O95803 (NDST3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Heparan sulfate N-deacetylase 3
   EC=3.-.-.-
2. Heparan sulfate N-sulfotransferase 3
   EC=2.8.2.-

Gene names

Name:	NDST3
Synonyms:	HSST3
ORF Names:	UNQ2544/PRO4998

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	873 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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 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. Ref.1
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	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. Ref.1
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.

Ontologies

Keywords
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Hydrolase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	heparan sulfate proteoglycan biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway heparin biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
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 Inferred from electronic annotation. Source: EC deacetylase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: O95803-1)

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: O95803-2)

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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 873	873	Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 3		PRO_0000225659
Regions
	Topological domain	1 – 13	13	Cytoplasmic Potential
	Transmembrane	14 – 34	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	35 – 873	839	Lumenal Potential
	Nucleotide binding	605 – 609	5	PAPS By similarity
	Nucleotide binding	824 – 828	5	PAPS By similarity
	Region	36 – 589	554	Heparan sulfate N-deacetylase 3
	Region	590 – 873	284	Heparan sulfate N-sulfotransferase 3
Sites
	Active site	605	1	For sulfotransferase activity By similarity
	Binding site	703	1	PAPS By similarity
Amino acid modifications
	Glycosylation	146	1	N-linked (GlcNAc...) Potential
	Glycosylation	226	1	N-linked (GlcNAc...) Potential
	Glycosylation	342	1	N-linked (GlcNAc...) Potential
	Glycosylation	392	1	N-linked (GlcNAc...) Potential
	Glycosylation	658	1	N-linked (GlcNAc...) Potential
	Glycosylation	794	1	N-linked (GlcNAc...) Potential
	Disulfide bond	809 ↔ 819		By similarity
Natural variations
	Alternative sequence	328 – 385	58	ALLDT…MWSHM → VRLYFLKFQSSVHLPAGIQL SQFVLQLGYPGHGIYWESLG NLGLSLTLNQLRRLCISI in isoform 2.		VSP_017405
	Alternative sequence	386 – 873	488	Missing in isoform 2.		VSP_017406
	Natural variant	264	1	H → Q in a colorectal cancer sample; somatic mutation. Ref.6		VAR_036131
Experimental info
	Sequence conflict	8 – 17	10	HRHFQRTVIL → STEQLSKEPVISW in AAD46061. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 4DDE39257CAC0D36	FASTA	873	100,902
	10 20 30 40 50 60 MSFIMKLHRH FQRTVILLAT FCMVSIIISA YYLYSGYKQE NELSETASEV DCGDLQHLPY 70 80 90 100 110 120 QLMEVKAMKL FDASRTDPTV LVFVESQYSS LGQDIIMILE SSRFQYHIEI APGKGDLPVL 130 140 150 160 170 180 IDKMKGKYIL IIYENILKYI NMDSWNRSLL DKYCVEYGVG VIGFHKTSEK SVQSFQLKGF 190 200 210 220 230 240 PFSIYGNLAV KDCCINPHSP LIRVTKSSKL EKGSLPGTDW TVFQINHSAY QPVIFAKVKT 250 260 270 280 290 300 PENLSPSISK GAFYATIIHD LGLHDGIQRV LFGNNLNFWL HKLIFIDAIS FLSGKRLTLS 310 320 330 340 350 360 LDRYILVDID DIFVGKEGTR MNTNDVKALL DTQNLLRAQI TNFTFNLGFS GKFYHTGTEE 370 380 390 400 410 420 EDEGDDCLLG SVDEFWWFPH MWSHMQPHLF HNESSLVEQM ILNKKFALEH GIPTDMGYAV 430 440 450 460 470 480 APHHSGVYPV HVQLYEAWKK VWNIKITSTE EYPHLKPARY RRGFIHKNIM VLPRQTCGLF 490 500 510 520 530 540 THTIFYKEYP GGPKELDKSI QGGELFFTVV LNPISIFMTH LSNYGNDRLG LYTFVNLANF 550 560 570 580 590 600 VKSWTNLRLQ TLPPVQLAHK YFELFPDQKD PLWQNPCDDK RHRDIWSKEK TCDRLPKFLV 610 620 630 640 650 660 IGPQKTGTTA LYLFLVMHPS ILSNSPSPKT FEEVQFFNRN NYHRGIDWYM DFFPVPSNVT 670 680 690 700 710 720 TDFLFEKSAN YFHSEEAPKR AASLVPKAKI ITILIDPSDR AYSWYQHQRS HEDPAALKFS 730 740 750 760 770 780 FYEVISAGPR APSELRALQK RCLVPGWYAS HIERWLVYFP PFQLLIIDGQ QLRTDPATVM 790 800 810 820 830 840 DEVQKFLGVL PHYNYSEALT FDSHKGFWCQ LLEEGKTKCL GKSKGRKYPP MDSDSRTFLS 850 860 870 SYYRDHNVEL SKLLHKLGQP LPSWLRQELQ KVR
	Isoform 2 [UniParc]. Checksum: 55EAC286AA742C09	FASTA	385	43,766
	10 20 30 40 50 60 MSFIMKLHRH FQRTVILLAT FCMVSIIISA YYLYSGYKQE NELSETASEV DCGDLQHLPY 70 80 90 100 110 120 QLMEVKAMKL FDASRTDPTV LVFVESQYSS LGQDIIMILE SSRFQYHIEI APGKGDLPVL 130 140 150 160 170 180 IDKMKGKYIL IIYENILKYI NMDSWNRSLL DKYCVEYGVG VIGFHKTSEK SVQSFQLKGF 190 200 210 220 230 240 PFSIYGNLAV KDCCINPHSP LIRVTKSSKL EKGSLPGTDW TVFQINHSAY QPVIFAKVKT 250 260 270 280 290 300 PENLSPSISK GAFYATIIHD LGLHDGIQRV LFGNNLNFWL HKLIFIDAIS FLSGKRLTLS 310 320 330 340 350 360 LDRYILVDID DIFVGKEGTR MNTNDVKVRL YFLKFQSSVH LPAGIQLSQF VLQLGYPGHG 370 380 IYWESLGNLG LSLTLNQLRR LCISI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of a third member of the heparan sulfate/heparin GlcNAc N-deacetylase/ N-sulfotransferase family." Aikawa J., Esko J.D. J. Biol. Chem. 274:2690-2695(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY. Tissue: Brain.
[2]	Sakakibara Y., Sanematsu F., Takami Y., Yanagisawa K., Nakayama T., Suiko M., Liu M.-C. Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-264.
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF074924 mRNA. Translation: AAD15978.1. AF076605 mRNA. Translation: AAD46061.1. AY358852 mRNA. Translation: AAQ89211.1. AC096762 Genomic DNA. No translation available. AC108201 Genomic DNA. Translation: AAY41001.1. AC110999 Genomic DNA. Translation: AAY41056.1. BC109309 mRNA. Translation: AAI09310.1. BC109310 mRNA. Translation: AAI09311.1.
IPI	IPI00329497. IPI00432131.
RefSeq	NP_004775.1. NM_004784.2.
UniGene	Hs.480596.
3D structure databases
ProteinModelPortal	O95803.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000296499.
PTM databases
PhosphoSite	O95803.
Proteomic databases
PaxDb	O95803.
PRIDE	O95803.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000296499; ENSP00000296499; ENSG00000164100.
GeneID	9348.
KEGG	hsa:9348.
UCSC	uc003ibw.3. human. uc003ibx.3. human.
Organism-specific databases
CTD	9348.
GeneCards	GC04P118954.
HGNC	HGNC:7682. NDST3.
HPA	HPA056189.
MIM	603950. gene.
neXtProt	NX_O95803.
PharmGKB	PA31488.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG267831.
HOGENOM	HOG000008010.
HOVERGEN	HBG082011.
InParanoid	O95803.
KO	K02578.
OMA	PPISKGA.
OrthoDB	EOG48KR9J.
PhylomeDB	O95803.
Enzyme and pathway databases
BioCyc	MetaCyc:HS09011-MONOMER.
BRENDA	2.8.2.8. 2681.
Reactome	REACT_111217. Metabolism. REACT_116125. Disease.
UniPathway	UPA00756. UPA00862.
Gene expression databases
ArrayExpress	O95803.
Bgee	O95803.
CleanEx	HS_NDST3.
Genevestigator	O95803.
GermOnline	ENSG00000164100. Homo sapiens.
Family and domain databases
InterPro	IPR021930. Heparan_SO4_deacetylase. IPR027417. P-loop_NTPase. IPR000863. Sulfotransferase_dom. [Graphical view]
Pfam	PF12062. HSNSD. 1 hit. PF00685. Sulfotransfer_1. 1 hit. [Graphical view]
SUPFAM	SSF52540. SSF52540. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	9348.
NextBio	35005.
SOURCE	Search...

Entry information

Entry name

NDST3_HUMAN

Accession

Primary (citable) accession number: O95803
Secondary accession number(s): Q4W5C1 , Q4W5D0, Q6UWC5, Q9UP21

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 7, 2006
Last sequence update:	May 1, 1999
Last modified:	May 29, 2013
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.