EXT2_HUMAN
ID EXT2_HUMAN Reviewed; 718 AA.
AC Q93063; B2R5Z6; C9JU51; J3KPT2; O15288;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Exostosin-2;
DE EC=2.4.1.224;
DE EC=2.4.1.225;
DE AltName: Full=Glucuronosyl-N-acetylglucosaminyl-proteoglycan/N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase;
DE AltName: Full=Multiple exostoses protein 2;
DE AltName: Full=Putative tumor suppressor protein EXT2;
GN Name=EXT2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8782816; DOI=10.1038/ng0996-25;
RA Stickens D.J., Clines G., Burbee D.G., Ramos P., Thomas S., Hogue D.,
RA Hecht J.T., Lovett M., Evans G.A.;
RT "The EXT2 multiple exostoses gene defines a family of putative tumour
RT suppressor genes.";
RL Nat. Genet. 14:25-32(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8894688; DOI=10.1093/hmg/5.10.1547;
RA Wuyts W., van Hul W., Wauters J., Nemtsova M., Reyniers E., van Hul E.,
RA de Boulle K., de Vries B.B.A., Hendrickx J., Herrygers I., Bossuyt P.,
RA Balemans W., Fransen E., Vits L., Coucke P., Nowak N.J., Mallet L.,
RA van den Ouweland A.M.W., McGaughran J., Halley D.J.J., Willems P.J.;
RT "Positional cloning of a gene involved in hereditary multiple exostoses.";
RL Hum. Mol. Genet. 5:1547-1557(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=9110175; DOI=10.1101/gr.7.4.359;
RA Clines G.A., Ashley J.A., Shah S., Lovett M.;
RT "The structure of the human multiple exostoses 2 gene and characterization
RT of homologs in mouse and Caenorhabditis elegans.";
RL Genome Res. 7:359-367(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
RA Deng H.-X., Fan C., Xia J.H., Xu L., He X.X., Ruan Q.G., Yang Y., Huang L.;
RT "Molecular cloning of a candidate gene for hereditary multiple exostoses
RT type II.";
RL Prog. Nat. Sci. 6:692-699(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Endometrial cancer;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=10679296; DOI=10.1006/bbrc.2000.2219;
RA Kobayashi S., Morimoto K., Shimizu T., Takahashi M., Kurosawa H.,
RA Shirasawa T.;
RT "Association of EXT1 and EXT2, hereditary multiple exostoses gene products,
RT in Golgi apparatus.";
RL Biochem. Biophys. Res. Commun. 268:860-867(2000).
RN [11]
RP INTERACTION WITH GALNT5.
RX PubMed=10545594; DOI=10.1093/hmg/8.12.2155;
RA Simmons A.D., Musy M.M., Lopes C.S., Hwang L.-Y., Yang Y.-P., Lovett M.;
RT "A direct interaction between EXT proteins and glycosyltransferases is
RT defective in hereditary multiple exostoses.";
RL Hum. Mol. Genet. 8:2155-2164(1999).
RN [12]
RP REVIEW ON VARIANTS.
RX PubMed=10679937;
RX DOI=10.1002/(sici)1098-1004(200003)15:3<220::aid-humu2>3.0.co;2-k;
RA Wuyts W., Van Hul W.;
RT "Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2
RT genes.";
RL Hum. Mutat. 15:220-227(2000).
RN [13]
RP INTERACTION WITH NDST1.
RX PubMed=18337501; DOI=10.1073/pnas.0705807105;
RA Presto J., Thuveson M., Carlsson P., Busse M., Wilen M., Eriksson I.,
RA Kusche-Gullberg M., Kjellen L.;
RT "Heparan sulfate biosynthesis enzymes EXT1 and EXT2 affect NDST1 expression
RT and heparan sulfate sulfation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:4751-4756(2008).
RN [14]
RP FUNCTION.
RX PubMed=22660413; DOI=10.1038/ncb2502;
RA Baietti M.F., Zhang Z., Mortier E., Melchior A., Degeest G., Geeraerts A.,
RA Ivarsson Y., Depoortere F., Coomans C., Vermeiren E., Zimmermann P.,
RA David G.;
RT "Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.";
RL Nat. Cell Biol. 14:677-685(2012).
RN [15]
RP INTERACTION WITH NDST1, AND SUBCELLULAR LOCATION.
RX PubMed=35137078; DOI=10.1093/glycob/cwac004;
RA Missaghian P., Dierker T., Khosrowabadi E., Axling F., Eriksson I.,
RA Ghanem A., Kusche-Gullberg M., Kellokumpu S., Kjellen L.;
RT "A dominant negative splice variant of the heparan sulfate biosynthesis
RT enzyme NDST1 reduces heparan sulfate sulfation.";
RL Glycobiology 0:0-0(2022).
RN [16]
RP INVOLVEMENT IN SSMS, VARIANTS SSMS ARG-87 AND CYS-95, AND CHARACTERIZATION
RP OF VARIANTS SSMS ARG-87 AND CYS-95.
RX PubMed=26246518; DOI=10.1136/jmedgenet-2015-103279;
RG FORGE Canada Consortium;
RA Farhan S.M., Wang J., Robinson J.F., Prasad A.N., Rupar C.A., Siu V.M.,
RA Hegele R.A.;
RT "Old gene, new phenotype: mutations in heparan sulfate synthesis enzyme,
RT EXT2 leads to seizure and developmental disorder, no exostoses.";
RL J. Med. Genet. 52:666-675(2015).
RN [17]
RP VARIANT EXT2 ASN-227.
RX PubMed=9326317; DOI=10.1086/515505;
RA Philippe C., Porter D.E., Emerton M.E., Wells D.E., Simpson A.H.R.W.,
RA Monaco A.P.;
RT "Mutation screening of the EXT1 and EXT2 genes in patients with hereditary
RT multiple exostoses.";
RL Am. J. Hum. Genet. 61:520-528(1997).
RN [18]
RP VARIANT EXT2 ARG-152, AND ALTERNATIVE SPLICING.
RX PubMed=10480354; DOI=10.1007/s004399900058;
RA Xu L., Xia J., Jiang H., Zhou J., Li H., Wang D., Pan Q., Long Z., Fan C.,
RA Deng H.-X.;
RT "Mutation analysis of hereditary multiple exostoses in the Chinese.";
RL Hum. Genet. 105:45-50(1999).
RN [19]
RP VARIANT EXT2 ARG-85.
RX PubMed=10429361; DOI=10.1007/s100380050149;
RA Park K.J., Shin K.-H., Ku J.-L., Cho T.-J., Lee S.H., Choi I.H.,
RA Philippe C., Monaco A.P., Porter D.E., Park J.-G.;
RT "Germline mutations in the EXT1 and EXT2 genes in Korean patients with
RT hereditary multiple exostoses.";
RL J. Hum. Genet. 44:230-234(1999).
RN [20]
RP VARIANT EXT2 PRO-223.
RX PubMed=10738008;
RX DOI=10.1002/(sici)1098-1004(200004)15:4<390::aid-humu35>3.0.co;2-e;
RA Shi Y.-R., Wu J.-Y., Tsai F.-J., Lee C.-C., Tsai C.-H.;
RT "An R223P mutation in EXT2 gene causes hereditary multiple exostoses.";
RL Hum. Mutat. 15:390-391(2000).
RN [21]
RP VARIANT EXT2 VAL-202.
RX PubMed=11170095;
RX DOI=10.1002/1096-8628(20010215)99:1<59::aid-ajmg1115>3.0.co;2-z;
RA Seki H., Kubota T., Ikegawa S., Haga N., Fujioka F., Ohzeki S., Wakui K.,
RA Yoshikawa H., Takaoka K., Fukushima Y.;
RT "Mutation frequencies of EXT1 and EXT2 in 43 Japanese families with
RT hereditary multiple exostoses.";
RL Am. J. Med. Genet. 99:59-62(2001).
RN [22]
RP VARIANT EXT2 ASN-227.
RX PubMed=11169766;
RX DOI=10.1002/1097-0169(200102)48:2<149::aid-cm1005>3.0.co;2-3;
RA Bernard M.A., Hall C.E., Hogue D.A., Cole W.G., Scott A., Snuggs M.B.,
RA Clines G.A., Luedecke H.-J., Lovett M., Van Winkle W.B., Hecht J.T.;
RT "Diminished levels of the putative tumor suppressor proteins EXT1 and EXT2
RT in exostosis chondrocytes.";
RL Cell Motil. Cytoskeleton 48:149-162(2001).
RN [23]
RP VARIANT EXT2 THR-380, AND VARIANT OSTEOCHONDROMA LYS-576.
RX PubMed=11668521;
RX DOI=10.1002/1097-0215(20011120)95:6<378::aid-ijc1067>3.0.co;2-f;
RA Gigante M., Matera M.G., Seripa D., Izzo A.M., Venanzi R., Giannotti A.,
RA Digilio M.C., Gravina C., Lazzari M., Monteleone G., Monteleone M.,
RA Dallapiccola B., Fazio V.M.;
RT "Ext-mutation analysis in Italian sporadic and hereditary
RT osteochondromas.";
RL Int. J. Cancer 95:378-383(2001).
RN [24]
RP VARIANTS EXT2 SER-179 AND ASN-227.
RX PubMed=11432960; DOI=10.1136/jmg.38.7.430;
RA Francannet C., Cohen-Tanugi A., Le Merrer M., Munnich A., Bonaventure J.,
RA Legeai-Mallet L.;
RT "Genotype-phenotype correlation in hereditary multiple exostoses.";
RL J. Med. Genet. 38:430-434(2001).
RN [25]
RP VARIANT EXT2 ASN-227.
RX PubMed=19344451; DOI=10.1111/j.1469-1809.2009.00508.x;
RA Heinritz W., Hueffmeier U., Strenge S., Miterski B., Zweier C., Leinung S.,
RA Bohring A., Mitulla B., Peters U., Froster U.G.;
RT "New mutations of EXT1 and EXT2 genes in German patients with Multiple
RT Osteochondromas.";
RL Ann. Hum. Genet. 73:283-291(2009).
CC -!- FUNCTION: Glycosyltransferase required for the biosynthesis of heparan-
CC sulfate. The EXT1/EXT2 complex possesses substantially higher
CC glycosyltransferase activity than EXT1 or EXT2 alone. Appears to be a
CC tumor suppressor. Required for the exosomal release of SDCBP, CD63 and
CC syndecan (PubMed:22660413). {ECO:0000269|PubMed:22660413}.
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 -!- SUBUNIT: Forms a homo/heterooligomeric complex with EXT1. Interacts
CC with GALNT5. Interacts with NDST1. {ECO:0000269|PubMed:10545594,
CC ECO:0000269|PubMed:10679296, ECO:0000269|PubMed:18337501,
CC ECO:0000269|PubMed:35137078}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10679296}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:10679296}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:10679296}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:10679296}. Golgi apparatus, cis-Golgi network
CC membrane {ECO:0000269|PubMed:35137078}; Single-pass type II membrane
CC protein {ECO:0000255}. Note=The EXT1/EXT2 complex is localized in the
CC Golgi apparatus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q93063-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q93063-2; Sequence=VSP_001798;
CC Name=3;
CC IsoId=Q93063-3; Sequence=VSP_046053;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DISEASE: Hereditary multiple exostoses 2 (EXT2) [MIM:133701]: EXT is a
CC genetically heterogeneous bone disorder caused by genes segregating on
CC human chromosomes 8, 11, and 19 and designated EXT1, EXT2 and EXT3
CC respectively. EXT is a dominantly inherited skeletal disorder primarily
CC affecting endochondral bone during growth. The disease is characterized
CC by formation of numerous cartilage-capped, benign bone tumors
CC (osteocartilaginous exostoses or osteochondromas) that are often
CC accompanied by skeletal deformities and short stature. In a small
CC percentage of cases exostoses have exhibited malignant transformation
CC resulting in an osteosarcoma or chondrosarcoma. Osteochondromas
CC development can also occur as a sporadic event.
CC {ECO:0000269|PubMed:10429361, ECO:0000269|PubMed:10480354,
CC ECO:0000269|PubMed:10738008, ECO:0000269|PubMed:11169766,
CC ECO:0000269|PubMed:11170095, ECO:0000269|PubMed:11432960,
CC ECO:0000269|PubMed:11668521, ECO:0000269|PubMed:19344451,
CC ECO:0000269|PubMed:9326317}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Potocki-Shaffer syndrome (POSHS) [MIM:601224]: A syndrome
CC characterized by foramina parietalia permagna, multiple exostoses, and
CC craniofacial dysostosis, and intellectual disability in some cases.
CC Note=The gene represented in this entry is involved in disease
CC pathogenesis.
CC -!- DISEASE: Seizures, scoliosis, and macrocephaly/microcephaly syndrome
CC (SSMS) [MIM:616682]: An autosomal recessive syndrome characterized by
CC seizures, intellectual disability, hypotonia, scoliosis, macrocephaly,
CC hypertelorism and renal dysfunction. {ECO:0000269|PubMed:26246518}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 47 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/EXT2ID213.html";
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DR EMBL; U62740; AAB07008.1; -; mRNA.
DR EMBL; U64511; AAC50764.1; -; mRNA.
DR EMBL; U67368; AAC51219.1; -; Genomic_DNA.
DR EMBL; U67356; AAC51219.1; JOINED; Genomic_DNA.
DR EMBL; U67357; AAC51219.1; JOINED; Genomic_DNA.
DR EMBL; U67358; AAC51219.1; JOINED; Genomic_DNA.
DR EMBL; U67360; AAC51219.1; JOINED; Genomic_DNA.
DR EMBL; U67361; AAC51219.1; JOINED; Genomic_DNA.
DR EMBL; U67362; AAC51219.1; JOINED; Genomic_DNA.
DR EMBL; U67363; AAC51219.1; JOINED; Genomic_DNA.
DR EMBL; U67364; AAC51219.1; JOINED; Genomic_DNA.
DR EMBL; U67365; AAC51219.1; JOINED; Genomic_DNA.
DR EMBL; U67366; AAC51219.1; JOINED; Genomic_DNA.
DR EMBL; U67367; AAC51219.1; JOINED; Genomic_DNA.
DR EMBL; U72263; AAB62718.1; -; mRNA.
DR EMBL; AK312375; BAG35293.1; -; mRNA.
DR EMBL; BX648142; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC068457; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC103854; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC134775; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68068.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68070.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68071.1; -; Genomic_DNA.
DR EMBL; BC010058; AAH10058.1; -; mRNA.
DR CCDS; CCDS53618.1; -. [Q93063-3]
DR CCDS; CCDS53619.1; -. [Q93063-2]
DR CCDS; CCDS7908.1; -. [Q93063-1]
DR RefSeq; NP_000392.3; NM_000401.3. [Q93063-3]
DR RefSeq; NP_001171554.1; NM_001178083.1. [Q93063-2]
DR RefSeq; NP_997005.1; NM_207122.1. [Q93063-1]
DR AlphaFoldDB; Q93063; -.
DR SMR; Q93063; -.
DR BioGRID; 108433; 111.
DR CORUM; Q93063; -.
DR IntAct; Q93063; 20.
DR MINT; Q93063; -.
DR STRING; 9606.ENSP00000379032; -.
DR CAZy; GT47; Glycosyltransferase Family 47.
DR CAZy; GT64; Glycosyltransferase Family 64.
DR GlyGen; Q93063; 2 sites.
DR iPTMnet; Q93063; -.
DR PhosphoSitePlus; Q93063; -.
DR BioMuta; EXT2; -.
DR DMDM; 3023739; -.
DR EPD; Q93063; -.
DR jPOST; Q93063; -.
DR MassIVE; Q93063; -.
DR MaxQB; Q93063; -.
DR PaxDb; Q93063; -.
DR PeptideAtlas; Q93063; -.
DR PRIDE; Q93063; -.
DR ProteomicsDB; 11685; -.
DR ProteomicsDB; 75696; -. [Q93063-1]
DR ProteomicsDB; 75697; -. [Q93063-2]
DR Antibodypedia; 26103; 241 antibodies from 29 providers.
DR DNASU; 2132; -.
DR Ensembl; ENST00000343631.4; ENSP00000342656.3; ENSG00000151348.16. [Q93063-1]
DR Ensembl; ENST00000358681.8; ENSP00000351509.4; ENSG00000151348.16. [Q93063-2]
DR Ensembl; ENST00000395673.8; ENSP00000379032.4; ENSG00000151348.16. [Q93063-1]
DR Ensembl; ENST00000533608.7; ENSP00000431173.2; ENSG00000151348.16. [Q93063-1]
DR Ensembl; ENST00000682993.1; ENSP00000507580.1; ENSG00000151348.16. [Q93063-1]
DR Ensembl; ENST00000683000.1; ENSP00000508361.1; ENSG00000151348.16. [Q93063-1]
DR GeneID; 2132; -.
DR KEGG; hsa:2132; -.
DR MANE-Select; ENST00000533608.7; ENSP00000431173.2; NM_207122.2; NP_997005.1.
DR UCSC; uc001mxz.4; human. [Q93063-1]
DR CTD; 2132; -.
DR DisGeNET; 2132; -.
DR GeneCards; EXT2; -.
DR GeneReviews; EXT2; -.
DR HGNC; HGNC:3513; EXT2.
DR HPA; ENSG00000151348; Low tissue specificity.
DR MalaCards; EXT2; -.
DR MIM; 133701; phenotype.
DR MIM; 601224; phenotype.
DR MIM; 608210; gene.
DR MIM; 616682; phenotype.
DR neXtProt; NX_Q93063; -.
DR OpenTargets; ENSG00000151348; -.
DR Orphanet; 321; Multiple osteochondromas.
DR Orphanet; 52022; Potocki-Shaffer syndrome.
DR Orphanet; 466926; Seizures-scoliosis-macrocephaly syndrome.
DR PharmGKB; PA27925; -.
DR VEuPathDB; HostDB:ENSG00000151348; -.
DR eggNOG; KOG1022; Eukaryota.
DR GeneTree; ENSGT00940000156620; -.
DR HOGENOM; CLU_013906_4_1_1; -.
DR InParanoid; Q93063; -.
DR OMA; NCTFWDC; -.
DR OrthoDB; 436779at2759; -.
DR PhylomeDB; Q93063; -.
DR TreeFam; TF314231; -.
DR BioCyc; MetaCyc:HS07726-MON; -.
DR BRENDA; 2.4.1.224; 2681.
DR BRENDA; 2.4.1.225; 2681.
DR PathwayCommons; Q93063; -.
DR Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR Reactome; R-HSA-3656237; Defective EXT2 causes exostoses 2.
DR Reactome; R-HSA-3656253; Defective EXT1 causes exostoses 1, TRPS2 and CHDS.
DR SignaLink; Q93063; -.
DR SIGNOR; Q93063; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 2132; 82 hits in 1081 CRISPR screens.
DR ChiTaRS; EXT2; human.
DR GeneWiki; EXT2_(gene); -.
DR GenomeRNAi; 2132; -.
DR Pharos; Q93063; Tbio.
DR PRO; PR:Q93063; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q93063; protein.
DR Bgee; ENSG00000151348; Expressed in stromal cell of endometrium and 185 other tissues.
DR Genevisible; Q93063; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:ProtInc.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0043541; C:UDP-N-acetylglucosamine transferase complex; IDA:BHF-UCL.
DR GO; GO:0050508; F:glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0015020; F:glucuronosyltransferase activity; IDA:BHF-UCL.
DR GO; GO:0016757; F:glycosyltransferase activity; IDA:BHF-UCL.
DR GO; GO:0042328; F:heparan sulfate N-acetylglucosaminyltransferase activity; NAS:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050509; F:N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL.
DR GO; GO:0033692; P:cellular polysaccharide biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEA:Ensembl.
DR GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0060350; P:endochondral bone morphogenesis; IEA:Ensembl.
DR GO; GO:0042044; P:fluid transport; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0060047; P:heart contraction; IEA:Ensembl.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0030210; P:heparin biosynthetic process; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; IEA:Ensembl.
DR GO; GO:0001503; P:ossification; IMP:BHF-UCL.
DR GO; GO:0006487; P:protein N-linked glycosylation; IEA:Ensembl.
DR GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0055078; P:sodium ion homeostasis; IEA:Ensembl.
DR GO; GO:0051923; P:sulfation; IEA:Ensembl.
DR GO; GO:0042311; P:vasodilation; IEA:Ensembl.
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 Alternative splicing; Disease variant; Disulfide bond;
KW Endoplasmic reticulum; Epilepsy; Glycoprotein; Glycosyltransferase;
KW Golgi apparatus; Hereditary multiple exostoses; Intellectual disability;
KW Manganese; Membrane; Metal-binding; Reference proteome; Signal-anchor;
KW Transferase; Transmembrane; Transmembrane helix; Tumor suppressor.
FT CHAIN 1..718
FT /note="Exostosin-2"
FT /id="PRO_0000149651"
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..718
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 628
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 490
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 517..522
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 538..540
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 540
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 569
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 624..628
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 662..673
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 637
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 626..676
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT VAR_SEQ 1
FT /note="M -> MSCASGSGGGLRHPLRCQKPWDEECEEEAVCVIM (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_046053"
FT VAR_SEQ 392..411
FT /note="ARWFWEAYFQSIKAIALATL -> LFMEPARRENWSAANHQMNSLIWPREQW
FT DS (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_001798"
FT VARIANT 42
FT /note="M -> V (in dbSNP:rs4755779)"
FT /id="VAR_033921"
FT VARIANT 85
FT /note="C -> R (in EXT2)"
FT /evidence="ECO:0000269|PubMed:10429361"
FT /id="VAR_012823"
FT VARIANT 87
FT /note="M -> R (in SSMS; decreased protein abundance; levels
FT of the EXT2-interacting protein NDST1 are abolished in
FT patient cells; dbSNP:rs140075817)"
FT /evidence="ECO:0000269|PubMed:26246518"
FT /id="VAR_076469"
FT VARIANT 95
FT /note="R -> C (in SSMS; decreased protein abundance; levels
FT of the EXT2-interacting protein NDST1 are abolished in
FT patient cells; dbSNP:rs376292686)"
FT /evidence="ECO:0000269|PubMed:26246518"
FT /id="VAR_076470"
FT VARIANT 152
FT /note="L -> R (in EXT2)"
FT /evidence="ECO:0000269|PubMed:10480354"
FT /id="VAR_012824"
FT VARIANT 179
FT /note="R -> S (in EXT2)"
FT /evidence="ECO:0000269|PubMed:11432960"
FT /id="VAR_012825"
FT VARIANT 202
FT /note="A -> V (in EXT2; dbSNP:rs771803942)"
FT /evidence="ECO:0000269|PubMed:11170095"
FT /id="VAR_012826"
FT VARIANT 223
FT /note="R -> P (in EXT2; dbSNP:rs764379119)"
FT /evidence="ECO:0000269|PubMed:10738008"
FT /id="VAR_012827"
FT VARIANT 227
FT /note="D -> N (in EXT2; no effect on oligomeric complex
FT formation with EXT1; dbSNP:rs121918280)"
FT /evidence="ECO:0000269|PubMed:11169766,
FT ECO:0000269|PubMed:11432960, ECO:0000269|PubMed:19344451,
FT ECO:0000269|PubMed:9326317"
FT /id="VAR_002378"
FT VARIANT 380
FT /note="I -> T (in EXT2)"
FT /evidence="ECO:0000269|PubMed:11668521"
FT /id="VAR_012828"
FT VARIANT 576
FT /note="E -> K (in osteochondroma; dbSNP:rs373582542)"
FT /evidence="ECO:0000269|PubMed:11668521"
FT /id="VAR_012829"
FT CONFLICT 322
FT /note="R -> H (in Ref. 5; BX648142)"
FT /evidence="ECO:0000305"
FT CONFLICT 568
FT /note="G -> D (in Ref. 4; AAB62718)"
FT /evidence="ECO:0000305"
FT CONFLICT Q93063-2:397
FT /note="A -> V (in Ref. 4; AAB62718)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 718 AA; 82255 MW; 9048CD3A5B63C5CB CRC64;
MCASVKYNIR GPALIPRMKT KHRIYYITLF SIVLLGLIAT GMFQFWPHSI ESSNDWNVEK
RSIRDVPVVR LPADSPIPER GDLSCRMHTC FDVYRCGFNP KNKIKVYIYA LKKYVDDFGV
SVSNTISREY NELLMAISDS DYYTDDINRA CLFVPSIDVL NQNTLRIKET AQAMAQLSRW
DRGTNHLLFN MLPGGPPDYN TALDVPRDRA LLAGGGFSTW TYRQGYDVSI PVYSPLSAEV
DLPEKGPGPR QYFLLSSQVG LHPEYREDLE ALQVKHGESV LVLDKCTNLS EGVLSVRKRC
HKHQVFDYPQ VLQEATFCVV LRGARLGQAV LSDVLQAGCV PVVIADSYIL PFSEVLDWKR
ASVVVPEEKM SDVYSILQSI PQRQIEEMQR QARWFWEAYF QSIKAIALAT LQIINDRIYP
YAAISYEEWN DPPAVKWGSV SNPLFLPLIP PQSQGFTAIV LTYDRVESLF RVITEVSKVP
SLSKLLVVWN NQNKNPPEDS LWPKIRVPLK VVRTAENKLS NRFFPYDEIE TEAVLAIDDD
IIMLTSDELQ FGYEVWREFP DRLVGYPGRL HLWDHEMNKW KYESEWTNEV SMVLTGAAFY
HKYFNYLYTY KMPGDIKNWV DAHMNCEDIA MNFLVANVTG KAVIKVTPRK KFKCPECTAI
DGLSLDQTHM VERSECINKF ASVFGTMPLK VVEHRADPVL YKDDFPEKLK SFPNIGSL
