Q9V730 (EXT1_DROME) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Mandibulata › Pancrustacea › Hexapoda › Insecta › Dicondylia › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Eremoneura › Cyclorrhapha › Schizophora › Acalyptratae › Ephydroidea › Drosophilidae › Drosophilinae › Drosophilini › Drosophilina › Drosophiliti › Drosophila › Sophophora › melanogaster group › melanogaster subgroup

Protein attributes

Sequence length	760 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. 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. Glycan metabolism; heparan sulfate biosynthesis. Glycan metabolism; heparin biosynthesis.
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 Transmembrane helix
Molecular function	Developmental protein Glycosyltransferase Transferase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	N-acetylglucosamine metabolic process Inferred from sequence or structural similarity. Source: UniProtKB Wnt receptor signaling pathway Inferred from mutant phenotype Ref.13. Source: UniProtKB decapentaplegic signaling pathway Inferred from mutant phenotype Ref.12Ref.13. Source: UniProtKB germ cell migration Inferred from mutant phenotype PubMed 17409068. Source: FlyBase heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process Inferred from mutant phenotype Ref.10. Source: FlyBase heparin biosynthetic process Inferred from mutant phenotype Ref.13. Source: FlyBase intracellular distribution of mitochondria Inferred from mutant phenotype PubMed 19571145. Source: FlyBase multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW protein glycosylation Inferred from electronic annotation. Source: UniProtKB-UniPathway regulation of smoothened signaling pathway Inferred from mutant phenotype Ref.9Ref.1. Source: UniProtKB smoothened signaling pathway Inferred from mutant phenotype Ref.12Ref.13. Source: UniProtKB synapse organization Inferred from mutant phenotype PubMed 19571145. Source: FlyBase synaptic vesicle endocytosis Inferred from mutant phenotype PubMed 19571145. Source: FlyBase
Cellular_component	Golgi apparatus Inferred from direct assay Ref.6Ref.12. Source: UniProtKB Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum Inferred from direct assay Ref.6Ref.12. Source: UniProtKB integral to membrane Non-traceable author statement Ref.1. 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
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ext2	Q9Y169	3	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	Helical; 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 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF083889 mRNA. Translation: AAC32397.1. Frameshift. AB221351 mRNA. Translation: BAE78509.1. AE013599 Genomic DNA. Translation: AAF58236.1. BT021403 mRNA. Translation: AAX33551.1.
RefSeq	NP_001260971.1. NM_001274042.1. NP_477231.1. NM_057883.3.
UniGene	Dm.2966.
3D structure databases
ProteinModelPortal	Q9V730.
SMR	Q9V730. Positions 562-734.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9V730. 4 interactions.
MINT	MINT-7953341.
Protein family/group databases
CAZy	GT47. Glycosyltransferase Family 47. GT64. Glycosyltransferase Family 64.
Proteomic databases
PaxDb	Q9V730.
PRIDE	Q9V730.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0087495; FBpp0086624; FBgn0020245. FBtr0333164; FBpp0305367; FBgn0020245.
GeneID	36614.
KEGG	dme:Dmel_CG10117.
Organism-specific databases
CTD	36614.
FlyBase	FBgn0020245. ttv.
Phylogenomic databases
eggNOG	NOG272619.
GeneTree	ENSGT00550000074496.
InParanoid	Q5BI21.
KO	K02366.
OMA	WEAYFNS.
OrthoDB	EOG4GF1W3.
PhylomeDB	Q9V730.
Enzyme and pathway databases
SignaLink	Q9V730.
UniPathway	UPA00378. UPA00756. UPA00862.
Gene expression databases
Bgee	Q9V730.
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
ChiTaRS	EXT1. drosophila.
GenomeRNAi	36614.
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:	May 29, 2013
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project