Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 4

Gene

NDST4

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

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 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

Keywordsi

Molecular functionHydrolase, Multifunctional enzyme, Transferase

Enzyme and pathway databases

BioCyciMetaCyc: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

EuPathDBiHostDB:ENSG00000138653.9
HGNCiHGNC:20779 NDST4
MIMi615039 gene
neXtProtiNX_Q9H3R1

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 – 872LumenalSequence analysisAdd BLAST838

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...) asparagineSequence analysis1
Glycosylationi341N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi391N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi657N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi793N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi808 ↔ 818By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9H3R1
PaxDbiQ9H3R1
PeptideAtlasiQ9H3R1
PRIDEiQ9H3R1
ProteomicsDBi80743

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
OMAiVSMDSWN
OrthoDBiEOG091G02CP
PhylomeDBiQ9H3R1
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 (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 dbSNP:rs35181627Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiNDST4_HUMAN
AccessioniPrimary (citable) accession number: Q9H3R1
Secondary accession number(s): Q2KHM8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: March 1, 2001
Last modified: June 20, 2018
This is version 126 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. 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

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health