; -.
DR PRIDE; Q3UHN9; -.
DR ProteomicsDB; 252936; -. [Q3UHN9-1]
DR ProteomicsDB; 252937; -. [Q3UHN9-2]
DR ProteomicsDB; 252938; -. [Q3UHN9-3]
DR Antibodypedia; 28038; 199 antibodies from 23 providers.
DR DNASU; 15531; -.
DR Ensembl; ENSMUST00000169273; ENSMUSP00000126623; ENSMUSG00000054008. [Q3UHN9-1]
DR Ensembl; ENSMUST00000237783; ENSMUSP00000158312; ENSMUSG00000054008. [Q3UHN9-1]
DR GeneID; 15531; -.
DR KEGG; mmu:15531; -.
DR UCSC; uc008fat.1; mouse. [Q3UHN9-1]
DR UCSC; uc008fav.1; mouse. [Q3UHN9-2]
DR UCSC; uc008faw.1; mouse. [Q3UHN9-3]
DR CTD; 3340; -.
DR MGI; MGI:104719; Ndst1.
DR VEuPathDB; HostDB:ENSMUSG00000054008; -.
DR eggNOG; KOG3703; Eukaryota.
DR GeneTree; ENSGT00940000157857; -.
DR HOGENOM; CLU_011357_2_0_1; -.
DR InParanoid; Q3UHN9; -.
DR OMA; QMELRTH; -.
DR OrthoDB; 388292at2759; -.
DR PhylomeDB; Q3UHN9; -.
DR TreeFam; TF313193; -.
DR BRENDA; 2.8.2.8; 3474.
DR Reactome; R-MMU-2022928; HS-GAG biosynthesis.
DR UniPathway; UPA00756; -.
DR UniPathway; UPA00862; -.
DR BioGRID-ORCS; 15531; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Ndst1; mouse.
DR PRO; PR:Q3UHN9; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q3UHN9; protein.
DR Bgee; ENSMUSG00000054008; Expressed in right lung lobe and 266 other tissues.
DR ExpressionAtlas; Q3UHN9; baseline and differential.
DR Genevisible; Q3UHN9; MM.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
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:0032588; C:trans-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0015016; F:[heparan sulfate]-glucosamine N-sulfotransferase activity; IDA:UniProtKB.
DR GO; GO:0019213; F:deacetylase activity; IDA:MGI.
DR GO; GO:0102140; F:heparan sulfate N-deacetylase activity; IDA:UniProtKB.
DR GO; GO:0008146; F:sulfotransferase activity; IDA:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0035904; P:aorta development; IMP:MGI.
DR GO; GO:0003279; P:cardiac septum development; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0060976; P:coronary vasculature development; IMP:MGI.
DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; IMP:MGI.
DR GO; GO:0048703; P:embryonic viscerocranium morphogenesis; IMP:MGI.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IMP:MGI.
DR GO; GO:0030900; P:forebrain development; IMP:MGI.
DR GO; GO:0030203; P:glycosaminoglycan metabolic process; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; ISO:MGI.
DR GO; GO:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; IDA:UniProtKB.
DR GO; GO:0030210; P:heparin biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0030901; P:midbrain development; IGI:MGI.
DR GO; GO:0000271; P:polysaccharide biosynthetic process; IMP:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:MGI.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IGI:MGI.
DR GO; GO:0006476; P:protein deacetylation; TAS:MGI.
DR GO; GO:0006477; P:protein sulfation; IMP:MGI.
DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; IMP:MGI.
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; Inflammatory response; Membrane; Multifunctional enzyme;
KW Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..882
FT /note="Bifunctional heparan sulfate N-deacetylase/N-
FT sulfotransferase 1"
FT /id="PRO_0000225655"
FT TOPO_DOM 1..17
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 18..38
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 39..882
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 1..169
FT /note="Sufficient for localization to Golgi membrane"
FT /evidence="ECO:0000250|UniProtKB:P52848"
FT REGION 40..598
FT /note="Heparan sulfate N-deacetylase 1"
FT REGION 599..882
FT /note="Heparan sulfate N-sulfotransferase 1"
FT ACT_SITE 614
FT /note="For sulfotransferase activity"
FT /evidence="ECO:0000250|UniProtKB:P52848"
FT BINDING 614..618
FT /ligand="adenosine 3',5'-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58343"
FT /evidence="ECO:0000250|UniProtKB:P52848"
FT BINDING 712
FT /ligand="adenosine 3',5'-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58343"
FT /evidence="ECO:0000250|UniProtKB:P52848"
FT BINDING 817
FT /ligand="adenosine 3',5'-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58343"
FT /evidence="ECO:0000250|UniProtKB:P52848"
FT BINDING 833..837
FT /ligand="adenosine 3',5'-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58343"
FT /evidence="ECO:0000250|UniProtKB:P52848"
FT CARBOHYD 231
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 351
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 401
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 667
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 818..828
FT /evidence="ECO:0000250|UniProtKB:P52848"
FT VAR_SEQ 143..185
FT /note="KYVNLDAWNRELLDKYCVAYGVGIIGFFKANENSLLSAQLKGF -> SISCH
FT SSSVLQTVKGKSAAGPFAQPGRKTGHVPEGFEPGPARV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_017399"
FT VAR_SEQ 186..882
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_017400"
FT VAR_SEQ 480..495
FT /note="VLPRQTCGLFTHTIFY -> RLGDTEVKNPDKSLTS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_017401"
FT VAR_SEQ 496..882
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_017402"
FT MUTAGEN 486
FT /note="C->W: Loss of deacetylase activity. No effect on
FT sulfotransferase activity."
FT /evidence="ECO:0000269|PubMed:12590599"
FT MUTAGEN 614
FT /note="K->A: No effect on deacetylase activity. Loss of
FT sulfotransferase activity."
FT /evidence="ECO:0000269|PubMed:12590599"
FT CONFLICT 109
FT /note="F -> S (in Ref. 3; BAE27818)"
FT /evidence="ECO:0000305"
FT CONFLICT 789
FT /note="M -> V (in Ref. 1; AAC17228)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 882 AA; 100726 MW; 8BE300ABCB8E648D CRC64;
MPALACLRRL CRHLSPQAVL FLLFVFCLFS VFVSAYYLYG WNRGLEPSAD ASESDCGDPP
PVAPSRLLPI KPVQAVAPSR TDPLVLVFVE SLYSQLGQEV VAILESSRFK YRTEIAPGKG
DMPTLTDKGR GRFALIIYEN ILKYVNLDAW NRELLDKYCV AYGVGIIGFF KANENSLLSA
QLKGFPLFLH SNLGLKDCSI NPKSPLLYVT RPSEVEKGVL PGEDWTVFQS NHSTYEPVLL
AKTRSSESIP HLGADAGLHA ALHATVVQDL GLHDGIQRVL FGNNLNFWLH KLVFVDAVAF
LTGKRLSLPL DRYILVDIDD IFVGKEGTRM KVEDVKALFD TQNELRTHIP NFTFNLGYSG
KFFHTGTDAE DAGDDLLLSY VKEFWWFPHM WSHMQPHLFH NQSVLAEQMA LNKKFAVEHG
IPTDMGYAVA PHHSGVYPVH VQLYEAWKQV WGIRVTSTEE YPHLKPARYR RGFIHNGIMV
LPRQTCGLFT HTIFYNEYPG GSSELDKIIN GGELFLTVLL NPISIFMTHL SNYGNDRLGL
YTFKHLVRFL HSWTNLRLQT LPPVQLAQKY FQIFSEEKDP LWQDPCEDKR HKDIWSKEKT
CDRFPKLLII GPQKTGTTAL YLFLGMHPDL SSNYPSSETF EEIQFFNGHN YHKGIDWYME
FFPIPSNTTS DFYFEKSANY FDSEVAPRRA AALLPKAKIL SILINPADRA YSWYQHQRAH
DDPVALKYTF HEVITAGPDA SSKLRALQNR CLVPGWYATH IERWLSAFHA NQILVLDGKL
LRTEPAKVMD TVQKFLGVTS TVDYHKTLAF DPKKGFWCQL LEGGKTKCLG KSKGRKYPEM
DLDSRAFLKD YFRDHNIELS KLLYKMGQTL PTWLREDLQN TR
