P52850 (NDST2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2
EC=2.8.2.8

Alternative name(s):
Glucosaminyl N-deacetylase/N-sulfotransferase 2
Short name=NDST-2
Mndns
N-heparan sulfate sulfotransferase 2
Short name=N-HSST 2

Including the following 2 domains:

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

Gene names

Name:	Ndst2
Synonyms:	Hsst2

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 › Mus

Protein attributes

Sequence length	883 AA.
Sequence status	Complete.
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. 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 By similarity.
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein By similarity.
Tissue specificity	Widely expressed in adult and throughout development.
Disruption phenotype	Mice are viable and fertile but have fewer connective-tissue-type mast cells; mast cells that remain having an altered morphology and severely reduced amounts of stored histamine and mast cell proteases. Ref.6 Ref.7
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
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Hydrolase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	glycosaminoglycan biosynthetic process Traceable author statement Ref.6. Source: MGI heparan sulfate proteoglycan biosynthetic process Inferred from mutant phenotype Ref.7. 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 Traceable author statement Ref.6Ref.7. Source: MGI deacetylase activity Inferred from direct assay Ref.3. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 883	883	Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2		PRO_0000085213
Regions
	Topological domain	1 – 18	18	Cytoplasmic Potential
	Transmembrane	19 – 39	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	40 – 883	844	Lumenal Potential
	Nucleotide binding	613 – 617	5	PAPS By similarity
	Nucleotide binding	832 – 836	5	PAPS By similarity
	Region	41 – 597	557	Heparan sulfate N-deacetylase 2
	Region	598 – 883	286	Heparan sulfate N-sulfotransferase 2
Sites
	Active site	613	1	For sulfotransferase activity By similarity
	Binding site	711	1	PAPS By similarity
Amino acid modifications
	Glycosylation	233	1	N-linked (GlcNAc...) Potential
	Glycosylation	350	1	N-linked (GlcNAc...) Potential
	Glycosylation	400	1	N-linked (GlcNAc...) Potential
	Glycosylation	666	1	N-linked (GlcNAc...) Potential
	Glycosylation	726	1	N-linked (GlcNAc...) Potential
	Glycosylation	802	1	N-linked (GlcNAc...) Potential
	Disulfide bond	817 ↔ 827		By similarity
Experimental info
	Sequence conflict	118	1	A → V in CAA53479. Ref.2
	Sequence conflict	396	1	Missing in CAA53479. Ref.2
	Sequence conflict	461	1	P → L in BAE29307. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P52850 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 8AC8C7BEF5B8EED8	FASTA	883	101,202
	10 20 30 40 50 60 MLQLWKVVRP ARQLELHRLI LLLIGFSLVS MGFLAYYVST SPKAKEPLPL PLGDCSSSGA 70 80 90 100 110 120 AGPGPARPPV PPRPQRPPET TRTEPVVLVF VESAYSQLGQ EIVAILESSR FRYSTELAPG 130 140 150 160 170 180 RGDMPTLTDH THGRYVLVIY ENLLKYVNLD AWSRELLDRY CVEYGVGIIG FFRAREHSLL 190 200 210 220 230 240 SAQLKGFPLF LHSNLGLRDY QVNPSAPLLH LTRPSRLEPG PLPGDDWTIF QSNHSTYEPV 250 260 270 280 290 300 LIASHRPAEL SMPGPVLRRA RLPTVVQDLG LHDGIQRVLF GHGLSFWLHK LVFVDAVAYL 310 320 330 340 350 360 TGKRLCLDLD RYILVDIDDI FVGKEGTRMK VADVEALLTT QNKLRTLVPN FTFNLGFSGK 370 380 390 400 410 420 FYHTGTEEED AGDDMLLKHR REFWWFPHMW SHMQPHLFHN RSVLADQMRL NKQFALEHGI 430 440 450 460 470 480 PTDLGYAVAP HHSGVYPIHS QLYEAWKSVW GIQVTSTEEY PHLRPARYRR GFIHNGIMVL 490 500 510 520 530 540 PRQTCGLFTH TIFYNEYPGG SRELDRSIRG GELFLTVLLN PISVFMTHLS NYGNDRLGLY 550 560 570 580 590 600 TFESLVRFLQ CWTRLRLQTL PPVPLAQKYF ELFPQERSPL WQNPCDDKRH KDIWSKEKTC 610 620 630 640 650 660 DRLPKFLIVG PQKTGTTAIH FFLSLHPAVT SSFPSPSTFE EIQFFNGPNY HKGIDWYMDF 670 680 690 700 710 720 FPVPSNASTD FLFEKSATYF DSEVVPRRGA ALLPRAKIIT VLINPADRAY SWYQHQRAHG 730 740 750 760 770 780 DPIALNYTFY QVISASSQAP LLLRSLQNRC LVPGYYSTHL QRWLTYYPSG QLLIMDGQEL 790 800 810 820 830 840 RVNPAASMEI IQKFLGITPF LNYTRTLRFD EDKGFWCQGL EGGKTRCLGR SKGRRYPDMD 850 860 870 880 MESRLFLTDF FRNHNLELSK LLSRLGQPAP LWLREELQHS SVG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of a glycosaminoglycan N-acetylglucosaminyl N-deacetylase/N-sulfotransferase from a heparin-producing cell line." Orellana A., Hirschberg C.B., Wei Z., Swiedler S.J., Ishihara M. J. Biol. Chem. 269:2270-2276(1994) [PubMed: 8294485] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: LAF1.
[2]	"cDNA cloning and sequencing of mouse mastocytoma glucosaminyl N-deacetylase/N-sulfotransferase, an enzyme involved in the biosynthesis of heparin." Eriksson I., Sandbaeck D., Ek B., Lindahl U., Kjellen L. J. Biol. Chem. 269:10438-10443(1994) [PubMed: 8144627] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 360-375; 568-580; 697-710 AND 813-823. Strain: Leaden X A1.
[3]	"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]. Strain: BALB/c. Tissue: Lung.
[4]	"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]. Strain: C57BL/6J. Tissue: Bone marrow.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Heparin is essential for the storage of specific granule proteases in mast cells." Humphries D.E., Wong G.W., Friend D.S., Gurish M.F., Qiu W.-T., Huang C., Sharpe A.H., Stevens R.L. Nature 400:769-772(1999) [PubMed: 10466726] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[7]	"Abnormal mast cells in mice deficient in a heparin-synthesizing enzyme." Forsberg E., Pejler G., Ringvall M., Lunderius C., Tomasini-Johansson B., Kusche-Gullberg M., Eriksson I., Ledin J., Hellman L., Kjellen L. Nature 400:773-776(1999) [PubMed: 10466727] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U02304 mRNA. Translation: AAC52137.1. X75885 mRNA. Translation: CAA53479.1. AF074925 mRNA. Translation: AAD15979.1. AK150100 mRNA. Translation: BAE29307.1. BC110480 mRNA. Translation: AAI10481.1.
IPI	IPI00323726.
PIR	A49733.
RefSeq	NP_034941.2. NM_010811.2.
UniGene	Mm.4084.
3D structure databases
ProteinModelPortal	P52850.
SMR	P52850. Positions 579-878.
ModBase	Search...
Protein-protein interaction databases
STRING	P52850.
PTM databases
PhosphoSite	P52850.
Proteomic databases
PRIDE	P52850.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000047490; ENSMUSP00000040227; ENSMUSG00000039308.
GeneID	17423.
KEGG	mmu:17423.
UCSC	uc007sks.1. mouse.
Organism-specific databases
CTD	8509.
MGI	MGI:97040. Ndst2.
Phylogenomic databases
eggNOG	roNOG12390.
GeneTree	ENSGT00560000076777.
HOGENOM	HBG356867.
HOVERGEN	HBG082011.
InParanoid	P52850.
OMA	VESIYSQ.
OrthoDB	EOG4NP72R.
PhylomeDB	P52850.
Gene expression databases
ArrayExpress	P52850.
Bgee	P52850.
Genevestigator	P52850.
GermOnline	ENSMUSG00000039308. Mus musculus.
Family and domain databases
InterPro	IPR021930. Heparan_SO4_deacetylase. IPR000863. Sulfotransferase_dom. [Graphical view]
KO	K02577.
Pfam	PF12062. HSNSD. 1 hit. PF00685. Sulfotransfer_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	292042.
SOURCE	Search...

Entry information

Entry name

NDST2_MOUSE

Accession

Primary (citable) accession number: P52850
Secondary accession number(s): Q3UDF4, Q549P5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 16, 2011
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