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Protein

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1

Gene

Ndst1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan, a prerequisite substrate for later modifications in heparin biosynthesis. Plays a role in determining the extent and pattern of sulfation of heparan sulfate. Compared to other NDST enzymes, its presence is absolutely required. Participates in biosynthesis of heparan sulfate that can ultimately serve as L-selectin ligands, thereby playing a role in inflammatory response. Required for the exosomal release of SDCBP, CD63 and syndecan.By similarity

Catalytic activityi

3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine = adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine.

Kineticsi

  1. KM=144 µM for K5 polysaccharide (for deacetylase activity)1 Publication
  2. KM=160 µM for K5 polysaccharide (for sulfotransferase activity)1 Publication
  1. Vmax=40 µmol/min/mg enzyme with K5 polysaccharide as substrate (for deacetylase activity)1 Publication
  2. Vmax=2104 µmol/min/mg enzyme with K5 polysaccharide as substrate (for sulfotransferase activity)1 Publication

Pathwayi: heparan sulfate biosynthesis

This protein is involved in the pathway heparan sulfate biosynthesis, which is part of Glycan metabolism.
View all proteins of this organism that are known to be involved in the pathway heparan sulfate biosynthesis and in Glycan metabolism.

Pathwayi: heparin biosynthesis

This protein is involved in the pathway heparin biosynthesis, which is part of Glycan metabolism.
View all proteins of this organism that are known to be involved in the pathway heparin biosynthesis and in Glycan metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei614For sulfotransferase activityBy similarity1
Binding sitei712PAPSBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi614 – 618PAPSBy similarity5
Nucleotide bindingi833 – 837PAPSBy similarity5

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Transferase

Keywords - Biological processi

Inflammatory response

Enzyme and pathway databases

BRENDAi2.8.2.8. 5301.
ReactomeiR-RNO-2022928. HS-GAG biosynthesis.
SABIO-RKQ02353.
UniPathwayiUPA00756.
UPA00862.

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1 (EC:2.8.2.8)
Alternative name(s):
Glucosaminyl N-deacetylase/N-sulfotransferase 1
Short name:
NDST-1
N-heparan sulfate sulfotransferase 1
Short name:
N-HSST 1
[Heparan sulfate]-glucosamine N-sulfotransferase 1
Short name:
HSNST 1
Including the following 2 domains:
Heparan sulfate N-deacetylase 1 (EC:3.-.-.-)
Heparan sulfate N-sulfotransferase 1 (EC:2.8.2.-)
Gene namesi
Name:Ndst1
Synonyms:Hsst, Hsst1, Ndanst
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 18

Organism-specific databases

RGDi69303. Ndst1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 17CytoplasmicSequence analysisAdd BLAST17
Transmembranei18 – 39Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST22
Topological domaini40 – 882LumenalSequence analysisAdd BLAST843

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi56C → A: Induces a reduction in sulfotransferase activity but does not affect deacetylase activity. 1 Publication1
Mutagenesisi159C → A: Induces a reduction in sulfotransferase activity but increases deacetylase activity. 1 Publication1
Mutagenesisi486C → A or V: Does not affect sulfotransferase activity but increases deacetylase activity. 1 Publication1
Mutagenesisi486C → F: Does not affect sulfotransferase activity but strongly decreases deacetylase activity. 1 Publication1
Mutagenesisi486C → G: Does not affect sulfotransferase activity but weakly affects deacetylase activity. 1 Publication1
Mutagenesisi486C → R or W: Does not affect sulfotransferase activity but abolishes deacetylase activity. 1 Publication1
Mutagenesisi586C → A: Loss of deacetylase and sulfotransferase activities. 1 Publication1
Mutagenesisi601C → A: Loss of sulfotransferase activity but does not affect deacetylase activity. 1 Publication1
Mutagenesisi751C → A: Does not affect neither deacetylase nor sulfotransferase activities. 1 Publication1
Mutagenesisi818C → A: Loss of sulfotransferase activity but does not affect deacetylase activity. 1 Publication1
Mutagenesisi828C → A: Loss of sulfotransferase activity but does not affect deacetylase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000852111 – 882Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1Add BLAST882

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi231N-linked (GlcNAc...)Sequence analysis1
Glycosylationi351N-linked (GlcNAc...)Sequence analysis1
Glycosylationi401N-linked (GlcNAc...)Sequence analysis1
Glycosylationi667N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi818 ↔ 828By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ02353.
PRIDEiQ02353.

Expressioni

Gene expression databases

BgeeiENSRNOG00000019014.
GenevisibleiQ02353. RN.

Interactioni

Subunit structurei

Monomer. Interacts with EXT2.By similarity

Protein-protein interaction databases

MINTiMINT-4564880.
STRINGi10116.ENSRNOP00000025881.

Structurei

3D structure databases

ProteinModelPortaliQ02353.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni40 – 598Heparan sulfate N-deacetylase 1Add BLAST559
Regioni599 – 882Heparan sulfate N-sulfotransferase 1Add BLAST284

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3703. Eukaryota.
ENOG410XQN4. LUCA.
GeneTreeiENSGT00760000119023.
HOGENOMiHOG000008010.
HOVERGENiHBG082011.
InParanoidiQ02353.
KOiK02576.
OMAiTNTIDYH.
OrthoDBiEOG091G02CP.
PhylomeDBiQ02353.
TreeFamiTF313193.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR021930. Heparan_SO4_deacetylase.
IPR027417. P-loop_NTPase.
IPR000863. Sulfotransferase_dom.
[Graphical view]
PfamiPF12062. HSNSD. 1 hit.
PF00685. Sulfotransfer_1. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.

Sequencei

Sequence statusi: Complete.

Q02353-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPALACLRRL CRHLSPQAVL FLLFVFCLFS VFVSAYYLYG WNRGLEPSAD
60 70 80 90 100
ASESDCGDPP PVAPSRLLPI KPVQAVAPSR TDPLVLVFVE SLYSQLGQEV
110 120 130 140 150
VAILESSRFK YRTEIAPGKG DMPTLTDKGR GRFALIIYEN ILKYVNLDAW
160 170 180 190 200
NRELLDKYCV AYGVGIIGFF KANENSLLSA QLKGFPLFLH SNLGLKDCSI
210 220 230 240 250
NPKSPLLYVT RPSEVEKGVL PGEDWTVFQS NHSTYEPVLL AKTRSSESIP
260 270 280 290 300
HLGADAGLHA ALHATVVQDL GLHDGIQRVL FGNNLNFWLH KLVFVDAVAF
310 320 330 340 350
LTGKRLSLPL DRYILVDIDD IFVGKEGTRM KVEDVKALFD TQNELRTHIP
360 370 380 390 400
NFTFNLGYSG KFFHTGTDAE DAGDDLLLSY VKEFWWFPHM WSHMQPHLFH
410 420 430 440 450
NQSVLAEQMA LNKKFAVEHG IPTDMGYAVA PHHSGVYPVH VQLYEAWKQV
460 470 480 490 500
WNIRVTSTEE YPHLKPARYR RGFIHNGIMV LPRQTCGLFT HTIFYNEYPG
510 520 530 540 550
GSSELDKIIN GGELFLTVLL NPISVFMTHL SNYGNDRLGL YTFKHLVRFL
560 570 580 590 600
HSWTNLRLQT LPPVQLAQKY FQIFSEEKDP LWQDPCEDKR HKDIWSKEKT
610 620 630 640 650
CDRFPKLLII GPQKTGTTAL YLFLGMHPDL SSNYPSSETF EEIQFFNGHN
660 670 680 690 700
YHKGIDWYME FFPIPSNTTS DFYFEKSANY FDSEVAPRRA AALLPKAKVL
710 720 730 740 750
TILINPADRA YSWYQHQRAH DDPVALKYTF HEVITAGPDA SSKLRALQNR
760 770 780 790 800
CLVPGWYATH IERWLSAFHA NQILVLDGKL LRTEPAKVMD TVQKFLGVTS
810 820 830 840 850
TVDYHKTLAF DPKKGFWCQL LEGGKTKCLG KSKGRKYPEM DLDSRAFLKD
860 870 880
YYRDHNIELS KLLYKMGQTL PTWLREDLQN TR
Length:882
Mass (Da):100,785
Last modified:July 1, 1993 - v1
Checksum:iF3AB9263EF6E4345
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M92042 mRNA. Translation: AAA41701.1.
PIRiA42855.
RefSeqiNP_077337.1. NM_024361.1.
XP_017456417.1. XM_017600928.1.
XP_017456418.1. XM_017600929.1.
XP_017456419.1. XM_017600930.1.
XP_017456420.1. XM_017600931.1.
XP_017456421.1. XM_017600932.1.
XP_017456422.1. XM_017600933.1.
UniGeneiRn.9705.

Genome annotation databases

EnsembliENSRNOT00000025881; ENSRNOP00000025881; ENSRNOG00000019014.
GeneIDi29633.
KEGGirno:29633.
UCSCiRGD:69303. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M92042 mRNA. Translation: AAA41701.1.
PIRiA42855.
RefSeqiNP_077337.1. NM_024361.1.
XP_017456417.1. XM_017600928.1.
XP_017456418.1. XM_017600929.1.
XP_017456419.1. XM_017600930.1.
XP_017456420.1. XM_017600931.1.
XP_017456421.1. XM_017600932.1.
XP_017456422.1. XM_017600933.1.
UniGeneiRn.9705.

3D structure databases

ProteinModelPortaliQ02353.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4564880.
STRINGi10116.ENSRNOP00000025881.

Proteomic databases

PaxDbiQ02353.
PRIDEiQ02353.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000025881; ENSRNOP00000025881; ENSRNOG00000019014.
GeneIDi29633.
KEGGirno:29633.
UCSCiRGD:69303. rat.

Organism-specific databases

CTDi3340.
RGDi69303. Ndst1.

Phylogenomic databases

eggNOGiKOG3703. Eukaryota.
ENOG410XQN4. LUCA.
GeneTreeiENSGT00760000119023.
HOGENOMiHOG000008010.
HOVERGENiHBG082011.
InParanoidiQ02353.
KOiK02576.
OMAiTNTIDYH.
OrthoDBiEOG091G02CP.
PhylomeDBiQ02353.
TreeFamiTF313193.

Enzyme and pathway databases

UniPathwayiUPA00756.
UPA00862.
BRENDAi2.8.2.8. 5301.
ReactomeiR-RNO-2022928. HS-GAG biosynthesis.
SABIO-RKQ02353.

Miscellaneous databases

PROiQ02353.

Gene expression databases

BgeeiENSRNOG00000019014.
GenevisibleiQ02353. RN.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR021930. Heparan_SO4_deacetylase.
IPR027417. P-loop_NTPase.
IPR000863. Sulfotransferase_dom.
[Graphical view]
PfamiPF12062. HSNSD. 1 hit.
PF00685. Sulfotransfer_1. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNDST1_RAT
AccessioniPrimary (citable) accession number: Q02353
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: November 30, 2016
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The presence of 4 different heparan sulfate N-deacetylase/N-sulfotransferase enzymes in mammals, as well as differences in their enzyme activity suggest that some initiate heparan sulfate modification/sulfation reactions, whereas other later on fill in or extend already modified heparan sulfate sequences.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.