Reviewed, UniProtKB/Swiss-Prot Q9V730 (EXT1_DROME)

Names and origin

Protein names

Recommended name:
    Exostosin-1
    EC=2.4.1.224
    EC=2.4.1.225
Alternative name(s):
    Protein tout-velu

Gene names

Name:	ttv
Synonyms:	DEXT1
ORF Names:	CG10117

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	760 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. Botv is the trigger of heparan sulfate chain initiation and polymerization takes place by a complex of ttv and sotv. Plays a central role in diffusion of morphogens hedgehog (hh), wingless (wg) and decapentaplegic (dpp) via its role in heparan sulfate proteoglycans (HSPGs) biosynthesis which are required for movement of hh, dpp and wg morphogens. Ref.1 Ref.2 Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Catalytic activity	UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan = UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan. Ref.6 Ref.7 UDP-alpha-D-glucuronate + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan = UDP + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan. Ref.6 Ref.7
Pathway	Protein modification; protein glycosylation. Ref.6 Ref.8 Ref.9 Ref.11 Glycan metabolism; heparan sulfate biosynthesis. Ref.6 Ref.8 Ref.9 Ref.11 Glycan metabolism; heparin biosynthesis. Ref.6 Ref.8 Ref.9 Ref.11
Subunit structure	Forms a homo/heterooligomeric complex with sotv.
Subcellular location	Endoplasmic reticulum membrane; Single-pass type II membrane protein. Golgi apparatus membrane; Single-pass type II membrane protein. Ref.6
Tissue specificity	Ubiquitously expressed in early embryos. Later (in stage 10 embryos), it is expressed at higher level in the nervous system. Ubiquitously expressed in wing imaginal disk. Ref.6 Ref.10
Developmental stage	Expressed both maternally and zygotically. Ref.1
Disruption phenotype	According to some authors (Ref.6) ttv mutants have no effect on wg signaling, while according to others (Ref.10, Ref.11 and Ref.13) wg signaling is affected. Such discrepancy may be explained by the fact that the absence ttv could be partially compensated by the intact sotv protein. Ref.6 Ref.10 Ref.11 Ref.13
Miscellaneous	'Tout velu' means 'very hairy' in French.
Sequence similarities	Belongs to the glycosyltransferase 47 family.
Sequence caution	The sequence AAC32397.1 differs from that shown. Reason: Frameshift at positions 694 and 702.

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.12 Ref.13 Inferred from mutant phenotype. Source: UniProtKB decapentaplegic receptor signaling pathway Ref.12 Ref.13 Inferred from mutant phenotype. Source: UniProtKB germ cell migration Inferred from mutant phenotype. Source: FlyBase heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process Ref.10 Inferred from mutant phenotype. Source: FlyBase heparin biosynthetic process Ref.13 Inferred from mutant phenotype. Source: FlyBase multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW regulation of smoothened signaling pathway Ref.1 Ref.9 Inferred from mutant phenotype. Source: UniProtKB smoothened signaling pathway Ref.12 Ref.13 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Ref.1 Non-traceable author statement. Source: UniProtKB intrinsic to endoplasmic reticulum membrane Inferred from electronic annotation. Source: InterPro
Molecular function	N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB protein binding Ref.2 Ref.12 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ext2	Q9Y169	1	EBI-166374,EBI-142791

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 760	760	Exostosin-1		PRO_0000149664
Regions
	Topological domain	1 – 6	6	Cytoplasmic Potential
	Transmembrane	7 – 25	19	Signal-anchor for type II membrane protein Potential
	Topological domain	26 – 760	735	Lumenal Potential
Amino acid modifications
	Glycosylation	71	1	N-linked (GlcNAc...) Potential
	Glycosylation	327	1	N-linked (GlcNAc...) Potential
	Glycosylation	476	1	N-linked (GlcNAc...) Potential
Experimental info
	Mutagenesis	447	1	G → D in ttv205; induces defects in wing patterning due to impaired movement of morphogens. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	Q9V730-1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: F6369F0BA206DEA9	FASTA	760	87,309
	10 20 30 40 50 60 MQAKKRYILV FVSCAFLAYA YFGGYRLKVS PLRPRRAQHE SAKDGGVQPH EQLPSFLGAH 70 80 90 100 110 120 DMQELQLLQS NQSKSLDSSK HLVTRKPDCR METCFDFTRC YDRFLVYIYP PEPLNSLGAA 130 140 150 160 170 180 PPTSANYQKI LTAIQESRYY TSDPTAACLF VLGIDTLDRD SLSEDYVRNV PSRLARLPYW 190 200 210 220 230 240 NNGRNHIIFN LYSGTWPDYA ENSLGFDAGE AILAKASMGV LQLRHGFDVS IPLFHKQFPL 250 260 270 280 290 300 RAGATGTVQS NNFPANKKYL LAFKGKRYVH GIGSETRNSL FHLHNGRDMV LVTTCRHGKS 310 320 330 340 350 360 WRELQDNRCD EDNREYDRYD YETLLQNSTF CLVPRGRRLG SFRFLEALQA GCIPVLLSNA 370 380 390 400 410 420 WVLPFESKID WKQAAIWADE RLLLQVPDIV RSIPAERIFA LRQQTQVLWE RYFGSIEKIV 430 440 450 460 470 480 FTTFEIIRER LPDYPVRSSL VWNSSPGALL TLPTFADSSR YMPFLLNSMG AEPRHNYTAV 490 500 510 520 530 540 IYVQIGAALG PNAALYKLVR TITKSQFVER ILVLWAADRP LPLKKRWPPT SHIPLHVISL 550 560 570 580 590 600 GGSTRSQGAG PTSQTTEGRP SISQRFLPYD EIQTDAVLSL DEDAILNTDE LDFAYTVWRD 610 620 630 640 650 660 FPERIVGYPA RAHFWDDSKN AWGYTSKWTN YYSIVLTGAA FYHRYYNYLY TNWLSLLLLK 670 680 690 700 710 720 TVQQSSNCED ILMNLLVSHV TRKPPIKVTQ RKGYKDRETG RSPWNDPDHF IQRQSCLNTF 730 740 750 760 AAVFGYMPLI RSNLRMDPML YRDPVSNLRK KYRQIELVGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion." Bellaiche Y., The I., Perrimon N. Nature 394:85-88(1998) [PubMed: 9665133] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, MEMBRANE TOPOLOGY, DEVELOPMENTAL STAGE.
[2]	"Heparan sulfate polymerization in Drosophila." Izumikawa T., Egusa N., Taniguchi F., Sugahara K., Kitagawa H. J. Biol. Chem. 281:1929-1934(2006) [PubMed: 16303756] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH SOTV.
[3]	"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.
[4]	"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.
[5]	Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M., Park S., Wan K.H., Yu C., Rubin G.M., Celniker S.E. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Berkeley. Tissue: Embryo.
[6]	"Hedgehog movement is regulated through tout velu-dependent synthesis of a heparan sulfate proteoglycan." The I., Bellaiche Y., Perrimon N. Mol. Cell 4:633-639(1999) [PubMed: 10549295] [Abstract] Cited for: FUNCTION IN HH PATHWAY, ENZYME ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[7]	"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: ENZYME ACTIVITY.
[8]	"Structural analysis of glycosaminoglycans in animals bearing mutations in sugarless, sulfateless, and tout-velu. Drosophila homologues of vertebrate genes encoding glycosaminoglycan biosynthetic enzymes." Toyoda H., Kinoshita-Toyoda A., Fox B., Selleck S.B. J. Biol. Chem. 275:21856-21861(2000) [PubMed: 10806213] [Abstract] Cited for: FUNCTION IN HH PATHWAY.
[9]	"Cholesterol modification of hedgehog is required for trafficking and movement, revealing an asymmetric cellular response to hedgehog." Gallet A., Rodriguez R., Ruel L., Therond P.P. Dev. Cell 4:191-204(2003) [PubMed: 12586063] [Abstract] Cited for: FUNCTION IN HH PATHWAY.
[10]	"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 GLY-447, DISRUPTION PHENOTYPE.
[11]	"Drosophila glypicans control the cell-to-cell movement of Hedgehog by a dynamin-independent process." Han C., Belenkaya T.Y., Wang B., Lin X. Development 131:601-611(2004) [PubMed: 14729575] [Abstract] Cited for: FUNCTION IN HH PATHWAY, DISRUPTION PHENOTYPE.
[12]	"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.
[13]	"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, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF083889 mRNA. Translation: AAC32397.1. Frameshift. AB221351 mRNA. Translation: BAE78509.1. AE013599 Genomic DNA. Translation: AAF58236.1. BT021403 mRNA. Translation: AAX33551.1.
RefSeq	NP_477231.1.
UniGene	Dm.2966
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9V730. 4 interactions.
Protein family/group databases
CAZy	GT47. Glycosyltransferase Family 47. GT64. Glycosyltransferase Family 64.
Proteomic databases
PRIDE	Q9V730.
Genome annotation databases
Ensembl	FBgn0020245. Drosophila melanogaster. [Contig view]
GeneID	36614.
KEGG	dme:Dmel_CG10117.
NMPDR	fig|7227.3.peg.5244.
Organism-specific databases
FlyBase	FBgn0020245. ttv.
Phylogenomic databases
HOGENOM	Q9V730.
OMA	Q9V730. QMSNCED.
Enzyme and pathway databases
BRENDA	2.4.1.224. 48. 2.4.1.225. 48.
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	799500.

Entry information

Entry name

EXT1_DROME

Accession

Primary (citable) accession number: Q9V730
Secondary accession number(s): O76796, Q5BI21

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	May 1, 2000
Last modified:	June 16, 2009
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