Reviewed, UniProtKB/Swiss-Prot P52848 (NDST1_HUMAN)

Names and origin

Protein names

Recommended name:
    Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1
    EC=2.8.2.8
Alternative name(s):
    Glucosaminyl N-deacetylase/N-sulfotransferase 1
      Short name=NDST-1
    [Heparan sulfate]-glucosamine N-sulfotransferase 1
      Short name=HSNST 1
    N-heparan sulfate sulfotransferase 1
      Short name=N-HSST 1
Including the following 2 domains:
    1- Recommended name:
            Heparan sulfate N-deacetylase 1
              EC=3.-.-.-
    2- Recommended name:
            Heparan sulfate N-sulfotransferase 1
              EC=2.8.2.-

Gene names

Name:	NDST1
Synonyms:	HSST, HSST1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	882 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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 dissacharide 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. Compared to other NDST enzymes, its presence is absolutely required. Participates in biosynthesis of heparan sulfate that can ultimately serve as L-selectin ligands, thereby playing a role in inflammatory response. Ref.6 Ref.7
Catalytic activity	3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine = adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine.
Pathway	Glycan metabolism; heparan sulfate biosynthesis. Glycan metabolism; heparin biosynthesis.
Subunit structure	Monomer.
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein. Ref.2
Tissue specificity	Widely expressed. Expression is most abundant in heart, liver and pancreas.
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.
Sequence similarities	Belongs to the sulfotransferase 1 family. NDST subfamily.
Biophysicochemical properties	Kinetic parameters: KM=13.3 µM for K5 polysaccharide KM=0.35 µM for N-acetylated HS-II

Ontologies

Keywords
Biological process	Inflammatory response
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal-anchor Transmembrane
Molecular function	Hydrolase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	heparan sulfate proteoglycan biosynthetic process Traceable author statement. Source: ProtInc inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	[heparan sulfate]-glucosamine N-sulfotransferase activity Inferred from electronic annotation. Source: EC hydrolase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P52848-1)

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.

Isoform 2 (identifier: P52848-2)

The sequence of this isoform differs from the canonical sequence as follows:
     523-556: ISIFMTHLSNYGNDRLGLYTFKHLVRFLHSWTNL → VSAPQPMAAGEKGLLHSLSAADTGFLEPGKGGEA
     557-882: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 882

882

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1

PRO_0000085210

Regions

Topological domain

1 – 17

17

Cytoplasmic Potential

Transmembrane

18 – 39

22

Signal-anchor for type II membrane protein Potential

Topological domain

40 – 882

843

Lumenal Potential

Nucleotide binding

614 – 618

5

PAPS

Nucleotide binding

833 – 837

5

PAPS

Region

40 – 598

559

Heparan sulfate N-deacetylase 1

Region

599 – 882

284

Heparan sulfate N-sulfotransferase 1

Sites

Active site

614

1

For sulfotransferase activity

Binding site

712

1

PAPS

Amino acid modifications

Glycosylation

231

1

N-linked (GlcNAc...) Potential

Glycosylation

351

1

N-linked (GlcNAc...) Potential

Glycosylation

401

1

N-linked (GlcNAc...) Potential

Glycosylation

667

1

N-linked (GlcNAc...) Potential

Disulfide bond

818 ↔ 828

Ref.8

Natural variations

Alternative sequence

523 – 556

34

ISIFM…SWTNL → VSAPQPMAAGEKGLLHSLSA ADTGFLEPGKGGEA in isoform 2.

VSP_017397

Alternative sequence

557 – 882

326

Missing in isoform 2.

VSP_017398

Experimental info

Mutagenesis

614

1

K → A: Loss of sulfotransferase activity. Ref.5

Sequence conflict

24 – 28

5

FIFCL → QVVCQ in AAH12888. Ref.4

Sequence conflict

60

1

P → A in AAA67765. Ref.3

Sequence conflict

364

1

H → Q in AAH12888. Ref.4

Sequence conflict

689

1

R → G in AAA67765. Ref.3

Sequence conflict

743

1

K → R in AAA67765. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

882

Helix Strand Turn

Details...

Beta strand

604 – 609

6

Helix

617 – 625

9

Beta strand

630 – 632

3

Turn

637 – 639

3

Beta strand

646 – 648

3

Helix

649 – 653

5

Helix

655 – 659

5

Beta strand

672 – 676

5

Helix

679 – 682

4

Helix

686 – 693

8

Beta strand

698 – 703

6

Helix

706 – 719

14

Helix

723 – 727

5

Helix

730 – 734

5

Helix

742 – 752

11

Helix

753 – 755

3

Helix

757 – 765

9

Helix

770 – 772

3

Beta strand

773 – 777

5

Helix

778 – 783

6

Helix

785 – 796

12

Helix

805 – 807

3

Beta strand

808 – 811

4

Turn

812 – 815

4

Beta strand

816 – 820

5

Helix

842 – 866

25

Helix

872 – 878

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: D4B716B84A0BF4C4	FASTA	882	100,868
	10 20 30 40 50 60 MPALACLRRL CRHVSPQAVL FLLFIFCLFS VFISAYYLYG WKRGLEPSAD APEPDCGDPP 70 80 90 100 110 120 PVAPSRLLPL KPVQAATPSR TDPLVLVFVE SLYSQLGQEV VAILESSRFK YRTEIAPGKG 130 140 150 160 170 180 DMPTLTDKGR GRFALIIYEN ILKYVNLDAW NRELLDKYCV AYGVGIIGFF KANENSLLSA 190 200 210 220 230 240 QLKGFPLFLH SNLGLKDCSI NPKSPLLYVT RPSEVEKGVL PGEDWTVFQS NHSTYEPVLL 250 260 270 280 290 300 AKTRSSESIP HLGADAGLHA ALHATVVQDL GLHDGIQRVL FGNNLNFWLH KLVFVDAVAF 310 320 330 340 350 360 LTGKRLSLPL DRYILVDIDD IFVGKEGTRM KVEDVKALFD TQNELRAHIP NFTFNLGYSG 370 380 390 400 410 420 KFFHTGTNAE DAGDDLLLSY VKEFWWFPHM WSHMQPHLFH NQSVLAEQMA LNKKFAVEHG 430 440 450 460 470 480 IPTDMGYAVA PHHSGVYPVH VQLYEAWKQV WSIRVTSTEE YPHLKPARYR RGFIHNGIMV 490 500 510 520 530 540 LPRQTCGLFT HTIFYNEYPG GSSELDKIIN GGELFLTVLL NPISIFMTHL SNYGNDRLGL 550 560 570 580 590 600 YTFKHLVRFL HSWTNLRLQT LPPVQLAQKY FQIFSEEKDP LWQDPCEDKR HKDIWSKEKT 610 620 630 640 650 660 CDRFPKLLII GPQKTGTTAL YLFLGMHPDL SSNYPSSETF EEIQFFNGHN YHKGIDWYME 670 680 690 700 710 720 FFPIPSNTTS DFYFEKSANY FDSEVAPRRA AALLPKAKVL TILINPADRA YSWYQHQRAH 730 740 750 760 770 780 DDPVALKYTF HEVITAGSDA SSKLRALQNR CLVPGWYATH IERWLSAYHA NQILVLDGKL 790 800 810 820 830 840 LRTEPAKVMD MVQKFLGVTN TIDYHKTLAF DPKKGFWCQL LEGGKTKCLG KSKGRKYPEM 850 860 870 880 DLDSRAFLKD YYRDHNIELS KLLYKMGQTL PTWLREDLQN TR
	Isoform 2. Checksum: C3D09802532B4D97	FASTA	556	62,065
	10 20 30 40 50 60 MPALACLRRL CRHVSPQAVL FLLFIFCLFS VFISAYYLYG WKRGLEPSAD APEPDCGDPP 70 80 90 100 110 120 PVAPSRLLPL KPVQAATPSR TDPLVLVFVE SLYSQLGQEV VAILESSRFK YRTEIAPGKG 130 140 150 160 170 180 DMPTLTDKGR GRFALIIYEN ILKYVNLDAW NRELLDKYCV AYGVGIIGFF KANENSLLSA 190 200 210 220 230 240 QLKGFPLFLH SNLGLKDCSI NPKSPLLYVT RPSEVEKGVL PGEDWTVFQS NHSTYEPVLL 250 260 270 280 290 300 AKTRSSESIP HLGADAGLHA ALHATVVQDL GLHDGIQRVL FGNNLNFWLH KLVFVDAVAF 310 320 330 340 350 360 LTGKRLSLPL DRYILVDIDD IFVGKEGTRM KVEDVKALFD TQNELRAHIP NFTFNLGYSG 370 380 390 400 410 420 KFFHTGTNAE DAGDDLLLSY VKEFWWFPHM WSHMQPHLFH NQSVLAEQMA LNKKFAVEHG 430 440 450 460 470 480 IPTDMGYAVA PHHSGVYPVH VQLYEAWKQV WSIRVTSTEE YPHLKPARYR RGFIHNGIMV 490 500 510 520 530 540 LPRQTCGLFT HTIFYNEYPG GSSELDKIIN GGELFLTVLL NPVSAPQPMA AGEKGLLHSL 550 SAADTGFLEP GKGGEA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the human heparan sulfate-N-deacetylase/N-sulfotransferase gene from the Treacher Collins syndrome candidate region at 5q32-q33.1." Dixon J., Loftus S.K., Gladwin A.J., Scambler P.J., Wasmuth J.J., Dixon M.J. Genomics 26:239-244(1995) [PubMed: 7601448] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[2]	"Localization of human heparan glucosaminyl N-deacetylase/N-sulphotransferase to the trans-Golgi network." Humphries D.E., Sullivan B.M., Aleixo M.D., Stow J.L. Biochem. J. 325:351-357(1997) [PubMed: 9230113] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION. Tissue: Umbilical vein endothelial cell.
[3]	Labell T.L., Milewicz D.J., Bonadio J., Edelhoff S., Disteche C.M., Byers P.H. Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fibroblast.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Lung.
[5]	"A role of Lys614 in the sulfotransferase activity of human heparan sulfate N-deacetylase/N-sulfotransferase." Sueyoshi T., Kakuta Y., Pedersen L.C., Wall F.E., Pedersen L.G., Negishi M. FEBS Lett. 433:211-214(1998) [PubMed: 9744796] [Abstract] Cited for: MUTAGENESIS OF LYS-614.
[6]	"Overexpression of different isoforms of glucosaminyl N-deacetylase/N-sulfotransferase results in distinct heparan sulfate N-sulfation patterns." Pikas D.S., Eriksson I., Kjellen L. Biochemistry 39:4552-4558(2000) [PubMed: 10758005] [Abstract] Cited for: FUNCTION.
[7]	"Antibody-based assay for N-deacetylase activity of heparan sulfate/heparin N-deacetylase/N-sulfotransferase (NDST): novel characteristics of NDST-1 and -2." van den Born J., Pikas D.S., Pisa B.J., Eriksson I., Kjellen L., Berden J.H.M. Glycobiology 13:1-10(2003) [PubMed: 12634318] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[8]	"Crystal structure of the sulfotransferase domain of human heparan sulfate N-deacetylase/N-sulfotransferase 1." Kakuta Y., Sueyoshi T., Negishi M., Pedersen L.C. J. Biol. Chem. 274:10673-10676(1999) [PubMed: 10196134] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 579-882 IN COMPLEX WITH PAP, DISULFIDE BOND.
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Cross-references

Sequence databases

EMBLGenBankDDBJ

U18918 mRNA. Translation: AAA75281.1.
U36600 mRNA. Translation: AAC27354.1.
U17970 mRNA. Translation: AAA67765.1.
BC012888 mRNA. Translation: AAH12888.1.

IPI

IPI00738468.
IPI00784368.

PIR

A57169.

RefSeq

NP_001534.1.

UniGene

Hs.222055

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NST	X-ray	2.30	A	558-882	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P52848.

PTM databases

PhosphoSite

P52848.

Proteomic databases

PRIDE

P52848.

Genome annotation databases

Ensembl

ENST00000261797; ENSP00000261797; ENSG00000070614; Homo sapiens. [Genome view]
ENST00000424060; ENSP00000414827; ENSG00000070614; Homo sapiens. [Genome view]

GeneID

3340.

KEGG

hsa:3340.

UCSC

uc003lsk.2. human.
uc003lsl.2. human.

Organism-specific databases

CTD

3340.

GeneCards

GC05P149881.

H-InvDB

HIX0005316.

HGNC

HGNC:7680. NDST1.

MIM

600853. gene.

PharmGKB

PA31486.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P52848.

OMA

KMGQTLP.

Enzyme and pathway databases

BRENDA

2.8.2.8. 247.

Gene expression databases

ArrayExpress

P52848.

Bgee

P52848.

CleanEx

HS_NDST1.

Genevestigator

P52848.

Family and domain databases

InterPro

IPR000863. Sulfotransferase.
[Graphical view]

Pfam

PF00685. Sulfotransfer_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

13220.

SOURCE

Search...

Entry information

Entry name

NDST1_HUMAN

Accession

Primary (citable) accession number: P52848
Secondary accession number(s): Q96E57

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 3, 2009
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.