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Protein

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2

Gene

Ndst2

Organism
Mus musculus (Mouse)
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. Required for the exosomal release of SDCBP, CD63 and syndecan (By similarity).By similarity2 Publications

Catalytic activityi

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

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 sitei613For sulfotransferase activityBy similarity1
Binding sitei711PAPSBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi613 – 617PAPSBy similarity5
Nucleotide bindingi832 – 836PAPSBy similarity5

GO - Molecular functioni

  • [heparan sulfate]-glucosamine N-sulfotransferase activity Source: MGI
  • deacetylase activity Source: MGI
  • sulfotransferase activity Source: MGI

GO - Biological processi

  • cellular process Source: MGI
  • glycosaminoglycan biosynthetic process Source: MGI
  • heparan sulfate proteoglycan biosynthetic process Source: MGI
  • heparin biosynthetic process Source: UniProtKB-UniPathway
  • regulation of angiotensin levels in blood Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Transferase

Enzyme and pathway databases

BRENDAi2.8.2.8. 3474.
ReactomeiR-MMU-2022928. HS-GAG biosynthesis.
UniPathwayiUPA00756.
UPA00862.

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2 (EC:2.8.2.8)
Alternative name(s):
Glucosaminyl N-deacetylase/N-sulfotransferase 2
Short name:
NDST-2
Mndns
N-heparan sulfate sulfotransferase 2
Short name:
N-HSST 2
Including the following 2 domains:
Heparan sulfate N-deacetylase 2 (EC:3.-.-.-)
Heparan sulfate N-sulfotransferase 2 (EC:2.8.2.-)
Gene namesi
Name:Ndst2
Synonyms:Hsst2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:97040. Ndst2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 18CytoplasmicSequence analysisAdd BLAST18
Transmembranei19 – 39Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini40 – 883LumenalSequence analysisAdd BLAST844

GO - Cellular componenti

  • Golgi apparatus Source: BHF-UCL
  • Golgi membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice are viable and fertile but have fewer connective-tissue-type mast cells; mast cells that remain having an altered morphology and severely reduced amounts of stored histamine and mast cell proteases.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000852131 – 883Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2Add BLAST883

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi233N-linked (GlcNAc...)Sequence analysis1
Glycosylationi350N-linked (GlcNAc...)Sequence analysis1
Glycosylationi400N-linked (GlcNAc...)Sequence analysis1
Glycosylationi666N-linked (GlcNAc...)Sequence analysis1
Glycosylationi726N-linked (GlcNAc...)Sequence analysis1
Glycosylationi802N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi817 ↔ 827By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP52850.
PRIDEiP52850.

PTM databases

PhosphoSitePlusiP52850.

Expressioni

Tissue specificityi

Widely expressed in adult and throughout development.

Gene expression databases

BgeeiENSMUSG00000039308.
GenevisibleiP52850. MM.

Interactioni

Subunit structurei

Monomer.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000040227.

Structurei

3D structure databases

ProteinModelPortaliP52850.
SMRiP52850.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni41 – 597Heparan sulfate N-deacetylase 2Add BLAST557
Regioni598 – 883Heparan sulfate N-sulfotransferase 2Add BLAST286

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3703. Eukaryota.
ENOG410XQN4. LUCA.
GeneTreeiENSGT00760000119023.
HOGENOMiHOG000008010.
HOVERGENiHBG082011.
InParanoidiP52850.
KOiK02577.
OMAiDKYLNMD.
OrthoDBiEOG091G02CP.
PhylomeDBiP52850.
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.

P52850-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLQLWKVVRP ARQLELHRLI LLLIGFSLVS MGFLAYYVST SPKAKEPLPL
60 70 80 90 100
PLGDCSSSGA AGPGPARPPV PPRPQRPPET TRTEPVVLVF VESAYSQLGQ
110 120 130 140 150
EIVAILESSR FRYSTELAPG RGDMPTLTDH THGRYVLVIY ENLLKYVNLD
160 170 180 190 200
AWSRELLDRY CVEYGVGIIG FFRAREHSLL SAQLKGFPLF LHSNLGLRDY
210 220 230 240 250
QVNPSAPLLH LTRPSRLEPG PLPGDDWTIF QSNHSTYEPV LIASHRPAEL
260 270 280 290 300
SMPGPVLRRA RLPTVVQDLG LHDGIQRVLF GHGLSFWLHK LVFVDAVAYL
310 320 330 340 350
TGKRLCLDLD RYILVDIDDI FVGKEGTRMK VADVEALLTT QNKLRTLVPN
360 370 380 390 400
FTFNLGFSGK FYHTGTEEED AGDDMLLKHR REFWWFPHMW SHMQPHLFHN
410 420 430 440 450
RSVLADQMRL NKQFALEHGI PTDLGYAVAP HHSGVYPIHS QLYEAWKSVW
460 470 480 490 500
GIQVTSTEEY PHLRPARYRR GFIHNGIMVL PRQTCGLFTH TIFYNEYPGG
510 520 530 540 550
SRELDRSIRG GELFLTVLLN PISVFMTHLS NYGNDRLGLY TFESLVRFLQ
560 570 580 590 600
CWTRLRLQTL PPVPLAQKYF ELFPQERSPL WQNPCDDKRH KDIWSKEKTC
610 620 630 640 650
DRLPKFLIVG PQKTGTTAIH FFLSLHPAVT SSFPSPSTFE EIQFFNGPNY
660 670 680 690 700
HKGIDWYMDF FPVPSNASTD FLFEKSATYF DSEVVPRRGA ALLPRAKIIT
710 720 730 740 750
VLINPADRAY SWYQHQRAHG DPIALNYTFY QVISASSQAP LLLRSLQNRC
760 770 780 790 800
LVPGYYSTHL QRWLTYYPSG QLLIMDGQEL RVNPAASMEI IQKFLGITPF
810 820 830 840 850
LNYTRTLRFD EDKGFWCQGL EGGKTRCLGR SKGRRYPDMD MESRLFLTDF
860 870 880
FRNHNLELSK LLSRLGQPAP LWLREELQHS SVG
Length:883
Mass (Da):101,202
Last modified:October 1, 1996 - v1
Checksum:i8AC8C7BEF5B8EED8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti118A → V in CAA53479 (PubMed:8144627).Curated1
Sequence conflicti396Missing in CAA53479 (PubMed:8144627).Curated1
Sequence conflicti461P → L in BAE29307 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02304 mRNA. Translation: AAC52137.1.
X75885 mRNA. Translation: CAA53479.1.
AF074925 mRNA. Translation: AAD15979.1.
AK150100 mRNA. Translation: BAE29307.1.
BC110480 mRNA. Translation: AAI10481.1.
CCDSiCCDS26854.1.
PIRiA49733.
RefSeqiNP_034941.2. NM_010811.2.
UniGeneiMm.4084.

Genome annotation databases

EnsembliENSMUST00000047490; ENSMUSP00000040227; ENSMUSG00000039308.
GeneIDi17423.
KEGGimmu:17423.
UCSCiuc007sks.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02304 mRNA. Translation: AAC52137.1.
X75885 mRNA. Translation: CAA53479.1.
AF074925 mRNA. Translation: AAD15979.1.
AK150100 mRNA. Translation: BAE29307.1.
BC110480 mRNA. Translation: AAI10481.1.
CCDSiCCDS26854.1.
PIRiA49733.
RefSeqiNP_034941.2. NM_010811.2.
UniGeneiMm.4084.

3D structure databases

ProteinModelPortaliP52850.
SMRiP52850.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000040227.

PTM databases

PhosphoSitePlusiP52850.

Proteomic databases

PaxDbiP52850.
PRIDEiP52850.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000047490; ENSMUSP00000040227; ENSMUSG00000039308.
GeneIDi17423.
KEGGimmu:17423.
UCSCiuc007sks.1. mouse.

Organism-specific databases

CTDi8509.
MGIiMGI:97040. Ndst2.

Phylogenomic databases

eggNOGiKOG3703. Eukaryota.
ENOG410XQN4. LUCA.
GeneTreeiENSGT00760000119023.
HOGENOMiHOG000008010.
HOVERGENiHBG082011.
InParanoidiP52850.
KOiK02577.
OMAiDKYLNMD.
OrthoDBiEOG091G02CP.
PhylomeDBiP52850.
TreeFamiTF313193.

Enzyme and pathway databases

UniPathwayiUPA00756.
UPA00862.
BRENDAi2.8.2.8. 3474.
ReactomeiR-MMU-2022928. HS-GAG biosynthesis.

Miscellaneous databases

ChiTaRSiNdst2. mouse.
PROiP52850.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000039308.
GenevisibleiP52850. MM.

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 nameiNDST2_MOUSE
AccessioniPrimary (citable) accession number: P52850
Secondary accession number(s): Q3UDF4, Q549P5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 134 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.