NDST1_RAT
ID NDST1_RAT Reviewed; 882 AA.
AC Q02353;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1 {ECO:0000305|PubMed:8483907};
DE AltName: Full=Glucosaminyl N-deacetylase/N-sulfotransferase 1;
DE Short=NDST-1;
DE AltName: Full=Golgi heparan sulfate N-deacetylase/N-sulfotransferase {ECO:0000303|PubMed:8483907};
DE AltName: Full=N-heparan sulfate sulfotransferase 1;
DE Short=N-HSST {ECO:0000303|PubMed:1379236};
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:8483907, ECO:0000269|PubMed:9890952};
DE Includes:
DE RecName: Full=Heparan sulfate N-sulfotransferase 1;
DE EC=2.8.2.8 {ECO:0000269|PubMed:1379236, ECO:0000269|PubMed:3422231, ECO:0000269|PubMed:8483907, ECO:0000269|PubMed:9890952};
GN Name=Ndst1 {ECO:0000312|RGD:69303}; Synonyms=Hsst, Hsst1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC
RP ACTIVITY, AND PATHWAY.
RC TISSUE=Liver;
RX PubMed=1379236; DOI=10.1016/s0021-9258(19)49598-7;
RA Hashimoto Y., Orellana A., Gil G., Hirschberg C.B.;
RT "Molecular cloning and expression of rat liver N-heparan sulfate
RT sulfotransferase.";
RL J. Biol. Chem. 267:15744-15750(1992).
RN [2]
RP IDENTIFICATION, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=3422231; DOI=10.1016/s0021-9258(18)69223-3;
RA Brandan E., Hirschberg C.B.;
RT "Purification of rat liver N-heparan-sulfate sulfotransferase.";
RL J. Biol. Chem. 263:2417-2422(1988).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=8483907; DOI=10.1073/pnas.90.9.3885;
RA Wei Z., Swiedler S.J., Ishihara M., Orellana A., Hirschberg C.B.;
RT "A single protein catalyzes both N-deacetylation and N-sulfation during the
RT biosynthesis of heparan sulfate.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:3885-3889(1993).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF
RP CYS-56; CYS-159; CYS-486; CYS-586; CYS-601; CYS-751; CYS-818 AND CYS-828,
RP AND DISULFIDE BOND.
RX PubMed=9890952; DOI=10.1074/jbc.274.4.1966;
RA Wei Z., Swiedler S.J.;
RT "Functional analysis of conserved cysteines in heparan sulfate N-
RT deacetylase-N-sulfotransferases.";
RL J. Biol. Chem. 274:1966-1970(1999).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=11792394; DOI=10.1016/s0022-1759(01)00546-4;
RA Mura C.V., Becker M.I., Orellana A., Wolff D.;
RT "Immunopurification of Golgi vesicles by magnetic sorting.";
RL J. Immunol. Methods 260:263-271(2002).
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:1379236, PubMed:3422231,
CC PubMed:8483907, PubMed:9890952). Modifies the GlcNAc-GlcA disaccharide
CC repeating sugar backbone to make N-sulfated heparosan, a prerequisite
CC substrate for later modifications in heparin biosynthesis
CC (PubMed:1379236, PubMed:3422231). Plays a role in determining the
CC extent and pattern of sulfation of heparan sulfate. Participates in
CC biosynthesis of heparan sulfate that can ultimately serve as L-selectin
CC ligands, thereby playing a role in inflammatory response (By
CC similarity). Required for the exosomal release of SDCBP, CD63 and
CC syndecan (By similarity). {ECO:0000250|UniProtKB:P52848,
CC ECO:0000250|UniProtKB:Q3UHN9, ECO:0000269|PubMed:1379236,
CC ECO:0000269|PubMed:3422231, ECO:0000269|PubMed:8483907,
CC ECO:0000269|PubMed:9890952}.
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; Evidence={ECO:0000269|PubMed:1379236,
CC ECO:0000269|PubMed:3422231, ECO:0000269|PubMed:8483907,
CC ECO:0000269|PubMed:9890952};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21981;
CC Evidence={ECO:0000305|PubMed:1379236};
CC -!- ACTIVITY REGULATION: The deacetylase activity is specifically inhibited
CC by N-Ethylmaleimide (PubMed:8483907). The sulfotransferase activity is
CC specifically inhibited by 3',5'-ADP (PubMed:8483907).
CC {ECO:0000269|PubMed:8483907}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=144 uM for K5 polysaccharide (for deacetylase activity)
CC {ECO:0000269|PubMed:9890952};
CC KM=160 uM for K5 polysaccharide (for sulfotransferase activity)
CC {ECO:0000269|PubMed:9890952};
CC Vmax=40 umol/min/mg enzyme with K5 polysaccharide as substrate (for
CC deacetylase activity) {ECO:0000269|PubMed:9890952};
CC Vmax=2104 umol/min/mg enzyme with K5 polysaccharide as substrate (for
CC sulfotransferase activity) {ECO:0000269|PubMed:9890952};
CC -!- PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
CC {ECO:0000269|PubMed:1379236, ECO:0000269|PubMed:3422231}.
CC -!- PATHWAY: Glycan metabolism; heparin biosynthesis.
CC {ECO:0000305|PubMed:1379236, ECO:0000305|PubMed:3422231}.
CC -!- SUBUNIT: Monomer. Interacts with heparan sulfate co-polymerase subunits
CC EXT1 and EXT2. {ECO:0000250|UniProtKB:P52848,
CC ECO:0000250|UniProtKB:Q3UHN9}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:11792394}; 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 -!- 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; M92042; AAA41701.1; -; mRNA.
DR PIR; A42855; A42855.
DR RefSeq; NP_077337.1; NM_024361.1.
DR RefSeq; XP_017456417.1; XM_017600928.1.
DR RefSeq; XP_017456418.1; XM_017600929.1.
DR RefSeq; XP_017456419.1; XM_017600930.1.
DR RefSeq; XP_017456420.1; XM_017600931.1.
DR RefSeq; XP_017456421.1; XM_017600932.1.
DR RefSeq; XP_017456422.1; XM_017600933.1.
DR AlphaFoldDB; Q02353; -.
DR SMR; Q02353; -.
DR STRING; 10116.ENSRNOP00000025881; -.
DR GlyGen; Q02353; 4 sites.
DR PaxDb; Q02353; -.
DR Ensembl; ENSRNOT00000025881; ENSRNOP00000025881; ENSRNOG00000019014.
DR GeneID; 29633; -.
DR KEGG; rno:29633; -.
DR UCSC; RGD:69303; rat.
DR CTD; 3340; -.
DR RGD; 69303; Ndst1.
DR eggNOG; KOG3703; Eukaryota.
DR GeneTree; ENSGT00940000157857; -.
DR HOGENOM; CLU_011357_2_0_1; -.
DR InParanoid; Q02353; -.
DR OMA; QMELRTH; -.
DR OrthoDB; 388292at2759; -.
DR PhylomeDB; Q02353; -.
DR TreeFam; TF313193; -.
DR BRENDA; 2.8.2.8; 5301.
DR Reactome; R-RNO-2022928; HS-GAG biosynthesis.
DR SABIO-RK; Q02353; -.
DR UniPathway; UPA00756; -.
DR UniPathway; UPA00862; -.
DR PRO; PR:Q02353; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000019014; Expressed in lung and 18 other tissues.
DR Genevisible; Q02353; RN.
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; ISO:RGD.
DR GO; GO:0102140; F:heparan sulfate N-deacetylase activity; IDA:UniProtKB.
DR GO; GO:0008146; F:sulfotransferase activity; ISO:RGD.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR GO; GO:0035904; P:aorta development; ISO:RGD.
DR GO; GO:0003279; P:cardiac septum development; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0060976; P:coronary vasculature development; ISO:RGD.
DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; ISO:RGD.
DR GO; GO:0048703; P:embryonic viscerocranium morphogenesis; ISO:RGD.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0030203; P:glycosaminoglycan metabolic process; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IMP:UniProtKB.
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; ISO:RGD.
DR GO; GO:0000271; P:polysaccharide biosynthetic process; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; ISO:RGD.
DR GO; GO:0006477; P:protein sulfation; ISO:RGD.
DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; ISO:RGD.
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; 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_0000085211"
FT TOPO_DOM 1..17
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 18..39
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 40..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:0000305|PubMed:9890952"
FT MUTAGEN 56
FT /note="C->A: Induces a reduction in sulfotransferase
FT activity but does not affect deacetylase activity."
FT /evidence="ECO:0000269|PubMed:9890952"
FT MUTAGEN 159
FT /note="C->A: Induces a reduction in sulfotransferase
FT activity but increases deacetylase activity."
FT /evidence="ECO:0000269|PubMed:9890952"
FT MUTAGEN 486
FT /note="C->A,V: Does not affect sulfotransferase activity
FT but increases deacetylase activity."
FT /evidence="ECO:0000269|PubMed:9890952"
FT MUTAGEN 486
FT /note="C->F: Does not affect sulfotransferase activity but
FT strongly decreases deacetylase activity."
FT /evidence="ECO:0000269|PubMed:9890952"
FT MUTAGEN 486
FT /note="C->G: Does not affect sulfotransferase activity but
FT weakly affects deacetylase activity."
FT /evidence="ECO:0000269|PubMed:9890952"
FT MUTAGEN 486
FT /note="C->R,W: Does not affect sulfotransferase activity
FT but abolishes deacetylase activity."
FT /evidence="ECO:0000269|PubMed:9890952"
FT MUTAGEN 586
FT /note="C->A: Loss of deacetylase and sulfotransferase
FT activities."
FT /evidence="ECO:0000269|PubMed:9890952"
FT MUTAGEN 601
FT /note="C->A: Loss of sulfotransferase activity but does not
FT affect deacetylase activity."
FT /evidence="ECO:0000269|PubMed:9890952"
FT MUTAGEN 751
FT /note="C->A: Does not affect neither deacetylase nor
FT sulfotransferase activities."
FT /evidence="ECO:0000269|PubMed:9890952"
FT MUTAGEN 818
FT /note="C->A: Loss of sulfotransferase activity but does not
FT affect deacetylase activity."
FT /evidence="ECO:0000269|PubMed:9890952"
FT MUTAGEN 828
FT /note="C->A: Loss of sulfotransferase activity but does not
FT affect deacetylase activity."
FT /evidence="ECO:0000269|PubMed:9890952"
SQ SEQUENCE 882 AA; 100785 MW; F3AB9263EF6E4345 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 WNIRVTSTEE YPHLKPARYR RGFIHNGIMV
LPRQTCGLFT HTIFYNEYPG GSSELDKIIN GGELFLTVLL NPISVFMTHL SNYGNDRLGL
YTFKHLVRFL HSWTNLRLQT LPPVQLAQKY FQIFSEEKDP LWQDPCEDKR HKDIWSKEKT
CDRFPKLLII GPQKTGTTAL YLFLGMHPDL SSNYPSSETF EEIQFFNGHN YHKGIDWYME
FFPIPSNTTS DFYFEKSANY FDSEVAPRRA AALLPKAKVL TILINPADRA YSWYQHQRAH
DDPVALKYTF HEVITAGPDA SSKLRALQNR CLVPGWYATH IERWLSAFHA NQILVLDGKL
LRTEPAKVMD TVQKFLGVTS TVDYHKTLAF DPKKGFWCQL LEGGKTKCLG KSKGRKYPEM
DLDSRAFLKD YYRDHNIELS KLLYKMGQTL PTWLREDLQN TR
