NDST2_MOUSE
ID NDST2_MOUSE Reviewed; 883 AA.
AC P52850; Q3UDF4; Q549P5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 161.
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=Mndns;
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 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].
RC STRAIN=LAF1;
RX PubMed=8294485; DOI=10.1016/s0021-9258(17)42164-8;
RA Orellana A., Hirschberg C.B., Wei Z., Swiedler S.J., Ishihara M.;
RT "Molecular cloning and expression of a glycosaminoglycan N-
RT acetylglucosaminyl N-deacetylase/N-sulfotransferase from a heparin-
RT producing cell line.";
RL J. Biol. Chem. 269:2270-2276(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 360-375; 568-580;
RP 697-710 AND 813-823.
RC STRAIN=Leaden X A1;
RX PubMed=8144627; DOI=10.1016/s0021-9258(17)34079-6;
RA Eriksson I., Sandbaeck D., Ek B., Lindahl U., Kjellen L.;
RT "cDNA cloning and sequencing of mouse mastocytoma glucosaminyl N-
RT deacetylase/N-sulfotransferase, an enzyme involved in the biosynthesis of
RT heparin.";
RL J. Biol. Chem. 269:10438-10443(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10466726; DOI=10.1038/23481;
RA Humphries D.E., Wong G.W., Friend D.S., Gurish M.F., Qiu W.-T., Huang C.,
RA Sharpe A.H., Stevens R.L.;
RT "Heparin is essential for the storage of specific granule proteases in mast
RT cells.";
RL Nature 400:769-772(1999).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10466727; DOI=10.1038/23488;
RA Forsberg E., Pejler G., Ringvall M., Lunderius C., Tomasini-Johansson B.,
RA Kusche-Gullberg M., Eriksson I., Ledin J., Hellman L., Kjellen L.;
RT "Abnormal mast cells in mice deficient in a heparin-synthesizing enzyme.";
RL Nature 400:773-776(1999).
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 determining the extent and pattern of sulfation of
CC heparan sulfate. Required for the exosomal release of SDCBP, CD63 and
CC syndecan (By similarity). {ECO:0000250|UniProtKB:P52849,
CC ECO:0000269|PubMed:10466726, ECO:0000269|PubMed:10466727}.
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 -!- TISSUE SPECIFICITY: Widely expressed in adult and throughout
CC development.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile but have fewer
CC connective-tissue-type mast cells; mast cells that remain having an
CC altered morphology and severely reduced amounts of stored histamine and
CC mast cell proteases. {ECO:0000269|PubMed:10466726,
CC ECO:0000269|PubMed:10466727}.
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}.
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; U02304; AAC52137.1; -; mRNA.
DR EMBL; X75885; CAA53479.1; -; mRNA.
DR EMBL; AF074925; AAD15979.1; -; mRNA.
DR EMBL; AK150100; BAE29307.1; -; mRNA.
DR EMBL; BC110480; AAI10481.1; -; mRNA.
DR CCDS; CCDS26854.1; -.
DR PIR; A49733; A49733.
DR RefSeq; NP_034941.2; NM_010811.2.
DR AlphaFoldDB; P52850; -.
DR SMR; P52850; -.
DR STRING; 10090.ENSMUSP00000040227; -.
DR GlyGen; P52850; 6 sites.
DR iPTMnet; P52850; -.
DR PhosphoSitePlus; P52850; -.
DR MaxQB; P52850; -.
DR PaxDb; P52850; -.
DR PRIDE; P52850; -.
DR ProteomicsDB; 253041; -.
DR DNASU; 17423; -.
DR Ensembl; ENSMUST00000047490; ENSMUSP00000040227; ENSMUSG00000039308.
DR Ensembl; ENSMUST00000223679; ENSMUSP00000153036; ENSMUSG00000039308.
DR Ensembl; ENSMUST00000225000; ENSMUSP00000153141; ENSMUSG00000039308.
DR GeneID; 17423; -.
DR KEGG; mmu:17423; -.
DR UCSC; uc007sks.1; mouse.
DR CTD; 8509; -.
DR MGI; MGI:97040; Ndst2.
DR VEuPathDB; HostDB:ENSMUSG00000039308; -.
DR eggNOG; KOG3703; Eukaryota.
DR GeneTree; ENSGT00940000156237; -.
DR HOGENOM; CLU_011357_2_0_1; -.
DR InParanoid; P52850; -.
DR OMA; EMHLNYA; -.
DR OrthoDB; 388292at2759; -.
DR PhylomeDB; P52850; -.
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; 17423; 6 hits in 71 CRISPR screens.
DR ChiTaRS; Ndst2; mouse.
DR PRO; PR:P52850; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P52850; protein.
DR Bgee; ENSMUSG00000039308; Expressed in retinal neural layer and 215 other tissues.
DR ExpressionAtlas; P52850; baseline and differential.
DR Genevisible; P52850; MM.
DR GO; GO:0005794; C:Golgi apparatus; IDA:BHF-UCL.
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; 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:0006024; P:glycosaminoglycan biosynthetic process; TAS: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; IDA:UniProtKB.
DR GO; GO:0030210; P:heparin biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0002448; P:mast cell mediated immunity; IMP:MGI.
DR GO; GO:0002002; P:regulation of angiotensin levels in blood; 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 Direct protein sequencing; Disulfide bond; Glycoprotein; Golgi apparatus;
KW Hydrolase; Membrane; Multifunctional enzyme; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..883
FT /note="Bifunctional heparan sulfate N-deacetylase/N-
FT sulfotransferase 2"
FT /id="PRO_0000085213"
FT TOPO_DOM 1..18
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 19..39
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 40..883
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 41..597
FT /note="Heparan sulfate N-deacetylase 2"
FT REGION 49..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 598..883
FT /note="Heparan sulfate N-sulfotransferase 2"
FT COMPBIAS 64..79
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 613
FT /note="For sulfotransferase activity"
FT /evidence="ECO:0000250"
FT BINDING 613..617
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 711
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 832..836
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT CARBOHYD 233
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 400
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 666
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 726
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 802
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 817..827
FT /evidence="ECO:0000250"
FT CONFLICT 118
FT /note="A -> V (in Ref. 2; CAA53479)"
FT /evidence="ECO:0000305"
FT CONFLICT 396
FT /note="Missing (in Ref. 2; CAA53479)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="P -> L (in Ref. 4; BAE29307)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 883 AA; 101202 MW; 8AC8C7BEF5B8EED8 CRC64;
MLQLWKVVRP ARQLELHRLI LLLIGFSLVS MGFLAYYVST SPKAKEPLPL PLGDCSSSGA
AGPGPARPPV PPRPQRPPET TRTEPVVLVF VESAYSQLGQ EIVAILESSR FRYSTELAPG
RGDMPTLTDH THGRYVLVIY ENLLKYVNLD AWSRELLDRY CVEYGVGIIG FFRAREHSLL
SAQLKGFPLF LHSNLGLRDY QVNPSAPLLH LTRPSRLEPG PLPGDDWTIF QSNHSTYEPV
LIASHRPAEL SMPGPVLRRA RLPTVVQDLG LHDGIQRVLF GHGLSFWLHK LVFVDAVAYL
TGKRLCLDLD RYILVDIDDI FVGKEGTRMK VADVEALLTT QNKLRTLVPN FTFNLGFSGK
FYHTGTEEED AGDDMLLKHR REFWWFPHMW SHMQPHLFHN RSVLADQMRL NKQFALEHGI
PTDLGYAVAP HHSGVYPIHS QLYEAWKSVW GIQVTSTEEY PHLRPARYRR GFIHNGIMVL
PRQTCGLFTH TIFYNEYPGG SRELDRSIRG GELFLTVLLN PISVFMTHLS NYGNDRLGLY
TFESLVRFLQ CWTRLRLQTL PPVPLAQKYF ELFPQERSPL WQNPCDDKRH KDIWSKEKTC
DRLPKFLIVG PQKTGTTAIH FFLSLHPAVT SSFPSPSTFE EIQFFNGPNY HKGIDWYMDF
FPVPSNASTD FLFEKSATYF DSEVVPRRGA ALLPRAKIIT VLINPADRAY SWYQHQRAHG
DPIALNYTFY QVISASSQAP LLLRSLQNRC LVPGYYSTHL QRWLTYYPSG QLLIMDGQEL
RVNPAASMEI IQKFLGITPF LNYTRTLRFD EDKGFWCQGL EGGKTRCLGR SKGRRYPDMD
MESRLFLTDF FRNHNLELSK LLSRLGQPAP LWLREELQHS SVG
