EXT2_DROME
ID EXT2_DROME Reviewed; 717 AA.
AC Q9Y169; A4UZJ2;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Exostosin-2;
DE EC=2.4.1.224;
DE EC=2.4.1.225;
DE AltName: Full=Protein sister of tout-velu;
GN Name=sotv {ECO:0000303|PubMed:15056609, ECO:0000312|FlyBase:FBgn0029175};
GN Synonyms=Ext2 {ECO:0000312|FlyBase:FBgn0029175};
GN ORFNames=CG33038 {ECO:0000312|FlyBase:FBgn0029175};
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 [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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
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.
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, AND DEVELOPMENTAL STAGE.
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-{[(1->4)-beta-D-GlcA-(1->4)-alpha-D-GlcNAc](n)-(1->4)-
CC beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl}-L-
CC seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-{alpha-D-
CC GlcNAc-[(1->4)-beta-D-GlcA-(1->4)-alpha-D-GlcNAc](n)-(1->4)-beta-D-
CC GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl}-L-seryl-
CC [protein] + H(+) + UDP; Xref=Rhea:RHEA:16213, Rhea:RHEA-COMP:12621,
CC Rhea:RHEA-COMP:12623, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:132415, ChEBI:CHEBI:132416;
CC EC=2.4.1.224;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-{alpha-D-GlcNAc-[(1->4)-beta-D-GlcA-(1->4)-alpha-D-
CC GlcNAc](n)-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-
CC (1->4)-beta-D-Xyl}-L-seryl-[protein] + UDP-alpha-D-glucuronate = 3-
CC O-{[(1->4)-beta-D-GlcA-(1->4)-alpha-D-GlcNAc](n+1)-(1->4)-beta-D-
CC GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl}-L-seryl-
CC [protein] + H(+) + UDP; Xref=Rhea:RHEA:20908, Rhea:RHEA-COMP:12623,
CC Rhea:RHEA-COMP:14295, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:132415, ChEBI:CHEBI:132416;
CC EC=2.4.1.225;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9ES89};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
CC -!- PATHWAY: Glycan metabolism; heparin biosynthesis.
CC -!- SUBUNIT: Interacts with sau. {ECO:0000269|PubMed:23720043}.
CC -!- INTERACTION:
CC Q9Y169; Q9V730: ttv; NbExp=3; IntAct=EBI-142791, EBI-166374;
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 both maternally and zygotically.
CC {ECO:0000269|PubMed:15056609}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 47 family.
CC {ECO:0000305}.
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DR EMBL; AE013599; AAO41379.1; -; Genomic_DNA.
DR EMBL; AF145598; AAD38573.1; -; mRNA.
DR EMBL; BT003544; AAO39548.1; -; mRNA.
DR RefSeq; NP_725536.1; NM_166150.3.
DR AlphaFoldDB; Q9Y169; -.
DR SMR; Q9Y169; -.
DR BioGRID; 533698; 4.
DR IntAct; Q9Y169; 2.
DR STRING; 7227.FBpp0099952; -.
DR CAZy; GT47; Glycosyltransferase Family 47.
DR CAZy; GT64; Glycosyltransferase Family 64.
DR GlyGen; Q9Y169; 3 sites.
DR PaxDb; Q9Y169; -.
DR EnsemblMetazoa; FBtr0100513; FBpp0099953; FBgn0029175.
DR GeneID; 3772101; -.
DR KEGG; dme:Dmel_CG8433; -.
DR UCSC; CG8433-RB; d. melanogaster.
DR CTD; 3772101; -.
DR FlyBase; FBgn0029175; sotv.
DR VEuPathDB; VectorBase:FBgn0029175; -.
DR eggNOG; KOG1022; Eukaryota.
DR GeneTree; ENSGT00940000156620; -.
DR HOGENOM; CLU_013906_4_1_1; -.
DR InParanoid; Q9Y169; -.
DR OMA; NCTFWDC; -.
DR OrthoDB; 789556at2759; -.
DR PhylomeDB; Q9Y169; -.
DR BRENDA; 2.4.1.224; 1994.
DR BRENDA; 2.4.1.225; 1994.
DR Reactome; R-DME-2022928; HS-GAG biosynthesis.
DR SignaLink; Q9Y169; -.
DR UniPathway; UPA00378; -.
DR UniPathway; UPA00756; -.
DR UniPathway; UPA00862; -.
DR BioGRID-ORCS; 3772101; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 3772101; -.
DR PRO; PR:Q9Y169; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0029175; Expressed in second segment of antenna (Drosophila) and 23 other tissues.
DR Genevisible; Q9Y169; 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; IEA:UniProtKB-KW.
DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; IDA:FlyBase.
DR GO; GO:0050508; F:glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity; ISS:UniProtKB.
DR GO; GO:0016757; F:glycosyltransferase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050509; F:N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity; IDA:FlyBase.
DR GO; GO:0030206; P:chondroitin sulfate biosynthetic process; IMP:FlyBase.
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:0030210; P:heparin biosynthetic process; IMP:FlyBase.
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:UniProtKB-UniPathway.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR004263; Exostosin.
DR InterPro; IPR027673; Exostosin-2.
DR InterPro; IPR040911; Exostosin_GT47.
DR InterPro; IPR015338; GT64.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR11062; PTHR11062; 1.
DR PANTHER; PTHR11062:SF128; PTHR11062:SF128; 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..717
FT /note="Exostosin-2"
FT /id="PRO_0000149665"
FT TOPO_DOM 1..25
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 26..46
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 47..717
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 627
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 489
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 516..521
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 537..539
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 539
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 568
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 623..627
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 661..672
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 574
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 636
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 625..675
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
SQ SEQUENCE 717 AA; 82726 MW; A3894493C16EF7DC CRC64;
MTKIKNLLSF VTQSRAISHT NPREHILNCL TYGLLVIVAL CAGFLLWDLS SSPRDGFFHG
KRDSHTLILD LEHIQELAVN PEAEQRARNV NCTFWDCLNI YKCEHDRLKV YIYPLQEFVD
EQSDKTATTL SSEYFQILEA VLKSRYYTSN PNEACLFLPS LDLLNQNVFD KHLAGAALAS
LDFWDRGANH IIFNMLPGGA PSYNTVLDVN TDNAIIFGGG FDSWSYRPGF DVAIPVWSPR
LVRQHAHATA QRKFLLVVAQ LNILPRFVRT LRELSLAHSE QLLLLGACEN LDLTMRCPLS
QHHKSLEYPR LLSRGKFCLL GRSLRMGQPD LVEIMSQHCI PVIAVDNYVL PFEDVIDWSL
ASVRIRENEL HSVMQKLKAI SSVKIVEMQK QVQWLFSKYF KDLKTVTLTA LEVLESRIFP
LRARSSRQWN TIDTNARSTF NPLFLPSLAP KSQGFTAVIL TYDRVESLFL LIQKLAVVPS
LQSILVIWNN QKKSPPHLST FPSISKPLKI RQTKENKLSN RFYPYPEIET EAILTIDDDI
IMLTTDELDF GYEVWREFPD HIVGFPSRIH VWENVTMRWH YESEWTNQIS MVLTGAAFHH
KYWSHMYTHA MPGDIKDWVD EHMNCEDIAM NFLVANITNN PPIKVTPRKK FKCPECTNTE
MLSADLNHMR ERSACIDRFS KIYGRMPLRT VEFRADPVLF RDNFPDKLKR YNDIGSL
