EXT3_DROME
ID EXT3_DROME Reviewed; 972 AA.
AC Q9XZ08;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Exostosin-3;
DE EC=2.4.1.223 {ECO:0000269|PubMed:11832488};
DE AltName: Full=Protein brother of tout-velu;
GN Name=botv; Synonyms=DEXT3; ORFNames=CG15110;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Embryo;
RX PubMed=11832488; DOI=10.1074/jbc.m111630200;
RA Kim B.-T., Kitagawa H., Tamura J., Kusche-Gullberg M., Lindahl U.,
RA Sugahara K.;
RT "Demonstration of a novel gene DEXT3 of Drosophila melanogaster as the
RT essential N-acetylglucosamine transferase in the heparan sulfate
RT biosynthesis: chain initiation and elongation.";
RL J. Biol. Chem. 277:13659-13665(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=10731138; DOI=10.1126/science.287.5461.2222;
RA Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M.,
RA Harvey D.A.;
RT "A Drosophila complementary DNA resource.";
RL Science 287:2222-2224(2000).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF PRO-669 AND GLY-821.
RX PubMed=14645127; DOI=10.1242/dev.00913;
RA Takei Y., Ozawa Y., Sato M., Watanabe A., Tabata T.;
RT "Three Drosophila EXT genes shape morphogen gradients through synthesis of
RT heparan sulfate proteoglycans.";
RL Development 131:73-82(2004).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF GLY-707.
RX PubMed=14998928; DOI=10.1242/dev.01051;
RA Han C., Belenkaya T.Y., Khodoun M., Tauchi M., Lin X., Lin X.;
RT "Distinct and collaborative roles of Drosophila EXT family proteins in
RT morphogen signalling and gradient formation.";
RL Development 131:1563-1575(2004).
RN [7]
RP FUNCTION.
RX PubMed=15056609; DOI=10.1242/dev.01061;
RA Bornemann D.J., Duncan J.E., Staatz W., Selleck S., Warrior R.;
RT "Abrogation of heparan sulfate synthesis in Drosophila disrupts the
RT Wingless, Hedgehog and Decapentaplegic signaling pathways.";
RL Development 131:1927-1938(2004).
RN [8]
RP INTERACTION WITH SAU, AND SUBCELLULAR LOCATION.
RX PubMed=23720043; DOI=10.1242/dev.087171;
RA Chang W.L., Chang C.W., Chang Y.Y., Sung H.H., Lin M.D., Chang S.C.,
RA Chen C.H., Huang C.W., Tung K.S., Chou T.B.;
RT "The Drosophila GOLPH3 homolog regulates the biosynthesis of heparan
RT sulfate proteoglycans by modulating the retrograde trafficking of
RT exostosins.";
RL Development 140:2798-2807(2013).
CC -!- FUNCTION: Glycosyltransferase required for the biosynthesis of heparan-
CC sulfate and responsible for the alternating addition of beta-1-4-linked
CC glucuronic acid (GlcA) and alpha-1-4-linked N-acetylglucosamine
CC (GlcNAc) units to nascent heparan sulfate chains. Plays a central role
CC in diffusion of morphogens hedgehog (hh), wingless (wg) and
CC Decapentaplegic (dpp) via its role in heparan sulfate proteoglycans
CC (HSPGs) biosynthesis, HSPGs being required for movement of Hh, Dpp and
CC wg morphogens. {ECO:0000269|PubMed:14645127,
CC ECO:0000269|PubMed:14998928, ECO:0000269|PubMed:15056609}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-(beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-
CC beta-D-Xyl)-L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-
CC O-(alpha-D-GlcNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-
CC Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + H(+) + UDP;
CC Xref=Rhea:RHEA:16221, Rhea:RHEA-COMP:12573, Rhea:RHEA-COMP:12574,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:132093, ChEBI:CHEBI:132104; EC=2.4.1.223;
CC Evidence={ECO:0000269|PubMed:11832488};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9ES89};
CC -!- PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
CC -!- SUBUNIT: Interacts with sau. {ECO:0000269|PubMed:23720043}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Single-pass type II membrane protein {ECO:0000250}. Golgi apparatus
CC membrane {ECO:0000269|PubMed:23720043}; Single-pass type II membrane
CC protein {ECO:0000269|PubMed:23720043}. Note=Localization to the Golgi
CC may be regulated by sau (PubMed:23720043).
CC -!- TISSUE SPECIFICITY: In wing imaginal disk, it is ubiquitously
CC expressed. {ECO:0000269|PubMed:14645127}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout the developmental stages in
CC both head and body from males and females.
CC {ECO:0000269|PubMed:11832488}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 47 family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB077850; BAB89399.1; -; mRNA.
DR EMBL; AE013599; AAF57601.1; -; Genomic_DNA.
DR EMBL; AF132161; AAD34749.1; -; mRNA.
DR RefSeq; NP_523790.1; NM_079066.3.
DR AlphaFoldDB; Q9XZ08; -.
DR SMR; Q9XZ08; -.
DR BioGRID; 62863; 7.
DR IntAct; Q9XZ08; 1.
DR STRING; 7227.FBpp0085763; -.
DR CAZy; GT47; Glycosyltransferase Family 47.
DR CAZy; GT64; Glycosyltransferase Family 64.
DR GlyGen; Q9XZ08; 4 sites.
DR PaxDb; Q9XZ08; -.
DR PRIDE; Q9XZ08; -.
DR DNASU; 37198; -.
DR EnsemblMetazoa; FBtr0086579; FBpp0085763; FBgn0027535.
DR GeneID; 37198; -.
DR KEGG; dme:Dmel_CG15110; -.
DR CTD; 37198; -.
DR FlyBase; FBgn0027535; botv.
DR VEuPathDB; VectorBase:FBgn0027535; -.
DR eggNOG; KOG2264; Eukaryota.
DR GeneTree; ENSGT00940000156692; -.
DR HOGENOM; CLU_013906_3_0_1; -.
DR InParanoid; Q9XZ08; -.
DR OMA; AKFMGSH; -.
DR OrthoDB; 789556at2759; -.
DR PhylomeDB; Q9XZ08; -.
DR BRENDA; 2.4.1.223; 1994.
DR BRENDA; 2.4.1.224; 1994.
DR SignaLink; Q9XZ08; -.
DR UniPathway; UPA00756; -.
DR BioGRID-ORCS; 37198; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 37198; -.
DR PRO; PR:Q9XZ08; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0027535; Expressed in embryonic/larval hemocyte (Drosophila) and 27 other tissues.
DR Genevisible; Q9XZ08; DM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISM:FlyBase.
DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; IDA:UniProtKB.
DR GO; GO:0001888; F:glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity; IDA:FlyBase.
DR GO; GO:0016757; F:glycosyltransferase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; IMP:FlyBase.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IDA:FlyBase.
DR GO; GO:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; IMP:FlyBase.
DR GO; GO:0030201; P:heparan sulfate proteoglycan metabolic process; IMP:FlyBase.
DR GO; GO:0030210; P:heparin biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; ISS:UniProtKB.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IMP:UniProtKB.
DR GO; GO:0006486; P:protein glycosylation; IEA:InterPro.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR004263; Exostosin.
DR InterPro; IPR040911; Exostosin_GT47.
DR InterPro; IPR015338; GT64.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR11062; PTHR11062; 1.
DR Pfam; PF03016; Exostosin; 1.
DR Pfam; PF09258; Glyco_transf_64; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Glycosyltransferase; Golgi apparatus; Manganese; Membrane; Metal-binding;
KW Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix; Wnt signaling pathway.
FT CHAIN 1..972
FT /note="Exostosin-3"
FT /id="PRO_0000149666"
FT TOPO_DOM 1..55
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..76
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 77..972
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 886
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 748
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 774..779
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 795..797
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 797
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 825
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 882..886
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT CARBOHYD 218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 606
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 643
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 843
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 884..932
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT MUTAGEN 669
FT /note="P->L: In botv510; induces defects in wing patterning
FT due to impaired movement of morphogens."
FT /evidence="ECO:0000269|PubMed:14645127"
FT MUTAGEN 707
FT /note="G->D: In botv8; induces defects in wing patterning
FT due to impaired movement of morphogens."
FT /evidence="ECO:0000269|PubMed:14998928"
FT MUTAGEN 821
FT /note="G->D: In botv514; induces defects in wing patterning
FT due to impaired movement of morphogens."
FT /evidence="ECO:0000269|PubMed:14645127"
SQ SEQUENCE 972 AA; 111000 MW; 2A111BD6912FFCCA CRC64;
MPPAYDLGHS GEAYQPLDTG SGGGNEACAP NSSSAQIRHS MGFRTSWMRQ FRRYKLPMVL
LMLLFLVSCL AYRILSVEQD APPLDLHRSS PLLDAYEDFS AMRAGDLKMR IEEMVRIKST
VSVELRELES RRQKLQSDIS QYNQKIEELK QELLREQTEL ERLKISVEQA QVAQREAVQR
NTPDLALPRS LLPNTLPRKS NPITGGMAAS CEMHNCFNHS RCSLTSGFPV YLYDPDEHSV
QRKGYDIDGF LKTTLKQTLG YNAHIVKDPK HACIYLVLVG EALLEQDLLR NNRYAAQEAE
HQQPSTPTLE NDCPVDMEKL YSLPYWGGDG RNHVLLNLAR RDLTSHRTNP LYRQNTMRAI
VVQSAFEREQ FRPGYDLIVP PILGPPGGDV WQECAEMVPA RRKYLLTYQG ELRPKQSSLN
PLDAFILEHL ADMAKGATQD QFVLQFQCVP ATEQQEGDSL PDWTLCGSDS SRRQLLKDST
FSLILPPLNG RVSSTLMLAR IYEALRSGAV PVILGADELR LPYAETVDWR RTALLLPKAR
ITELHFLLRA VQDADLLLLR RQGRLIWERY LSSVQATVDT VIASLRDRLG IPPRPVPSVI
AQSVFNSTFI PLKSDPPVGL DTEPEESLGP IEPPYPSPAF RRNYTILRMQ AKEAWNDWLD
PFYLYPQLPF DPALPSEAKF MGSHTGFRPI GKGLGGAGKE FGESLGGNYP REQFTIVMLT
YEREQVLMDS LGRLYGLPYL HKVVVVWNSP KPPLDDLRWP DIGVPVAVLR APRNSLNNRF
LPFDVIETEA VLSVDDDAHL RHDEILFGFR VWREHRDRVV GFPGRYHAWD LGNPNGQWHY
NSNYSCELSM VLTGAAFVHK YYLYLYTYHL PQAIRDKVDE YMNCEDIAMN FLVSHITRKP
PVKVTSRWTF RCPGCPVSLS EDDTHFQERH KCINFFSRVF GYTPLLNTQY RADSILFKTR
IPHDKQKCFK YI
