Reviewed, UniProtKB/Swiss-Prot Q3UHN9 (NDST1_MOUSE)

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

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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.2 Ref.4 Ref.5 Ref.7 Ref.8 Ref.9
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 By similarity.
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein By similarity.
Tissue specificity	Widely expressed in adult and throughout development. Ref.2
Disruption phenotype	Mice survive until birth but are cyanotic and die neonatally in a condition resembling respiratory distress syndrome. In addition, a minor proportion of mice embryos die during the embryonic period. Mutant mice display cerebral hypoplasia and craniofacial defects, disturbed Ca2+ kinetics in myotubes. They also display deficiencies L-selectin and chemokine-mediated neutrophil trafficking during inflammatory responses. Ref.4 Ref.5 Ref.7 Ref.8
Miscellaneous	The presence of 4 different NDST 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.
Sequence caution	The sequence BAE41527.1 differs from that shown. Reason: Frameshift at position 185.

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	Multifunctional enzyme
Gene Ontology (GO)
Biological process	MAPKKK cascade Ref.8 Inferred from mutant phenotype. Source: MGI embryonic neurocranium morphogenesis Ref.8 Inferred from mutant phenotype. Source: MGI embryonic viscerocranium morphogenesis Ref.8 Inferred from mutant phenotype. Source: MGI fibroblast growth factor receptor signaling pathway Ref.8 Inferred from mutant phenotype. Source: MGI forebrain development Ref.8 Inferred from genetic interaction. Source: MGI glycosaminoglycan metabolic process Ref.8 Inferred from mutant phenotype. Source: MGI inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW midbrain development Ref.8 Inferred from genetic interaction. Source: MGI polysaccharide biosynthetic process Ref.5 Inferred from mutant phenotype. Source: MGI protein amino acid deacetylation Ref.4 Ref.5 Traceable author statement. Source: MGI protein amino acid sulfation Ref.4 Ref.5 Inferred from mutant phenotype. Source: MGI respiratory gaseous exchange Ref.4 Ref.5 Inferred from mutant phenotype. Source: MGI smoothened signaling pathway Ref.8 Inferred from genetic interaction. Source: MGI
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	[heparan sulfate]-glucosamine N-sulfotransferase activity Ref.4 Ref.5 Traceable author statement. Source: MGI hydrolase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q3UHN9-1)

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: Q3UHN9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     480-495: VLPRQTCGLFTHTIFY → RLGDTEVKNPDKSLTS
     496-882: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q3UHN9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     143-185: KYVNLDAWNR...SLLSAQLKGF → SISCHSSSVL...EGFEPGPARV
     186-882: 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_0000225655
Regions
	Topological domain	1 – 17	17	Cytoplasmic Potential
	Transmembrane	18 – 38	21	Signal-anchor for type II membrane protein Potential
	Topological domain	39 – 882	844	Lumenal Potential
	Nucleotide binding	614 – 618	5	PAPS By similarity
	Nucleotide binding	833 – 837	5	PAPS By similarity
	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 By similarity
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		By similarity
Natural variations
	Alternative sequence	143 – 185	43	KYVNL…QLKGF → SISCHSSSVLQTVKGKSAAG PFAQPGRKTGHVPEGFEPGP ARV in isoform 3.		VSP_017399
	Alternative sequence	186 – 882	697	Missing in isoform 3.		VSP_017400
	Alternative sequence	480 – 495	16	VLPRQ…HTIFY → RLGDTEVKNPDKSLTS in isoform 2.		VSP_017401
	Alternative sequence	496 – 882	387	Missing in isoform 2.		VSP_017402
Experimental info
	Mutagenesis	486	1	C → W: Loss of deacetylase activity but does not affect sulfotransferase activity. Ref.6
	Mutagenesis	614	1	K → A: Loss of sulfotransferase activity but does not affect deacetylase activity. Ref.6
	Sequence conflict	109	1	F → S in BAE27818. Ref.3
	Sequence conflict	789	1	M → V in AAC17228. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 7, 2006. Version 2. Checksum: 8BE300ABCB8E648D	FASTA	882	100,726
	10 20 30 40 50 60 MPALACLRRL CRHLSPQAVL FLLFVFCLFS VFVSAYYLYG WNRGLEPSAD ASESDCGDPP 70 80 90 100 110 120 PVAPSRLLPI KPVQAVAPSR 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 TQNELRTHIP NFTFNLGYSG 370 380 390 400 410 420 KFFHTGTDAE DAGDDLLLSY VKEFWWFPHM WSHMQPHLFH NQSVLAEQMA LNKKFAVEHG 430 440 450 460 470 480 IPTDMGYAVA PHHSGVYPVH VQLYEAWKQV WGIRVTSTEE 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 AALLPKAKIL SILINPADRA YSWYQHQRAH 730 740 750 760 770 780 DDPVALKYTF HEVITAGPDA SSKLRALQNR CLVPGWYATH IERWLSAFHA NQILVLDGKL 790 800 810 820 830 840 LRTEPAKVMD TVQKFLGVTS TVDYHKTLAF DPKKGFWCQL LEGGKTKCLG KSKGRKYPEM 850 860 870 880 DLDSRAFLKD YFRDHNIELS KLLYKMGQTL PTWLREDLQN TR
	Isoform 2. Checksum: 7023F8CAA85F2344	FASTA	495	55,731
	10 20 30 40 50 60 MPALACLRRL CRHLSPQAVL FLLFVFCLFS VFVSAYYLYG WNRGLEPSAD ASESDCGDPP 70 80 90 100 110 120 PVAPSRLLPI KPVQAVAPSR 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 TQNELRTHIP NFTFNLGYSG 370 380 390 400 410 420 KFFHTGTDAE DAGDDLLLSY VKEFWWFPHM WSHMQPHLFH NQSVLAEQMA LNKKFAVEHG 430 440 450 460 470 480 IPTDMGYAVA PHHSGVYPVH VQLYEAWKQV WGIRVTSTEE YPHLKPARYR RGFIHNGIMR 490 LGDTEVKNPD KSLTS
	Isoform 3. Checksum: 4877F728103F7FCB	FASTA	185	20,078
	10 20 30 40 50 60 MPALACLRRL CRHLSPQAVL FLLFVFCLFS VFVSAYYLYG WNRGLEPSAD ASESDCGDPP 70 80 90 100 110 120 PVAPSRLLPI KPVQAVAPSR TDPLVLVFVE SLYSQLGQEV VAILESSRFK YRTEIAPGKG 130 140 150 160 170 180 DMPTLTDKGR GRFALIIYEN ILSISCHSSS VLQTVKGKSA AGPFAQPGRK TGHVPEGFEP GPARV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and expression in mouse of two heparan sulfate glucosaminyl N-deacetylase/N-sulfotransferase genes." Kusche-Gullberg M., Eriksson I., Pikas D.S., Kjellen L. J. Biol. Chem. 273:11902-11907(1998) [PubMed: 9565617] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: Leaden X A1. Tissue: Liver.
[2]	"Multiple isozymes of heparan sulfate/heparin GlcNAc N-deacetylase/GlcN N-sulfotransferase. Structure and activity of the fourth member, NDST4." Aikawa J., Grobe K., Tsujimoto M., Esko J.D. J. Biol. Chem. 276:5876-5882(2001) [PubMed: 11087757] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY. Strain: BALB/c. Tissue: Lung.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). Strain: C57BL/6J and NOD. Tissue: Urinary bladder.
[4]	"Targeted disruption of NDST-1 gene leads to pulmonary hypoplasia and neonatal respiratory distress in mice." Fan G., Xiao L., Cheng L., Wang X., Sun B., Hu G. FEBS Lett. 467:7-11(2000) [PubMed: 10664446] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[5]	"Defective heparan sulfate biosynthesis and neonatal lethality in mice lacking N-deacetylase/N-sulfotransferase-1." Ringvall M., Ledin J., Holmborn K., van Kuppevelt T., Ellin F., Eriksson I., Olofsson A.M., Kjellen L., Forsberg E. J. Biol. Chem. 275:25926-25930(2000) [PubMed: 10852901] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]	"Distinct effects on heparan sulfate structure by different active site mutations in NDST-1." Bengtsson J., Eriksson I., Kjellen L. Biochemistry 42:2110-2115(2003) [PubMed: 12590599] [Abstract] Cited for: MUTAGENESIS OF CYS-486 AND LYS-614.
[7]	"Disturbed Ca2+ kinetics in N-deacetylase/N-sulfotransferase-1 defective myotubes." Jenniskens G.J., Ringvall M., Koopman W.J., Ledin J., Kjellen L., Willems P.H.G.M., Forsberg E., Veerkamp J.H., van Kuppevelt T.H. J. Cell Sci. 116:2187-2193(2003) [PubMed: 12692154] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[8]	"Cerebral hypoplasia and craniofacial defects in mice lacking heparan sulfate Ndst1 gene function." Grobe K., Inatani M., Pallerla S.R., Castagnola J., Yamaguchi Y., Esko J.D. Development 132:3777-3786(2005) [PubMed: 16020517] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[9]	"Endothelial heparan sulfate deficiency impairs L-selectin- and chemokine-mediated neutrophil trafficking during inflammatory responses." Wang L., Fuster M., Sriramarao P., Esko J.D. Nat. Immunol. 6:902-910(2005) [PubMed: 16056228] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF049894 mRNA. Translation: AAC17228.1. AF074926 mRNA. Translation: AAD15980.1. AK035642 mRNA. Translation: BAC29136.1. AK147282 mRNA. Translation: BAE27818.1. AK170041 mRNA. Translation: BAE41527.1. Frameshift. AK171013 mRNA. Translation: BAE42184.1. BC066098 mRNA. Translation: AAH66098.1. BC079561 mRNA. Translation: AAH79561.1.
IPI	IPI00404189. IPI00742324. IPI00742333.
RefSeq	NP_032332.2.
UniGene	Mm.181862
3D structure databases
HSSP	HSSP built from PDB template 1NST based on UniProtKB P52848.
SMR	Q3UHN9. Positions 592-879.
ModBase	Search...
PTM databases
PhosphoSite	Q3UHN9.
Genome annotation databases
Ensembl	ENSMUSG00000054008. Mus musculus. [Contig view]
GeneID	15531.
KEGG	mmu:15531.
Organism-specific databases
MGI	MGI:104719. Ndst1.
Phylogenomic databases
HOGENOM	Q3UHN9.
HOVERGEN	Q3UHN9.
OMA	Q3UHN9. KMGQTLP.
Enzyme and pathway databases
BRENDA	2.8.2.8. 244.
Gene expression databases
ArrayExpress	Q3UHN9.
Bgee	Q3UHN9.
GermOnline	ENSMUSG00000054008. Mus musculus.
Family and domain databases
InterPro	IPR000863. Sulfotransferase. [Graphical view]
Pfam	PF00685. Sulfotransfer_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	288464.
SOURCE	Search...

Entry information

Entry name

NDST1_MOUSE

Accession

Primary (citable) accession number: Q3UHN9
Secondary accession number(s): O70353 , Q3TBX3, Q3TDS3, Q8BZE5, Q9R206

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 7, 2006
Last sequence update:	March 7, 2006
Last modified:	June 16, 2009
This is version 39 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)