Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase

Names and origin

Protein names

Recommended name:
    Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase
    EC=2.8.2.8
Alternative name(s):
    Glucosaminyl N-deacetylase/N-sulfotransferase
    Sulfateless
Including 2 domains:
  Recommended name:
      Heparan sulfate N-deacetylase
      EC=3.-.-.-
  Recommended name:
      Heparan sulfate N-sulfotransferase
      EC=2.8.2.-

Gene names

Name:	sfl
ORF Names:	CG8339

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

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Protein attributes

Sequence length	1048 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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 diffusion of morphogen wingless (wg) via its role in heparan sulfate proteoglycans (HSPGs) biosynthesis, HSPGs being required for movement of wg morphogens. Required for wg signaling during both embryonic and imaginal disk development. Also required for FGF receptor signaling.
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 proteinBy similarity.
Sequence similarities	Belongs to the sulfotransferase 1 family. NDST subfamily.
Caution	It is uncertain whether Met-1 or Met-154 is the initiator.

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Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Golgi apparatus Membrane
Domain	Signal-anchor Transmembrane
Molecular function	Hydrolase Transferase
PTM	Glycoprotein
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Ref.1 Inferred from mutant phenotype. Source: UniProtKB epithelial cell migration, open tracheal system Ref.4 Inferred from mutant phenotype. Source: UniProtKB fibroblast growth factor receptor signaling pathway Ref.4 Inferred from mutant phenotype. Source: UniProtKB glycosaminoglycan biosynthetic process Inferred from mutant phenotype. Source: UniProtKB heart development Non-traceable author statement. Source: FlyBase heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process Inferred from mutant phenotype. Source: UniProtKB mesoderm migration Ref.4 Inferred from mutant phenotype. Source: UniProtKB primary branching, open tracheal system Traceable author statement. Source: FlyBase segment polarity determination Inferred from mutant phenotype. Source: FlyBase
Molecular function	[heparan sulfate]-glucosamine N-sulfotransferase activity Traceable author statement. Source: FlyBase protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
Cdc27	Q9VS37	1	EBI-183090,EBI-175583

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 1048

1048

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase

Regions

Topological domain

1 – 172

172

Cytoplasmic Potential

Transmembrane

173 – 192

20

Signal-anchor for type II membrane protein Potential

Topological domain

193 – 1048

856

Lumenal Potential

Nucleotide binding

768 – 772

5

PAPS By similarity

Nucleotide binding

998 – 1002

5

PAPS By similarity

Region

192 – 752

561

Heparan sulfate N-deacetylase

Region

753 – 1048

296

Heparan sulfate N-sulfotransferase

Sites

Active site

768

1

For sulfotransferase activity By similarity

Binding site

877

1

PAPS By similarity

Amino acid modifications

Glycosylation

388

1

N-linked (GlcNAc...) Potential

Glycosylation

555

1

N-linked (GlcNAc...) Potential

Glycosylation

823

1

N-linked (GlcNAc...) Potential

Glycosylation

892

1

N-linked (GlcNAc...) Potential

Disulfide bond

983 ↔ 993

By similarity

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Sequences

Sequence

Length

Mass (Da)

Tools

Q9V3L1-1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: A7E56155578D564E
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FASTA

1,048

118,590

        10         20         30         40         50         60 
MTISGGNQHN NNANRKYEKL IKQPQMQFGS SVTGTQTDVD SCRDADADAN AVRQDFSNFN 

        70         80         90        100        110        120 
KHFGNGHAIT DRTMLLRLED DVTTAAGIVT YKGKSNGNGN GNGNGSIGSI SLDFNGSPTS 

       130        140        150        160        170        180 
STSIGIASGS SSNTHLASGG GVGGIGGSEP AGWMCHCCNL IARRCFGINV RRCVLALLAI 

       190        200        210        220        230        240 
TMVSIFYYTH YVDTGVFNGL IQRDTHPAPI INCRMINSGG KHIRNASPAP DHRSEARLRI 

       250        260        270        280        290        300 
DPKVLVFVET TYSGLGRDIA ELLVYNRIKY KIEVAGKSLP VLTNLDKGRY GVIVFENLDK 

       310        320        330        340        350        360 
YLNMDKWNRE LLDKYCREYS VGIVGFVSPS EETLVGAQLR DFPLFVNTNL RLRDASLNPL 

       370        380        390        400        410        420 
SSVLRLTRAG ETAWGALPGD DWAVFQHNHS TYEPVEWAQR NTQEYPADSV GQVQLPLTTV 

       430        440        450        460        470        480 
LQDRGQLDGI QRVLFGSSLR FWLHRLVFLD ALSYLSHGQL SLNLERMILV DIDDIFVGEK 

       490        500        510        520        530        540 
GTRLRPDDVR ALIATQKNIA AMVPGFRFNL GFSGKYYHHG TREENLGDDF LLQNVQEFNW 

       550        560        570        580        590        600 
FSHMWKHQQP HLYDNLTLLM AEMHLNYAFA VDHNIPTDSG YSISPHHSGV YPAHELLYMA 

       610        620        630        640        650        660 
WKKVWNVKVT STEEYPHLRP ARLRRGFIHR NIMVLPRQTC GLFTHTMYID RYPGGRDKLD 

       670        680        690        700        710        720 
ESIQGGELFQ TIVYNPINIF MTHMSNYGSD RLALYTFQSV IKFLQCWTNL KLASAPPVQL 

       730        740        750        760        770        780 
AEMYFRLHPE EVDPVWGNPC DDVRHKKIWS KTKNCDSLPK FLVIGPQKTG TTALYTFLSM 

       790        800        810        820        830        840 
HGSIASNIAS PETFEEVQFF NGNNYYRGLD WYMDFFPSES LPNTSSPMPT QLGSPRFMFE 

       850        860        870        880        890        900 
KSATYFDGEA VPKRSHALLP HAKIVTILIS PAKRAYSWYQ HQRSHGDVIA NNYSFYQVIT 

       910        920        930        940        950        960 
ASDSAPRALK DLRNRCLNPG KYAQHLEHWL AYYPAQQLHI IDGEQLRLNP IDVMNELQRF 

       970        980        990       1000       1010       1020 
LKIQPLLDYS NHLRYDVKKG FYCQAVSEKR NKCLGKSKGR QYPAMDERSA KLLQRYYLNH 

      1030       1040 
NTALVKLLKK LGSRPIPQWL KDDLSTGT

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling." Lin X., Perrimon N. Nature 400:281-284(1999) [PubMed: 10421372] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN WG SIGNALING.
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION.
[4]	"Heparan sulfate proteoglycans are essential for FGF receptor signaling during Drosophila embryonic development." Lin X., Buff E.M., Perrimon N., Michelson A.M. Development 126:3715-3723(1999) [PubMed: 10433902] [Abstract] Cited for: FUNCTION IN FGF RECEPTOR SIGNALING.
[5]	"Structural analysis of glycosaminoglycans in Drosophila and Caenorhabditis elegans and demonstration that tout-velu, a Drosophila gene related to EXT tumor suppressors, affects heparan sulfate in vivo." Toyoda H., Kinoshita-Toyoda A., Selleck S.B. J. Biol. Chem. 275:2269-2275(2000) [PubMed: 10644674] [Abstract] Cited for: FUNCTION.
[6]	"The Wingless morphogen gradient is established by the cooperative action of Frizzled and Heparan Sulfate Proteoglycan receptors." Baeg G.-H., Selva E.M., Goodman R.M., Dasgupta R., Perrimon N. Dev. Biol. 276:89-100(2004) [PubMed: 15531366] [Abstract] Cited for: FUNCTION.

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Cross-references

Sequence databases
	AF175689 mRNA. Translation: AAD51842.1. AE014296 Genomic DNA. Translation: AAF50658.1.
RefSeq	NP_523946.1.
UniGene	Dm.4995
3D structure databases
HSSP	HSSP built from PDB template 1NST based on UniProtKB P52848.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9V3L1.
Genome annotation databases
Ensembl	CG8339. Drosophila melanogaster. [Contig view]
GeneID	38736.
KEGG	dme:Dmel_CG8339.
NMPDR	fig\|7227.3.peg.8544.
Organism-specific databases
FlyBase	FBgn0020251. sfl.
Phylogenomic databases
HOGENOM	Q9V3L1.
Gene expression databases
ArrayExpress	Q9V3L1.
GermOnline	CG8339. Drosophila melanogaster.
Family and domain databases
InterPro	IPR000863. Sulphotransferase. [Graphical view]
Pfam	PF00685. Sulfotransfer_1. 1 hit. [Graphical view]
ProDom	Q9V3L1. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
ProtoNet	Search...

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Entry information

Entry name

NDST_DROME

Accession

Primary (citable) accession number: Q9V3L1

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2005
Last sequence update:	May 1, 2000
Last modified:	July 22, 2008
This is version 56 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project

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Relevant documents

Drosophila

Drosophila: entries, gene names and cross-references to FlyBase

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents