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Protein

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 4

Gene

NDST4

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 low deacetylase activity but high sulfotransferase activity (By similarity).By similarity

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 sitei604For sulfotransferase activityBy similarity1
Binding sitei702PAPSBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi604 – 608PAPSBy similarity5
Nucleotide bindingi823 – 827PAPSBy similarity5

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Transferase

Enzyme and pathway databases

BioCyciMetaCyc:HS06527-MONOMER.
ZFISH:HS06527-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 4 (EC:2.8.2.8)
Alternative name(s):
Glucosaminyl N-deacetylase/N-sulfotransferase 4
Short name:
NDST-4
N-heparan sulfate sulfotransferase 4
Short name:
N-HSST 4
Including the following 2 domains:
Heparan sulfate N-deacetylase 4 (EC:3.-.-.-)
Heparan sulfate N-sulfotransferase 4 (EC:2.8.2.-)
Gene namesi
Name:NDST4
Synonyms:HSST4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:20779. NDST4.

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 – 872LumenalSequence analysisAdd BLAST838

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi64579.
OpenTargetsiENSG00000138653.
PharmGKBiPA134875549.

Polymorphism and mutation databases

BioMutaiNDST4.
DMDMi74718249.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002256611 – 872Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 4Add BLAST872

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi226N-linked (GlcNAc...)Sequence analysis1
Glycosylationi341N-linked (GlcNAc...)Sequence analysis1
Glycosylationi391N-linked (GlcNAc...)Sequence analysis1
Glycosylationi657N-linked (GlcNAc...)Sequence analysis1
Glycosylationi793N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi808 ↔ 818By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9H3R1.
PaxDbiQ9H3R1.
PeptideAtlasiQ9H3R1.
PRIDEiQ9H3R1.

PTM databases

iPTMnetiQ9H3R1.
PhosphoSitePlusiQ9H3R1.

Expressioni

Gene expression databases

BgeeiENSG00000138653.
CleanExiHS_NDST4.
GenevisibleiQ9H3R1. HS.

Organism-specific databases

HPAiHPA011129.

Interactioni

Subunit structurei

Monomer.By similarity

Protein-protein interaction databases

STRINGi9606.ENSP00000264363.

Structurei

3D structure databases

ProteinModelPortaliQ9H3R1.
SMRiQ9H3R1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni36 – 588Heparan sulfate N-deacetylase 4Add BLAST553
Regioni589 – 872Heparan sulfate N-sulfotransferase 4Add BLAST284

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3703. Eukaryota.
ENOG410XQN4. LUCA.
GeneTreeiENSGT00760000119023.
HOGENOMiHOG000128094.
HOVERGENiHBG082011.
InParanoidiQ9H3R1.
KOiK02579.
OMAiYPPMDQE.
OrthoDBiEOG091G02CP.
PhylomeDBiQ9H3R1.
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H3R1-1) [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
MNLIVKLRRS FRTLIVLLAT FCLVSIVISA YFLYSGYKQE MTLIETTAEA
60 70 80 90 100
ECTDIKILPY RSMELKTVKP IDTSKTDPTV LLFVESQYSQ LGQDIIAILE
110 120 130 140 150
SSRFQYHMVI APGKGDIPPL TDNGKGKYTL VIYENILKYV SMDSWNRELL
160 170 180 190 200
EKYCVEYSVS IIGFHKANEN SLPSTQLKGF PLNLFNNLAL KDCFVNPQSP
210 220 230 240 250
LLHITKAPKV EKGPLPGEDW TIFQYNHSTY QPVLLTELQT EKSLSSLSSK
260 270 280 290 300
TLFATVIQDL GLHDGIQRVL FGNNLNFWLH KLIFIDAISF LSGKRLTLSL
310 320 330 340 350
DRYILVDIDD IFVGKEGTRM NVKDVKALLE TQNLLRTQVA NFTFNLGFSG
360 370 380 390 400
KFYHTGTEEE DEGDDLLLRS VDEFWWFPHM WSHMQPHLFH NESSLVEQMI
410 420 430 440 450
LNKEFALEHG IPINMGYAVA PHHSGVYPVH IQLYAAWKKV WGIQVTSTEE
460 470 480 490 500
YPHLKPARYR KGFIHNSIMV LPRQTCGLFT HTIFYKEYPG GPQELDKSIR
510 520 530 540 550
GGELFLTILL NPISIFMTHL SNYGNDRLGL YTFVNLVNFV QSWTNLKLQT
560 570 580 590 600
LPPVQLAHQY FELFPEQKDP LWQNPCDDKR HKDIWSREKT CDHLPKFLVI
610 620 630 640 650
GPQKTGTTAL YLFLLMHPSI ISNLPSPKTF EEVQFFNGNN YHKGIDWYMD
660 670 680 690 700
FFPTPSNTTS DFLFEKSANY FHSEEAPRRA ASLVPKAKII TILIDPSDRA
710 720 730 740 750
YSWYQHQRSH EDPAALRFNF YEVISTGHWA PSDLKTLQRR CLVPGWYAVH
760 770 780 790 800
IERWLTYFAT SQLLIIDGQQ LRSDPATVMD EVQKFLGVTP RYNYSEALTF
810 820 830 840 850
DPQKGFWCQL LEGGKTKCLG KSKGRKYPPM DPESRTFLSN YYRDHNVELS
860 870
KLLHRLGQPL PSWLRQELQK VR
Length:872
Mass (Da):100,716
Last modified:March 1, 2001 - v1
Checksum:i9C4E2DD1F98EA859
GO
Isoform 2 (identifier: Q9H3R1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-379: Missing.
     706-748: HQRSHEDPAA...RRCLVPGWYA → VGVQWRDLGS...TNDHMKIQLL
     749-872: Missing.

Note: No experimental confirmation available.
Show »
Length:369
Mass (Da):42,852
Checksum:i334248F67AD6A392
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06189012R → Q.Corresponds to variant rs35181627dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0562561 – 379Missing in isoform 2. 1 PublicationAdd BLAST379
Alternative sequenceiVSP_056257706 – 748HQRSH…PGWYA → VGVQWRDLGSLQPSPPRFMP FSCLSLLSSWDYSTNDHMKI QLL in isoform 2. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_056258749 – 872Missing in isoform 2. 1 PublicationAdd BLAST124

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB036429 mRNA. Translation: BAB18535.1.
AC093656 Genomic DNA. No translation available.
AC097519 Genomic DNA. No translation available.
AC109821 Genomic DNA. No translation available.
AC110777 Genomic DNA. No translation available.
BC113075 mRNA. Translation: AAI13076.1.
CCDSiCCDS3706.1. [Q9H3R1-1]
RefSeqiNP_072091.1. NM_022569.2. [Q9H3R1-1]
UniGeneiHs.591700.

Genome annotation databases

EnsembliENST00000264363; ENSP00000264363; ENSG00000138653. [Q9H3R1-1]
ENST00000504854; ENSP00000423218; ENSG00000138653. [Q9H3R1-2]
ENST00000613194; ENSP00000483949; ENSG00000138653. [Q9H3R1-2]
GeneIDi64579.
KEGGihsa:64579.
UCSCiuc003ibu.4. human. [Q9H3R1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB036429 mRNA. Translation: BAB18535.1.
AC093656 Genomic DNA. No translation available.
AC097519 Genomic DNA. No translation available.
AC109821 Genomic DNA. No translation available.
AC110777 Genomic DNA. No translation available.
BC113075 mRNA. Translation: AAI13076.1.
CCDSiCCDS3706.1. [Q9H3R1-1]
RefSeqiNP_072091.1. NM_022569.2. [Q9H3R1-1]
UniGeneiHs.591700.

3D structure databases

ProteinModelPortaliQ9H3R1.
SMRiQ9H3R1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000264363.

PTM databases

iPTMnetiQ9H3R1.
PhosphoSitePlusiQ9H3R1.

Polymorphism and mutation databases

BioMutaiNDST4.
DMDMi74718249.

Proteomic databases

MaxQBiQ9H3R1.
PaxDbiQ9H3R1.
PeptideAtlasiQ9H3R1.
PRIDEiQ9H3R1.

Protocols and materials databases

DNASUi64579.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264363; ENSP00000264363; ENSG00000138653. [Q9H3R1-1]
ENST00000504854; ENSP00000423218; ENSG00000138653. [Q9H3R1-2]
ENST00000613194; ENSP00000483949; ENSG00000138653. [Q9H3R1-2]
GeneIDi64579.
KEGGihsa:64579.
UCSCiuc003ibu.4. human. [Q9H3R1-1]

Organism-specific databases

CTDi64579.
DisGeNETi64579.
GeneCardsiNDST4.
HGNCiHGNC:20779. NDST4.
HPAiHPA011129.
MIMi615039. gene.
neXtProtiNX_Q9H3R1.
OpenTargetsiENSG00000138653.
PharmGKBiPA134875549.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3703. Eukaryota.
ENOG410XQN4. LUCA.
GeneTreeiENSGT00760000119023.
HOGENOMiHOG000128094.
HOVERGENiHBG082011.
InParanoidiQ9H3R1.
KOiK02579.
OMAiYPPMDQE.
OrthoDBiEOG091G02CP.
PhylomeDBiQ9H3R1.
TreeFamiTF313193.

Enzyme and pathway databases

UniPathwayiUPA00756.
UPA00862.
BioCyciMetaCyc:HS06527-MONOMER.
ZFISH:HS06527-MONOMER.
BRENDAi2.8.2.8. 2681.
ReactomeiR-HSA-2022928. HS-GAG biosynthesis.

Miscellaneous databases

ChiTaRSiNDST4. human.
GenomeRNAii64579.
PROiQ9H3R1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138653.
CleanExiHS_NDST4.
GenevisibleiQ9H3R1. 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 nameiNDST4_HUMAN
AccessioniPrimary (citable) accession number: Q9H3R1
Secondary accession number(s): Q2KHM8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: March 1, 2001
Last modified: November 2, 2016
This is version 118 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.