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Q9V730 (EXT1_DROME) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 93. 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·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismDrosophila melanogaster (Fruit fly) [Reference proteome]
Taxonomic identifier7227 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora

Protein attributes

Sequence length760 AA.
Sequence statusComplete.
Protein existenceEvidence 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 the 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. May interact with rti.

Subcellular location

Endoplasmic reticulum membrane; Single-pass type II membrane protein. Golgi apparatus membrane; Single-pass type II membrane protein. Note: Localization to the Golgi may be regulated by rti. Ref.6 Ref.14

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 of 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 processWnt signaling pathway
   Cellular componentEndoplasmic reticulum
Golgi apparatus
Membrane
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
Glycosyltransferase
Transferase
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processN-acetylglucosamine metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

Wnt signaling pathway

Inferred from mutant phenotype Ref.13. Source: UniProtKB

axon guidance

Inferred from genetic interaction PubMed 19574454. Source: FlyBase

decapentaplegic signaling pathway

Inferred from mutant phenotype Ref.12Ref.13. Source: UniProtKB

germ cell migration

Inferred from mutant phenotype PubMed 17409068. Source: FlyBase

glycosaminoglycan biosynthetic process

Inferred from mutant phenotype Ref.7Ref.8. Source: UniProtKB

heparan sulfate proteoglycan biosynthetic process

Inferred from mutant phenotype Ref.6Ref.10Ref.2. Source: UniProtKB

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

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_componentGolgi 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 component of membrane

Non-traceable author statement Ref.1. Source: UniProtKB

intrinsic component of endoplasmic reticulum membrane

Inferred from electronic annotation. Source: InterPro

   Molecular_functionN-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity

Inferred from sequence or structural similarity. Source: UniProtKB

acetylglucosaminyltransferase activity

Non-traceable author statement PubMed 12464307. Source: FlyBase

glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity

Inferred from sequence or structural similarity. Source: UniProtKB

glucuronosyltransferase activity

Non-traceable author statement PubMed 12464307. Source: FlyBase

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Ext2Q9Y1693EBI-166374,EBI-142791

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 760760Exostosin-1
PRO_0000149664

Regions

Topological domain1 – 66Cytoplasmic Potential
Transmembrane7 – 2519Helical; Signal-anchor for type II membrane protein; Potential
Topological domain26 – 760735Lumenal Potential

Amino acid modifications

Glycosylation711N-linked (GlcNAc...) Potential
Glycosylation3271N-linked (GlcNAc...) Potential
Glycosylation4761N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis4471G → D in ttv205; induces defects in wing patterning due to impaired movement of morphogens. Ref.10

Sequences

Sequence LengthMass (Da)Tools
Q9V730 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: F6369F0BA206DEA9

FASTA76087,309
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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, DISRUPTION PHENOTYPE, MUTAGENESIS OF GLY-447.
[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.
[14]"The Drosophila GOLPH3 homolog regulates the biosynthesis of heparan sulfate proteoglycans by modulating the retrograde trafficking of exostosins."
Chang W.L., Chang C.W., Chang Y.Y., Sung H.H., Lin M.D., Chang S.C., Chen C.H., Huang C.W., Tung K.S., Chou T.B.
Development 140:2798-2807(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RTI, SUBCELLULAR LOCATION.
+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.
RefSeqNP_001260971.1. NM_001274042.1.
NP_477231.1. NM_057883.3.
UniGeneDm.2966.

3D structure databases

ProteinModelPortalQ9V730.
SMRQ9V730. Positions 475-749.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid62362. 2 interactions.
IntActQ9V730. 4 interactions.
MINTMINT-7953341.

Protein family/group databases

CAZyGT47. Glycosyltransferase Family 47.
GT64. Glycosyltransferase Family 64.

Proteomic databases

PaxDbQ9V730.
PRIDEQ9V730.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaFBtr0087495; FBpp0086624; FBgn0020245.
FBtr0333164; FBpp0305367; FBgn0020245.
GeneID36614.
KEGGdme:Dmel_CG10117.

Organism-specific databases

CTD36614.
FlyBaseFBgn0265974. ttv.

Phylogenomic databases

eggNOGNOG272619.
GeneTreeENSGT00550000074496.
InParanoidQ5BI21.
KOK02366.
OMAWEAYFNS.
PhylomeDBQ9V730.

Enzyme and pathway databases

SignaLinkQ9V730.
UniPathwayUPA00378.
UPA00756.
UPA00862.

Gene expression databases

BgeeQ9V730.

Family and domain databases

InterProIPR004263. Exostosin.
IPR027670. Exostosin-1.
IPR015338. HexNAc_Trfase_a.
[Graphical view]
PANTHERPTHR11062. PTHR11062. 1 hit.
PTHR11062:SF7. PTHR11062:SF7. 1 hit.
PfamPF03016. Exostosin. 1 hit.
PF09258. Glyco_transf_64. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSEXT1. drosophila.
GenomeRNAi36614.
NextBio799500.
PROQ9V730.

Entry information

Entry nameEXT1_DROME
AccessionPrimary (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: April 16, 2014
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

Drosophila

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