Reviewed, UniProtKB/Swiss-Prot Q9XZ08 (EXT3_DROME)

Names and origin

Protein names

Recommended name:
    Exostosin-3
    EC=2.4.1.223
Alternative name(s):
    Protein brother of tout-velu

Gene names

Name:	botv
Synonyms:	DEXT3
ORF Names:	CG15110

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

Protein attributes

Sequence length	972 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Glycosyltransferase required for the biosynthesis of heparan-sulfate and responsible for the alternating addition of beta-1-4-linked glucuronic acid (GlcA) and alpha-1-4-linked N-acetylglucosamine (GlcNAc) units to nascent heparan sulfate chains. Plays a central role in diffusion of morphogens hedgehog (hh), wingless (wg) and Decapentaplegic (dpp) via its role in heparan sulfate proteoglycans (HSPGs) biosynthesis, HSPGs being required for movement of Hh, Dpp and wg morphogens. Ref.5 Ref.6 Ref.7
Catalytic activity	UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-xylosyl-proteoglycan = UDP + alpha-N-acetyl-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-xylosyl-proteoglycan. Ref.1
Pathway	Glycan metabolism; heparan sulfate biosynthesis.
Subcellular location	Endoplasmic reticulum membrane; Single-pass type II membrane protein By similarity. Golgi apparatus membrane; Single-pass type II membrane protein By similarity.
Tissue specificity	In wing imaginal disk, it is ubiquitously expressed. Ref.5
Developmental stage	Expressed throughout the developmental stages in both head and body from males and females. Ref.1
Sequence similarities	Belongs to the glycosyltransferase 47 family.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Domain	Signal-anchor Transmembrane
Molecular function	Developmental protein Glycosyltransferase Transferase
PTM	Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	N-acetylglucosamine metabolic process Inferred from sequence or structural similarity. Source: UniProtKB Wnt receptor signaling pathway Ref.5 Ref.6 Inferred from mutant phenotype. Source: UniProtKB decapentaplegic receptor signaling pathway Ref.5 Ref.6 Inferred from mutant phenotype. Source: UniProtKB heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process Ref.5 Inferred from mutant phenotype. Source: FlyBase heparin biosynthetic process Ref.1 Inferred from direct assay. Source: UniProtKB multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW smoothened signaling pathway Ref.5 Ref.6 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	Golgi apparatus Ref.6 Inferred from direct assay. Source: UniProtKB integral to membrane Ref.1 Non-traceable author statement. Source: UniProtKB intrinsic to endoplasmic reticulum membrane Inferred from electronic annotation. Source: InterPro
Molecular function	glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 972	972	Exostosin-3		PRO_0000149666
Regions
	Topological domain	1 – 55	55	Cytoplasmic Potential
	Transmembrane	56 – 76	21	Signal-anchor for type II membrane protein Potential
	Topological domain	77 – 972	896	Lumenal Potential
Amino acid modifications
	Glycosylation	218	1	N-linked (GlcNAc...) Potential
	Glycosylation	606	1	N-linked (GlcNAc...) Potential
	Glycosylation	643	1	N-linked (GlcNAc...) Potential
	Glycosylation	843	1	N-linked (GlcNAc...) Potential
Experimental info
	Mutagenesis	669	1	P → L in botv510; induces defects in wing patterning due to impaired movement of morphogens. Ref.5
	Mutagenesis	707	1	G → D in botv8; induces defects in wing patterning due to impaired movement of morphogens. Ref.6
	Mutagenesis	821	1	G → D in botv514; induces defects in wing patterning due to impaired movement of morphogens. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q9XZ08-1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 2A111BD6912FFCCA	FASTA	972	111,000
	10 20 30 40 50 60 MPPAYDLGHS GEAYQPLDTG SGGGNEACAP NSSSAQIRHS MGFRTSWMRQ FRRYKLPMVL 70 80 90 100 110 120 LMLLFLVSCL AYRILSVEQD APPLDLHRSS PLLDAYEDFS AMRAGDLKMR IEEMVRIKST 130 140 150 160 170 180 VSVELRELES RRQKLQSDIS QYNQKIEELK QELLREQTEL ERLKISVEQA QVAQREAVQR 190 200 210 220 230 240 NTPDLALPRS LLPNTLPRKS NPITGGMAAS CEMHNCFNHS RCSLTSGFPV YLYDPDEHSV 250 260 270 280 290 300 QRKGYDIDGF LKTTLKQTLG YNAHIVKDPK HACIYLVLVG EALLEQDLLR NNRYAAQEAE 310 320 330 340 350 360 HQQPSTPTLE NDCPVDMEKL YSLPYWGGDG RNHVLLNLAR RDLTSHRTNP LYRQNTMRAI 370 380 390 400 410 420 VVQSAFEREQ FRPGYDLIVP PILGPPGGDV WQECAEMVPA RRKYLLTYQG ELRPKQSSLN 430 440 450 460 470 480 PLDAFILEHL ADMAKGATQD QFVLQFQCVP ATEQQEGDSL PDWTLCGSDS SRRQLLKDST 490 500 510 520 530 540 FSLILPPLNG RVSSTLMLAR IYEALRSGAV PVILGADELR LPYAETVDWR RTALLLPKAR 550 560 570 580 590 600 ITELHFLLRA VQDADLLLLR RQGRLIWERY LSSVQATVDT VIASLRDRLG IPPRPVPSVI 610 620 630 640 650 660 AQSVFNSTFI PLKSDPPVGL DTEPEESLGP IEPPYPSPAF RRNYTILRMQ AKEAWNDWLD 670 680 690 700 710 720 PFYLYPQLPF DPALPSEAKF MGSHTGFRPI GKGLGGAGKE FGESLGGNYP REQFTIVMLT 730 740 750 760 770 780 YEREQVLMDS LGRLYGLPYL HKVVVVWNSP KPPLDDLRWP DIGVPVAVLR APRNSLNNRF 790 800 810 820 830 840 LPFDVIETEA VLSVDDDAHL RHDEILFGFR VWREHRDRVV GFPGRYHAWD LGNPNGQWHY 850 860 870 880 890 900 NSNYSCELSM VLTGAAFVHK YYLYLYTYHL PQAIRDKVDE YMNCEDIAMN FLVSHITRKP 910 920 930 940 950 960 PVKVTSRWTF RCPGCPVSLS EDDTHFQERH KCINFFSRVF GYTPLLNTQY RADSILFKTR 970 IPHDKQKCFK YI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Demonstration of a novel gene DEXT3 of Drosophila melanogaster as the essential N-acetylglucosamine transferase in the heparan sulfate biosynthesis: chain initiation and elongation." Kim B.-T., Kitagawa H., Tamura J., Kusche-Gullberg M., Lindahl U., Sugahara K. J. Biol. Chem. 277:13659-13665(2002) [PubMed: 11832488] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY, DEVELOPMENTAL STAGE. Tissue: Embryo.
[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. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., 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. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION.
[4]	"A Drosophila complementary DNA resource." Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M., Harvey D.A. Science 287:2222-2224(2000) [PubMed: 10731138] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Berkeley. Tissue: Embryo.
[5]	"Three Drosophila EXT genes shape morphogen gradients through synthesis of heparan sulfate proteoglycans." Takei Y., Ozawa Y., Sato M., Watanabe A., Tabata T. Development 131:73-82(2004) [PubMed: 14645127] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF PRO-669 AND GLY-821.
[6]	"Distinct and collaborative roles of Drosophila EXT family proteins in morphogen signalling and gradient formation." Han C., Belenkaya T.Y., Khodoun M., Tauchi M., Lin X., Lin X. Development 131:1563-1575(2004) [PubMed: 14998928] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLY-707.
[7]	"Abrogation of heparan sulfate synthesis in Drosophila disrupts the Wingless, Hedgehog and Decapentaplegic signaling pathways." Bornemann D.J., Duncan J.E., Staatz W., Selleck S., Warrior R. Development 131:1927-1938(2004) [PubMed: 15056609] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB077850 mRNA. Translation: BAB89399.1. AE013599 Genomic DNA. Translation: AAF57601.1. AF132161 mRNA. Translation: AAD34749.1.
RefSeq	NP_523790.1.
UniGene	Dm.3207
3D structure databases
SMR	Q9XZ08. Positions 711-958.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9XZ08. 1 interaction.
STRING	Q9XZ08.
Protein family/group databases
CAZy	GT47. Glycosyltransferase Family 47. GT64. Glycosyltransferase Family 64.
Proteomic databases
PRIDE	Q9XZ08.
Genome annotation databases
Ensembl	FBtr0086579; FBpp0085763; FBgn0027535; Drosophila melanogaster. [Genome view]
GeneID	37198.
KEGG	dme:Dmel_CG15110.
NMPDR	fig|7227.3.peg.6287.
Organism-specific databases
CTD	37198.
FlyBase	FBgn0027535. botv.
Phylogenomic databases
eggNOG	inNOG05765.
InParanoid	Q9XZ08.
OMA	ARANVYV.
OrthoDB	EOG9933QV.
PhylomeDB	Q9XZ08.
Enzyme and pathway databases
BRENDA	2.4.1.223. 48. 2.4.1.224. 48.
Gene expression databases
GermOnline	CG15110. Drosophila melanogaster.
Family and domain databases
InterPro	IPR004263. Exostosin. IPR015338. HexNAc_Trfase_a. [Graphical view]
Pfam	PF03016. Exostosin. 1 hit. PF09258. Glyco_transf_64. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	802444.

Entry information

Entry name

EXT3_DROME

Accession

Primary (citable) accession number: Q9XZ08

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	November 1, 1999
Last modified:	January 19, 2010
This is version 66 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project