Reviewed, UniProtKB/Swiss-Prot Q9Y169 (EXT2_DROME)

Names and origin

Protein names

Recommended name:
    Exostosin-2
    EC=2.4.1.224
    EC=2.4.1.225
Alternative name(s):
    Protein sister of tout-velu

Gene names

Name:	Ext2
Synonyms:	DEXT2, sotv
ORF Names:	CG33038

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	717 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->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. 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.
Pathway	Protein modification; protein glycosylation. Glycan metabolism; heparan sulfate biosynthesis. Glycan metabolism; heparin biosynthesis.
Subunit structure	Forms a homo/hetero-oligomeric complex with ttv Probable.
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 both maternally and zygotically. Ref.7
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 Ref.7 Inferred from mutant phenotype. Source: UniProtKB chondroitin sulfate biosynthetic process Ref.7 Inferred from mutant phenotype. Source: FlyBase decapentaplegic receptor signaling pathway Ref.5 Ref.6 Ref.7 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.7 Inferred from mutant phenotype. Source: FlyBase multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW smoothened signaling pathway Ref.5 Ref.6 Ref.7 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	Golgi apparatus Ref.6 Inferred from direct assay. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell 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.6 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	Q9VMY9	1	EBI-142791,EBI-151773
ttv	Q9V730	1	EBI-142791,EBI-166374

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 717	717	Exostosin-2		PRO_0000149665
Regions
	Topological domain	1 – 25	25	Cytoplasmic Potential
	Transmembrane	26 – 46	21	Signal-anchor for type II membrane protein Potential
	Topological domain	47 – 717	671	Lumenal Potential
Amino acid modifications
	Glycosylation	91	1	N-linked (GlcNAc...) Potential
	Glycosylation	574	1	N-linked (GlcNAc...) Potential
	Glycosylation	636	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	Q9Y169-1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: A3894493C16EF7DC	FASTA	717	82,726
	10 20 30 40 50 60 MTKIKNLLSF VTQSRAISHT NPREHILNCL TYGLLVIVAL CAGFLLWDLS SSPRDGFFHG 70 80 90 100 110 120 KRDSHTLILD LEHIQELAVN PEAEQRARNV NCTFWDCLNI YKCEHDRLKV YIYPLQEFVD 130 140 150 160 170 180 EQSDKTATTL SSEYFQILEA VLKSRYYTSN PNEACLFLPS LDLLNQNVFD KHLAGAALAS 190 200 210 220 230 240 LDFWDRGANH IIFNMLPGGA PSYNTVLDVN TDNAIIFGGG FDSWSYRPGF DVAIPVWSPR 250 260 270 280 290 300 LVRQHAHATA QRKFLLVVAQ LNILPRFVRT LRELSLAHSE QLLLLGACEN LDLTMRCPLS 310 320 330 340 350 360 QHHKSLEYPR LLSRGKFCLL GRSLRMGQPD LVEIMSQHCI PVIAVDNYVL PFEDVIDWSL 370 380 390 400 410 420 ASVRIRENEL HSVMQKLKAI SSVKIVEMQK QVQWLFSKYF KDLKTVTLTA LEVLESRIFP 430 440 450 460 470 480 LRARSSRQWN TIDTNARSTF NPLFLPSLAP KSQGFTAVIL TYDRVESLFL LIQKLAVVPS 490 500 510 520 530 540 LQSILVIWNN QKKSPPHLST FPSISKPLKI RQTKENKLSN RFYPYPEIET EAILTIDDDI 550 560 570 580 590 600 IMLTTDELDF GYEVWREFPD HIVGFPSRIH VWENVTMRWH YESEWTNQIS MVLTGAAFHH 610 620 630 640 650 660 KYWSHMYTHA MPGDIKDWVD EHMNCEDIAM NFLVANITNN PPIKVTPRKK FKCPECTNTE 670 680 690 700 710 MLSADLNHMR ERSACIDRFS KIYGRMPLRT VEFRADPVLF RDNFPDKLKR YNDIGSL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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.
[2]	"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.
[3]	"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: Head.
[4]	Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M., Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A., Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A. , Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S., Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Berkeley. Tissue: Head.
[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.
[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.
[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, DEVELOPMENTAL STAGE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AE013599 Genomic DNA. Translation: AAF58055.2. AF145598 mRNA. Translation: AAD38573.1. BT003544 mRNA. Translation: AAO39548.1.
RefSeq	NP_725536.1. NP_725537.2.
UniGene	Dm.20855
3D structure databases
SMR	Q9Y169. Positions 453-700.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y169. 3 interactions.
STRING	Q9Y169.
Protein family/group databases
CAZy	GT47. Glycosyltransferase Family 47. GT64. Glycosyltransferase Family 64.
Proteomic databases
PRIDE	Q9Y169.
Genome annotation databases
Ensembl	FBtr0100512; FBpp0099952; FBgn0029175; Drosophila melanogaster. [Genome view] FBtr0100513; FBpp0099953; FBgn0029175; Drosophila melanogaster. [Genome view]
GeneID	3772101.
KEGG	dme:Dmel_CG8433.
Organism-specific databases
CTD	3772101.
FlyBase	FBgn0029175. Ext2.
Phylogenomic databases
eggNOG	inNOG07969.
InParanoid	Q9Y169.
OMA	QMALHPE.
OrthoDB	EOG94QT6V.
PhylomeDB	Q9Y169.
Enzyme and pathway databases
BRENDA	2.4.1.224. 48. 2.4.1.225. 48.
Gene expression databases
GermOnline	CG8433. 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	852446.

Entry information

Entry name

EXT2_DROME

Accession

Primary (citable) accession number: Q9Y169

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	November 1, 1999
Last modified:	January 19, 2010
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project