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Protein

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 3

Gene

NDST3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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. Has high deacetylase activity but low sulfotransferase activity.1 Publication

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.

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 sitei605For sulfotransferase activityBy similarity1
Binding sitei703PAPSBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi605 – 609PAPSBy similarity5
Nucleotide bindingi824 – 828PAPSBy similarity5

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Multifunctional enzyme, Transferase

Enzyme and pathway databases

BioCyciMetaCyc:HS09011-MONOMER
BRENDAi2.8.2.8 2681
ReactomeiR-HSA-2022928 HS-GAG biosynthesis
UniPathwayi
UPA00756

UPA00862

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 3 (EC:2.8.2.8)
Alternative name(s):
Glucosaminyl N-deacetylase/N-sulfotransferase 3
Short name:
NDST-3
Short name:
hNDST-3
N-heparan sulfate sulfotransferase 3
Short name:
N-HSST 3
Including the following 2 domains:
Heparan sulfate N-deacetylase 3 (EC:3.-.-.-)
Heparan sulfate N-sulfotransferase 3 (EC:2.8.2.-)
Gene namesi
Name:NDST3
Synonyms:HSST3
ORF Names:UNQ2544/PRO4998
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000164100.8
HGNCiHGNC:7682 NDST3
MIMi603950 gene
neXtProtiNX_O95803

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 13CytoplasmicSequence analysisAdd BLAST13
Transmembranei14 – 34Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini35 – 873LumenalSequence analysisAdd BLAST839

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi9348
OpenTargetsiENSG00000164100
PharmGKBiPA31488

Polymorphism and mutation databases

BioMutaiNDST3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002256591 – 873Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 3Add BLAST873

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi146N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi226N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi342N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi392N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi658N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi794N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi809 ↔ 819By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO95803
PaxDbiO95803
PeptideAtlasiO95803
PRIDEiO95803
ProteomicsDBi51059
51060 [O95803-2]

PTM databases

iPTMnetiO95803
PhosphoSitePlusiO95803

Expressioni

Tissue specificityi

Expressed in brain, kidney, liver, fetal and adult lung, adult pancreas, placenta, fetal spleen and fetal thymus. Not detected in adult/ fetal heart and skeletal muscle.1 Publication

Gene expression databases

BgeeiENSG00000164100 Expressed in 79 organ(s), highest expression level in buccal mucosa cell
CleanExiHS_NDST3
GenevisibleiO95803 HS

Organism-specific databases

HPAiHPA056189

Interactioni

Subunit structurei

Monomer.By similarity

Protein-protein interaction databases

STRINGi9606.ENSP00000296499

Structurei

3D structure databases

ProteinModelPortaliO95803
SMRiO95803
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni36 – 589Heparan sulfate N-deacetylase 3Add BLAST554
Regioni590 – 873Heparan sulfate N-sulfotransferase 3Add BLAST284

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3703 Eukaryota
ENOG410XQN4 LUCA
GeneTreeiENSGT00760000119023
HOGENOMiHOG000008010
HOVERGENiHBG082011
InParanoidiO95803
KOiK02578
OMAiTVIHDLG
OrthoDBiEOG091G02CP
PhylomeDBiO95803
TreeFamiTF313193

Family and domain databases

InterProiView protein in InterPro
IPR021930 Heparan_SO4_deacetylase
IPR037359 NST/OST
IPR027417 P-loop_NTPase
IPR000863 Sulfotransferase_dom
PANTHERiPTHR10605 PTHR10605, 1 hit
PfamiView protein in Pfam
PF12062 HSNSD, 1 hit
PF00685 Sulfotransfer_1, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: O95803-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSFIMKLHRH FQRTVILLAT FCMVSIIISA YYLYSGYKQE NELSETASEV
60 70 80 90 100
DCGDLQHLPY QLMEVKAMKL FDASRTDPTV LVFVESQYSS LGQDIIMILE
110 120 130 140 150
SSRFQYHIEI APGKGDLPVL IDKMKGKYIL IIYENILKYI NMDSWNRSLL
160 170 180 190 200
DKYCVEYGVG VIGFHKTSEK SVQSFQLKGF PFSIYGNLAV KDCCINPHSP
210 220 230 240 250
LIRVTKSSKL EKGSLPGTDW TVFQINHSAY QPVIFAKVKT PENLSPSISK
260 270 280 290 300
GAFYATIIHD LGLHDGIQRV LFGNNLNFWL HKLIFIDAIS FLSGKRLTLS
310 320 330 340 350
LDRYILVDID DIFVGKEGTR MNTNDVKALL DTQNLLRAQI TNFTFNLGFS
360 370 380 390 400
GKFYHTGTEE EDEGDDCLLG SVDEFWWFPH MWSHMQPHLF HNESSLVEQM
410 420 430 440 450
ILNKKFALEH GIPTDMGYAV APHHSGVYPV HVQLYEAWKK VWNIKITSTE
460 470 480 490 500
EYPHLKPARY RRGFIHKNIM VLPRQTCGLF THTIFYKEYP GGPKELDKSI
510 520 530 540 550
QGGELFFTVV LNPISIFMTH LSNYGNDRLG LYTFVNLANF VKSWTNLRLQ
560 570 580 590 600
TLPPVQLAHK YFELFPDQKD PLWQNPCDDK RHRDIWSKEK TCDRLPKFLV
610 620 630 640 650
IGPQKTGTTA LYLFLVMHPS ILSNSPSPKT FEEVQFFNRN NYHRGIDWYM
660 670 680 690 700
DFFPVPSNVT TDFLFEKSAN YFHSEEAPKR AASLVPKAKI ITILIDPSDR
710 720 730 740 750
AYSWYQHQRS HEDPAALKFS FYEVISAGPR APSELRALQK RCLVPGWYAS
760 770 780 790 800
HIERWLVYFP PFQLLIIDGQ QLRTDPATVM DEVQKFLGVL PHYNYSEALT
810 820 830 840 850
FDSHKGFWCQ LLEEGKTKCL GKSKGRKYPP MDSDSRTFLS SYYRDHNVEL
860 870
SKLLHKLGQP LPSWLRQELQ KVR
Length:873
Mass (Da):100,902
Last modified:May 1, 1999 - v1
Checksum:i4DDE39257CAC0D36
GO
Isoform 2 (identifier: O95803-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     328-385: ALLDTQNLLR...WWFPHMWSHM → VRLYFLKFQS...NQLRRLCISI
     386-873: Missing.

Note: No experimental confirmation available.
Show »
Length:385
Mass (Da):43,766
Checksum:i55EAC286AA742C09
GO
Isoform 3 (identifier: O95803-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     328-408: Missing.
     635-642: QFFNRNNY → YGFLPSPI
     643-873: Missing.

Note: No experimental confirmation available.
Show »
Length:561
Mass (Da):64,297
Checksum:i644886B36ADFA6FA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8 – 17HRHFQRTVIL → STEQLSKEPVISW in AAD46061 (Ref. 2) Curated10

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036131264H → Q in a colorectal cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_054350328 – 408Missing in isoform 3. 1 PublicationAdd BLAST81
Alternative sequenceiVSP_017405328 – 385ALLDT…MWSHM → VRLYFLKFQSSVHLPAGIQL SQFVLQLGYPGHGIYWESLG NLGLSLTLNQLRRLCISI in isoform 2. 1 PublicationAdd BLAST58
Alternative sequenceiVSP_017406386 – 873Missing in isoform 2. 1 PublicationAdd BLAST488
Alternative sequenceiVSP_054351635 – 642QFFNRNNY → YGFLPSPI in isoform 3. 1 Publication8
Alternative sequenceiVSP_054352643 – 873Missing in isoform 3. 1 PublicationAdd BLAST231

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF074924 mRNA Translation: AAD15978.1
AF076605 mRNA Translation: AAD46061.1
AY358852 mRNA Translation: AAQ89211.1
AK295439 mRNA Translation: BAG58379.1
AC096762 Genomic DNA No translation available.
AC108201 Genomic DNA Translation: AAY41001.1
AC110999 Genomic DNA Translation: AAY41056.1
AC116639 Genomic DNA No translation available.
BC109309 mRNA Translation: AAI09310.1
BC109310 mRNA Translation: AAI09311.1
CCDSiCCDS3708.1 [O95803-1]
RefSeqiNP_004775.1, NM_004784.2 [O95803-1]
XP_006714479.1, XM_006714416.3 [O95803-1]
UniGeneiHs.480596

Genome annotation databases

EnsembliENST00000296499; ENSP00000296499; ENSG00000164100 [O95803-1]
GeneIDi9348
KEGGihsa:9348
UCSCiuc003ibx.4 human [O95803-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF074924 mRNA Translation: AAD15978.1
AF076605 mRNA Translation: AAD46061.1
AY358852 mRNA Translation: AAQ89211.1
AK295439 mRNA Translation: BAG58379.1
AC096762 Genomic DNA No translation available.
AC108201 Genomic DNA Translation: AAY41001.1
AC110999 Genomic DNA Translation: AAY41056.1
AC116639 Genomic DNA No translation available.
BC109309 mRNA Translation: AAI09310.1
BC109310 mRNA Translation: AAI09311.1
CCDSiCCDS3708.1 [O95803-1]
RefSeqiNP_004775.1, NM_004784.2 [O95803-1]
XP_006714479.1, XM_006714416.3 [O95803-1]
UniGeneiHs.480596

3D structure databases

ProteinModelPortaliO95803
SMRiO95803
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000296499

PTM databases

iPTMnetiO95803
PhosphoSitePlusiO95803

Polymorphism and mutation databases

BioMutaiNDST3

Proteomic databases

EPDiO95803
PaxDbiO95803
PeptideAtlasiO95803
PRIDEiO95803
ProteomicsDBi51059
51060 [O95803-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296499; ENSP00000296499; ENSG00000164100 [O95803-1]
GeneIDi9348
KEGGihsa:9348
UCSCiuc003ibx.4 human [O95803-1]

Organism-specific databases

CTDi9348
DisGeNETi9348
EuPathDBiHostDB:ENSG00000164100.8
GeneCardsiNDST3
HGNCiHGNC:7682 NDST3
HPAiHPA056189
MIMi603950 gene
neXtProtiNX_O95803
OpenTargetsiENSG00000164100
PharmGKBiPA31488
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3703 Eukaryota
ENOG410XQN4 LUCA
GeneTreeiENSGT00760000119023
HOGENOMiHOG000008010
HOVERGENiHBG082011
InParanoidiO95803
KOiK02578
OMAiTVIHDLG
OrthoDBiEOG091G02CP
PhylomeDBiO95803
TreeFamiTF313193

Enzyme and pathway databases

UniPathwayi
UPA00756

UPA00862

BioCyciMetaCyc:HS09011-MONOMER
BRENDAi2.8.2.8 2681
ReactomeiR-HSA-2022928 HS-GAG biosynthesis

Miscellaneous databases

ChiTaRSiNDST3 human
GeneWikiiNDST3
GenomeRNAii9348
PROiPR:O95803
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164100 Expressed in 79 organ(s), highest expression level in buccal mucosa cell
CleanExiHS_NDST3
GenevisibleiO95803 HS

Family and domain databases

InterProiView protein in InterPro
IPR021930 Heparan_SO4_deacetylase
IPR037359 NST/OST
IPR027417 P-loop_NTPase
IPR000863 Sulfotransferase_dom
PANTHERiPTHR10605 PTHR10605, 1 hit
PfamiView protein in Pfam
PF12062 HSNSD, 1 hit
PF00685 Sulfotransfer_1, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNDST3_HUMAN
AccessioniPrimary (citable) accession number: O95803
Secondary accession number(s): B4DI67
, Q4W5C1, Q4W5D0, Q6UWC5, Q9UP21
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: May 1, 1999
Last modified: September 12, 2018
This is version 137 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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