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Protein

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 3

Gene

NDST3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Transferase

Enzyme and pathway databases

BioCyciMetaCyc:HS09011-MONOMER.
ZFISH:HS09011-MONOMER.
BRENDAi2.8.2.8. 2681.
ReactomeiR-HSA-2022928. HS-GAG biosynthesis.
UniPathwayiUPA00756.
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

HGNCiHGNC:7682. NDST3.

Subcellular locationi

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

GO - Cellular componenti

Complete GO annotation...

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...)Sequence analysis1
Glycosylationi226N-linked (GlcNAc...)Sequence analysis1
Glycosylationi342N-linked (GlcNAc...)Sequence analysis1
Glycosylationi392N-linked (GlcNAc...)Sequence analysis1
Glycosylationi658N-linked (GlcNAc...)Sequence analysis1
Glycosylationi794N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi809 ↔ 819By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO95803.
PeptideAtlasiO95803.
PRIDEiO95803.

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.
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

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.

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

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

PaxDbiO95803.
PeptideAtlasiO95803.
PRIDEiO95803.

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.
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

UniPathwayiUPA00756.
UPA00862.
BioCyciMetaCyc:HS09011-MONOMER.
ZFISH:HS09011-MONOMER.
BRENDAi2.8.2.8. 2681.
ReactomeiR-HSA-2022928. HS-GAG biosynthesis.

Miscellaneous databases

ChiTaRSiNDST3. human.
GeneWikiiNDST3.
GenomeRNAii9348.
PROiO95803.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164100.
CleanExiHS_NDST3.
GenevisibleiO95803. HS.

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 nameiNDST3_HUMAN
AccessioniPrimary (citable) accession number: O95803
Secondary accession number(s): B4DI67
, Q4W5C1, Q4W5D0, Q6UWC5, Q9UP21
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: May 1, 1999
Last modified: November 2, 2016
This is version 127 of the entry and version 1 of the sequence. [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

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, Multifunctional enzyme, Reference proteome

Documents

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