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 27-MAR-2024, entry version 144. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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.ENSMUSP00000158312; -. DR GlyCosmos; Q3UHN9; 4 sites, No reported glycans. DR GlyGen; Q3UHN9; 4 sites. DR iPTMnet; Q3UHN9; -. DR PhosphoSitePlus; Q3UHN9; -. DR SwissPalm; Q3UHN9; -. DR EPD; Q3UHN9; -. DR MaxQB; Q3UHN9; -. DR PaxDb; 10090-ENSMUSP00000126623; -. DR PeptideAtlas; Q3UHN9; -. DR ProteomicsDB; 252936; -. [Q3UHN9-1] DR ProteomicsDB; 252937; -. [Q3UHN9-2] DR ProteomicsDB; 252938; -. [Q3UHN9-3] DR Pumba; Q3UHN9; -. DR Antibodypedia; 28038; 224 antibodies from 24 providers. DR DNASU; 15531; -. DR Ensembl; ENSMUST00000169273.2; ENSMUSP00000126623.2; ENSMUSG00000054008.10. [Q3UHN9-1] DR Ensembl; ENSMUST00000237783.2; ENSMUSP00000158312.2; ENSMUSG00000054008.10. [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 AGR; MGI:104719; -. 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; VGPDCDE; -. DR OrthoDB; 2913264at2759; -. 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 77 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 268 other cell types or tissues. DR ExpressionAtlas; Q3UHN9; baseline and differential. DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. 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:0050119; F:N-acetylglucosamine deacetylase activity; IDA:MGI. 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; IDA: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:0007585; P:respiratory gaseous exchange by respiratory system; IMP:MGI. 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:SF30; BIFUNCTIONAL HEPARAN SULFATE N-DEACETYLASE_N-SULFOTRANSFERASE 1; 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. DR Genevisible; Q3UHN9; MM. 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 //