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Q3UHN9 (NDST1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
N-heparan sulfate sulfotransferase 1
Short name=N-HSST 1
[Heparan sulfate]-glucosamine N-sulfotransferase 1
Short name=HSNST 1

Including the following 2 domains:

  1. Heparan sulfate N-deacetylase 1
    EC=3.-.-.-
  2. Heparan sulfate N-sulfotransferase 1
    EC=2.8.2.-
Gene names
Name:Ndst1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length882 AA.
Sequence statusComplete.
Protein existenceEvidence 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 disaccharide 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.5 Ref.6 Ref.8 Ref.9 Ref.10

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.5 Ref.6 Ref.8 Ref.9

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 processInflammatory response
   Cellular componentGolgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionHydrolase
Transferase
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processMAPK cascade

Inferred from mutant phenotype Ref.9. Source: MGI

embryo development

Inferred from genetic interaction Ref.9. Source: MGI

embryonic neurocranium morphogenesis

Inferred from mutant phenotype Ref.9. Source: MGI

embryonic viscerocranium morphogenesis

Inferred from mutant phenotype Ref.9. Source: MGI

fibroblast growth factor receptor signaling pathway

Inferred from mutant phenotype Ref.9. Source: MGI

forebrain development

Inferred from mutant phenotype Ref.9. Source: MGI

glycosaminoglycan metabolic process

Inferred from mutant phenotype Ref.9. Source: MGI

heparan sulfate proteoglycan biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

heparin biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

midbrain development

Inferred from genetic interaction Ref.9. Source: MGI

organ morphogenesis

Inferred from mutant phenotype Ref.5Ref.6. Source: MGI

polysaccharide biosynthetic process

Inferred from mutant phenotype Ref.6. Source: MGI

protein deacetylation

Traceable author statement Ref.5Ref.6. Source: MGI

protein sulfation

Inferred from mutant phenotype Ref.6. Source: MGI

respiratory gaseous exchange

Inferred from mutant phenotype Ref.5Ref.6. Source: MGI

smoothened signaling pathway

Inferred from genetic interaction Ref.9. Source: MGI

   Cellular_componentGolgi membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_function[heparan sulfate]-glucosamine N-sulfotransferase activity

Traceable author statement Ref.5Ref.6. Source: MGI

deacetylase activity

Inferred from direct assay Ref.2. Source: MGI

sulfotransferase activity

Inferred from direct assay Ref.2. Source: MGI

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 882882Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1
PRO_0000225655

Regions

Topological domain1 – 1717Cytoplasmic Potential
Transmembrane18 – 3821Helical; Signal-anchor for type II membrane protein; Potential
Topological domain39 – 882844Lumenal Potential
Nucleotide binding614 – 6185PAPS By similarity
Nucleotide binding833 – 8375PAPS By similarity
Region40 – 598559Heparan sulfate N-deacetylase 1
Region599 – 882284Heparan sulfate N-sulfotransferase 1

Sites

Active site6141For sulfotransferase activity
Binding site7121PAPS By similarity

Amino acid modifications

Glycosylation2311N-linked (GlcNAc...) Potential
Glycosylation3511N-linked (GlcNAc...) Potential
Glycosylation4011N-linked (GlcNAc...) Potential
Glycosylation6671N-linked (GlcNAc...) Potential
Disulfide bond818 ↔ 828 By similarity

Natural variations

Alternative sequence143 – 18543KYVNL…QLKGF → SISCHSSSVLQTVKGKSAAG PFAQPGRKTGHVPEGFEPGP ARV in isoform 3.
VSP_017399
Alternative sequence186 – 882697Missing in isoform 3.
VSP_017400
Alternative sequence480 – 49516VLPRQ…HTIFY → RLGDTEVKNPDKSLTS in isoform 2.
VSP_017401
Alternative sequence496 – 882387Missing in isoform 2.
VSP_017402

Experimental info

Mutagenesis4861C → W: Loss of deacetylase activity but does not affect sulfotransferase activity. Ref.7
Mutagenesis6141K → A: Loss of sulfotransferase activity but does not affect deacetylase activity. Ref.7
Sequence conflict1091F → S in BAE27818. Ref.3
Sequence conflict7891M → V in AAC17228. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 7, 2006. Version 2.
Checksum: 8BE300ABCB8E648D

FASTA882100,726
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 7023F8CAA85F2344
Show »

FASTA49555,731
Isoform 3 [UniParc].

Checksum: 4877F728103F7FCB
Show »

FASTA18520,078

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
Strain: C57BL/6J and NOD.
Tissue: Urinary bladder.
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Brain.
[5]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[7]"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] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-486 AND LYS-614.
[8]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[9]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[10]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_032332.2. NM_008306.4.
XP_006525730.1. XM_006525667.1.
XP_006525731.1. XM_006525668.1.
XP_006525732.1. XM_006525669.1.
XP_006525733.1. XM_006525670.1.
XP_006525734.1. XM_006525671.1.
XP_006525735.1. XM_006525672.1.
UniGeneMm.181862.
Mm.486185.

3D structure databases

ProteinModelPortalQ3UHN9.
SMRQ3UHN9. Positions 579-879.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-29859N.

PTM databases

PhosphoSiteQ3UHN9.

Proteomic databases

PaxDbQ3UHN9.
PRIDEQ3UHN9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000169273; ENSMUSP00000126623; ENSMUSG00000054008. [Q3UHN9-1]
GeneID15531.
KEGGmmu:15531.
UCSCuc008fat.1. mouse. [Q3UHN9-1]
uc008fav.1. mouse. [Q3UHN9-2]

Organism-specific databases

CTD3340.
MGIMGI:104719. Ndst1.

Phylogenomic databases

eggNOGNOG267831.
GeneTreeENSGT00740000115140.
HOGENOMHOG000008010.
HOVERGENHBG082011.
InParanoidQ3UHN9.
KOK02576.
OMATNTIDYH.
OrthoDBEOG7FXZXJ.
PhylomeDBQ3UHN9.
TreeFamTF313193.

Enzyme and pathway databases

UniPathwayUPA00756.
UPA00862.

Gene expression databases

BgeeQ3UHN9.
GenevestigatorQ3UHN9.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR021930. Heparan_SO4_deacetylase.
IPR027417. P-loop_NTPase.
IPR000863. Sulfotransferase_dom.
[Graphical view]
PfamPF12062. HSNSD. 1 hit.
PF00685. Sulfotransfer_1. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
ProtoNetSearch...

Other

ChiTaRSNDST1. mouse.
NextBio288464.
PROQ3UHN9.
SOURCESearch...

Entry information

Entry nameNDST1_MOUSE
AccessionPrimary (citable) accession number: Q3UHN9
Secondary accession number(s): O70353 expand/collapse secondary AC list , Q3TBX3, Q3TDS3, Q8BZE5, Q9R206
Entry history
Integrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: March 7, 2006
Last modified: April 16, 2014
This is version 84 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot