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 02-SEP-2026, entry version 225. DE RecName: Full=Exostosin-2 {ECO:0000305}; DE EC=2.4.1.224 {ECO:0000269|PubMed:36593275}; DE AltName: Full=Exostosin glycosyltransferase 2 {ECO:0000312|HGNC:HGNC:3513}; DE AltName: Full=Glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase {ECO:0000303|PubMed:36593275}; DE AltName: Full=Heparan sulfate co-polymerase subunit EXT1 {ECO:0000303|PubMed:36593275}; DE AltName: Full=Multiple exostoses protein 2 {ECO:0000303|PubMed:8782816}; GN Name=EXT2 {ECO:0000312|HGNC:HGNC:3513}; 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), AND TISSUE SPECIFICITY. 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, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT EXT2 RP ASN-227. 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 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 [13] 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 [14] 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 [15] {ECO:0007744|PDB:7ZAY} RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) OF 47-718 OF THE HEPARAN RP SULFATE POLYMERASE, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DISULFIDE BONDS, RP GLYCOSYLATION AT ASN-637, AND MUTAGENESIS OF ARG-266; ASP-538 AND ASP-540. RX PubMed=36402845; DOI=10.1038/s41467-022-34882-6; RA Leisico F., Omeiri J., Le Narvor C., Beaudouin J., Hons M., Fenel D., RA Schoehn G., Coute Y., Bonnaffe D., Sadir R., Lortat-Jacob H., Wild R.; RT "Structure of the human heparan sulfate polymerase complex EXT1-EXT2."; RL Nat. Commun. 13:7110-7110(2022). RN [16] {ECO:0007744|PDB:7SCH, ECO:0007744|PDB:7SCJ, ECO:0007744|PDB:7SCK, ECO:0007744|PDB:7UQX, ECO:0007744|PDB:7UQY} RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) OF 46-718 OF THE HEPARAN RP SULFATE POLYMERASE IN COMPLEX WITH GLYCAN BACKBONE; UDP AND MANGANESE, RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PATHWAY, DISULFIDE BONDS, RP GLYCOSYLATION AT ASN-637, AND MUTAGENESIS OF TYR-308; ARG-325; GLN-328; RP ASP-538; ASP-540; ARG-569 AND GLU-585. RX PubMed=36593275; DOI=10.1038/s41589-022-01220-2; RA Li H., Chapla D., Amos R.A., Ramiah A., Moremen K.W., Li H.; RT "Structural basis for heparan sulfate co-polymerase action by the EXT1-2 RT complex."; RL Nat. Chem. Biol. 19:565-574(2023). RN [17] 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 [18] 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 [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] 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 [26] RP VARIANT EXT2 ASN-227, AND FUNCTION. 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 forming with EXT1 the heterodimeric CC heparan sulfate polymerase which catalyzes the elongation of the CC heparan sulfate glycan backbone (PubMed:22660413, PubMed:36402845, CC PubMed:36593275). Glycan backbone extension consists in the alternating CC transfer of (1->4)-beta-D-GlcA and (1->4)-alpha-D-GlcNAc residues from CC their respective UDP-sugar donors. Both EXT1 and EXT2 are required for CC the full activity of the polymerase since EXT1 bears the N- CC acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity CC within the complex while EXT2 carries the glucuronosyl-N- CC acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase CC activity (PubMed:36402845, PubMed:36593275). Heparan sulfate CC proteoglycans are ubiquitous components of the extracellular matrix and CC play an important role in tissue homeostasis and signaling CC (PubMed:19344451, PubMed:22660413). {ECO:0000269|PubMed:19344451, CC ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:36402845, CC ECO:0000269|PubMed:36593275}. 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] + UDP + H(+); 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; Evidence={ECO:0000269|PubMed:36402845, CC ECO:0000269|PubMed:36593275}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16214; CC Evidence={ECO:0000269|PubMed:36593275}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000269|PubMed:36593275}; CC -!- PATHWAY: Protein modification; protein glycosylation. CC {ECO:0000269|PubMed:36402845, ECO:0000269|PubMed:36593275}. CC -!- SUBUNIT: Part of the heparan sulfate polymerase, a dimeric complex CC composed of EXT1 and EXT2 (PubMed:10679296, PubMed:36402845, CC PubMed:36593275). Could also form homooligomeric complexes CC (PubMed:10679296). Interacts with NDST1 (PubMed:18337501, CC PubMed:35137078). Interacts with GALNT5 (PubMed:10545594). CC {ECO:0000269|PubMed:10545594, ECO:0000269|PubMed:10679296, CC ECO:0000269|PubMed:18337501, ECO:0000269|PubMed:35137078, CC ECO:0000269|PubMed:36402845, ECO:0000269|PubMed:36593275}. CC -!- INTERACTION: CC Q93063; Q16394: EXT1; NbExp=10; IntAct=EBI-1047761, EBI-1046007; CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000269|PubMed:10679296}; Single-pass type II membrane protein CC {ECO:0000255}. Golgi apparatus, cis-Golgi network membrane CC {ECO:0000269|PubMed:35137078}; Single-pass type II membrane protein CC {ECO:0000255}. Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:10679296}; Single-pass type II membrane protein CC {ECO:0000255}. Secreted {ECO:0000250|UniProtKB:O77783}. Note=The active CC heparan sulfate polymerase complex composed of EXT1 and EXT2 is CC localized to the Golgi apparatus. If both proteins are individually CC detected in the endoplasmic reticulum, the formation of the complex CC promotes their transport to the Golgi. {ECO:0000269|PubMed:10679296}. 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: Widely expressed. {ECO:0000269|PubMed:8782816}. CC -!- PTM: N-glycosylated at Asn-637. {ECO:0000269|PubMed:36402845, CC ECO:0000269|PubMed:36593275}. CC -!- PTM: A soluble form is generated by proteolytic processing. CC {ECO:0000250|UniProtKB:O77783}. 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:10679296, ECO:0000269|PubMed:10738008, CC ECO:0000269|PubMed:11169766, ECO:0000269|PubMed:11170095, CC ECO:0000269|PubMed:11432960, ECO:0000269|PubMed:11668521, CC ECO:0000269|PubMed:19344451, ECO:0000269|PubMed:9326317}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. 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="https://atlasgeneticsoncology.org/gene/213/EXT2"; 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; 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; 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_001178083.3. [Q93063-2] DR RefSeq; NP_001376557.1; NM_001389628.1. [Q93063-1] DR RefSeq; NP_001376559.1; NM_001389630.1. [Q93063-1] DR RefSeq; NP_997005.1; NM_207122.2. [Q93063-1] DR RefSeq; XP_047282486.1; XM_047426530.1. [Q93063-1] DR RefSeq; XP_054223951.1; XM_054367976.1. [Q93063-1] DR PDB; 7SCH; EM; 3.10 A; B=46-718. DR PDB; 7SCJ; EM; 3.40 A; B=46-718. DR PDB; 7SCK; EM; 2.80 A; B=46-718. DR PDB; 7UQX; EM; 3.30 A; B=46-718. DR PDB; 7UQY; EM; 3.00 A; B=46-718. DR PDB; 7ZAY; EM; 2.80 A; B=47-718. DR AlphaFoldDB; Q93063; -. DR EMDB; EMD-14582; -. DR EMDB; EMD-25035; -. DR EMDB; EMD-25036; -. DR EMDB; EMD-25037; -. DR EMDB; EMD-26701; -. DR EMDB; EMD-26702; -. DR SMR; Q93063; -. DR BioGRID; 108433; 132. DR ComplexPortal; CPX-8307; EXT1-EXT2 heparan sulfate biosynthesis complex. DR CORUM; Q93063; -. DR FunCoup; Q93063; 1828. DR IntAct; Q93063; 75. DR MINT; Q93063; -. DR NDEx; IQUERY-CP-EXT2; 4 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000379032; -. DR CAZy; GT47; Glycosyltransferase Family 47. DR CAZy; GT64; Glycosyltransferase Family 64. DR GlyCosmos; Q93063; 2 sites, No reported glycans. DR GlyGen; Q93063; 2 sites, 2 N-linked glycans (2 sites). DR iPTMnet; Q93063; -. DR PhosphoSitePlus; Q93063; -. DR SwissPalm; Q93063; -. DR BioMuta; EXT2; -. DR DMDM; 3023739; -. DR jPOST; Q93063; -. DR MassIVE; Q93063; -. DR PaxDb; 9606-ENSP00000379032; -. DR PeptideAtlas; Q93063; -. DR ProteomicsDB; 11685; -. DR ProteomicsDB; 75696; -. [Q93063-1] DR ProteomicsDB; 75697; -. [Q93063-2] DR Pumba; Q93063; -. DR Antibodypedia; 26103; 229 antibodies from 29 providers. DR DNASU; 2132; -. DR Ensembl; ENST00000343631.4; ENSP00000342656.3; ENSG00000151348.17. [Q93063-1] DR Ensembl; ENST00000358681.8; ENSP00000351509.4; ENSG00000151348.17. [Q93063-2] DR Ensembl; ENST00000395673.8; ENSP00000379032.4; ENSG00000151348.17. [Q93063-1] DR Ensembl; ENST00000533608.7; ENSP00000431173.2; ENSG00000151348.17. [Q93063-1] DR Ensembl; ENST00000682993.1; ENSP00000507580.1; ENSG00000151348.17. [Q93063-1] DR Ensembl; ENST00000683000.1; ENSP00000508361.1; ENSG00000151348.17. [Q93063-1] DR Ensembl; ENST00000860016.1; ENSP00000530075.1; ENSG00000151348.17. [Q93063-1] DR Ensembl; ENST00000860017.1; ENSP00000530076.1; ENSG00000151348.17. [Q93063-1] DR Ensembl; ENST00000860018.1; ENSP00000530077.1; ENSG00000151348.17. [Q93063-1] DR Ensembl; ENST00000860019.1; ENSP00000530078.1; ENSG00000151348.17. [Q93063-1] DR Ensembl; ENST00000860020.1; ENSP00000530079.1; ENSG00000151348.17. [Q93063-1] DR Ensembl; ENST00000860021.1; ENSP00000530080.1; ENSG00000151348.17. [Q93063-1] DR Ensembl; ENST00000958404.1; ENSP00000628463.1; ENSG00000151348.17. [Q93063-1] DR Ensembl; ENST00000958405.1; ENSP00000628464.1; ENSG00000151348.17. [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 AGR; HGNC:3513; -. DR ClinPGx; PA27925; -. 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 OpenTargets; ENSG00000151348; -. DR Orphanet; 321; Multiple osteochondromas. DR Orphanet; 52022; Potocki-Shaffer syndrome. DR Orphanet; 466926; Seizures-scoliosis-macrocephaly syndrome. 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; 5954868at2759; -. DR PAN-GO; Q93063; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q93063; -. DR BioCyc; MetaCyc:HS07726-MONOMER; -. 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 Agora; ENSG00000151348; -. DR BioGRID-ORCS; 2132; 86 hits in 1164 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 187 other cell types or tissues. DR ExpressionAtlas; Q93063; baseline and differential. DR GO; GO:1902494; C:catalytic complex; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; EXP:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; EXP:UniProtKB. 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; IDA:UniProtKB. 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:0050509; F:N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity; NAS:BHF-UCL. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL. DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; IDA:BHF-UCL. DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IDA:UniProtKB. DR GO; GO:0001503; P:ossification; IMP:BHF-UCL. DR GO; GO:0000271; P:polysaccharide biosynthetic process; IDA:BHF-UCL. DR FunFam; 3.90.550.10:FF:000035; Putative Exostosin-2; 1. DR Gene3D; 3.90.550.10; Spore Coat Polysaccharide Biosynthesis Protein SpsA, Chain A; 1. DR InterPro; IPR004263; Exostosin. DR InterPro; IPR040911; Exostosin_GT47. DR InterPro; IPR015338; GT64_dom. DR InterPro; IPR029044; Nucleotide-diphossugar_trans. DR PANTHER; PTHR48261; ACETYLGLUCOSAMINYLTRANSFERASE; 1. DR PANTHER; PTHR48261:SF5; EXOSTOSIN GLYCOSYLTRANSFERASE 2; 1. DR Pfam; PF03016; Exostosin_GT47; 1. DR Pfam; PF09258; Glyco_transf_64; 1. DR SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1. DR PDBsum; 7SCH; -. DR PDBsum; 7SCJ; -. DR PDBsum; 7SCK; -. DR PDBsum; 7UQX; -. DR PDBsum; 7UQY; -. DR PDBsum; 7ZAY; -. PE 1: Evidence at protein level; KW 3D-structure; 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; Proteomics identification; KW Reference proteome; Secreted; Signal-anchor; Transferase; Transmembrane; KW 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 BINDING 461 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000269|PubMed:36593275, FT ECO:0007744|PDB:7SCJ, ECO:0007744|PDB:7SCK, FT ECO:0007744|PDB:7UQX" FT BINDING 465 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000269|PubMed:36593275, FT ECO:0007744|PDB:7SCK" FT BINDING 465 FT /ligand="UDP-N-acetyl-alpha-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:57705" FT /evidence="ECO:0000250|UniProtKB:Q9ES89" FT BINDING 490 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000269|PubMed:36593275, FT ECO:0007744|PDB:7UQX" FT BINDING 490 FT /ligand="UDP-N-acetyl-alpha-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:57705" FT /evidence="ECO:0000250|UniProtKB:Q9ES89" FT BINDING 517 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000269|PubMed:36593275, FT ECO:0007744|PDB:7SCJ, ECO:0007744|PDB:7UQX" FT BINDING 517 FT /ligand="UDP-N-acetyl-alpha-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:57705" FT /evidence="ECO:0000250|UniProtKB:Q9ES89" FT BINDING 522 FT /ligand="UDP-N-acetyl-alpha-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:57705" FT /evidence="ECO:0000250|UniProtKB:Q9ES89" FT BINDING 538 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000269|PubMed:36593275, FT ECO:0007744|PDB:7UQX" FT BINDING 538 FT /ligand="UDP-N-acetyl-alpha-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:57705" FT /evidence="ECO:0000250|UniProtKB:Q9ES89" FT BINDING 539 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000269|PubMed:36593275, FT ECO:0007744|PDB:7SCK, ECO:0007744|PDB:7UQX" FT BINDING 539 FT /ligand="UDP-N-acetyl-alpha-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:57705" 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:0000269|PubMed:36593275, FT ECO:0007744|PDB:7SCK" FT BINDING 540 FT /ligand="UDP-N-acetyl-alpha-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:57705" FT /evidence="ECO:0000250|UniProtKB:Q9ES89" FT BINDING 582 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /ligand_part="O(3)-(poly[(1->4)-beta-D-glucuronosyl-(1->4)- FT N-acetyl-alpha-D-glucosaminyl]-(1->4)-beta-D-glucuronosyl- FT (1->3)-beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)- FT beta-D-xylosyl)-L-serine residue" FT /ligand_part_id="ChEBI:CHEBI:132415" FT /evidence="ECO:0000305|PubMed:36593275, FT ECO:0007744|PDB:7SCK" FT BINDING 584 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /ligand_part="O(3)-(poly[(1->4)-beta-D-glucuronosyl-(1->4)- FT N-acetyl-alpha-D-glucosaminyl]-(1->4)-beta-D-glucuronosyl- FT (1->3)-beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)- FT beta-D-xylosyl)-L-serine residue" FT /ligand_part_id="ChEBI:CHEBI:132415" FT /evidence="ECO:0000305|PubMed:36593275, FT ECO:0007744|PDB:7SCK" FT BINDING 627 FT /ligand="UDP-N-acetyl-alpha-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:57705" FT /evidence="ECO:0000250|UniProtKB:Q9ES89" FT BINDING 628 FT /ligand="UDP-N-acetyl-alpha-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:57705" FT /evidence="ECO:0000250|UniProtKB:Q9ES89" FT BINDING 651 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /ligand_part="O(3)-(poly[(1->4)-beta-D-glucuronosyl-(1->4)- FT N-acetyl-alpha-D-glucosaminyl]-(1->4)-beta-D-glucuronosyl- FT (1->3)-beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)- FT beta-D-xylosyl)-L-serine residue" FT /ligand_part_id="ChEBI:CHEBI:132415" FT /evidence="ECO:0000305|PubMed:36593275, FT ECO:0007744|PDB:7SCK" FT BINDING 653 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /ligand_part="O(3)-(poly[(1->4)-beta-D-glucuronosyl-(1->4)- FT N-acetyl-alpha-D-glucosaminyl]-(1->4)-beta-D-glucuronosyl- FT (1->3)-beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)- FT beta-D-xylosyl)-L-serine residue" FT /ligand_part_id="ChEBI:CHEBI:132415" FT /evidence="ECO:0000305|PubMed:36593275, FT ECO:0007744|PDB:7SCK" FT BINDING 673 FT /ligand="UDP-N-acetyl-alpha-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:57705" 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:0000269|PubMed:36402845, FT ECO:0000269|PubMed:36593275, ECO:0007744|PDB:7SCH, FT ECO:0007744|PDB:7SCJ, ECO:0007744|PDB:7SCK, FT ECO:0007744|PDB:7UQX, ECO:0007744|PDB:7UQY, FT ECO:0007744|PDB:7ZAY" FT DISULFID 85..90 FT /evidence="ECO:0000269|PubMed:36402845, FT ECO:0000269|PubMed:36593275, ECO:0007744|PDB:7SCH, FT ECO:0007744|PDB:7SCJ, ECO:0007744|PDB:7SCK, FT ECO:0007744|PDB:7UQX, ECO:0007744|PDB:7UQY, FT ECO:0007744|PDB:7ZAY" FT DISULFID 96..151 FT /evidence="ECO:0000269|PubMed:36402845, FT ECO:0000269|PubMed:36593275, ECO:0007744|PDB:7SCH, FT ECO:0007744|PDB:7SCJ, ECO:0007744|PDB:7SCK, FT ECO:0007744|PDB:7UQX, ECO:0007744|PDB:7UQY, FT ECO:0007744|PDB:7ZAY" FT DISULFID 286..300 FT /evidence="ECO:0000269|PubMed:36402845, FT ECO:0007744|PDB:7ZAY" FT DISULFID 318..339 FT /evidence="ECO:0000269|PubMed:36402845, FT ECO:0000269|PubMed:36593275, ECO:0007744|PDB:7SCH, FT ECO:0007744|PDB:7SCJ, ECO:0007744|PDB:7SCK, FT ECO:0007744|PDB:7UQX, ECO:0007744|PDB:7UQY, FT ECO:0007744|PDB:7ZAY" FT DISULFID 626..676 FT /evidence="ECO:0000269|PubMed:36402845, FT ECO:0000269|PubMed:36593275, ECO:0007744|PDB:7SCH, FT ECO:0007744|PDB:7SCJ, ECO:0007744|PDB:7SCK, FT ECO:0007744|PDB:7UQX, ECO:0007744|PDB:7UQY, FT ECO:0007744|PDB:7ZAY" 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:10679296, FT ECO:0000269|PubMed:11169766, ECO:0000269|PubMed:11432960, FT ECO:0000269|PubMed:19344451, 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 MUTAGEN 266 FT /note="R->A: No effect on N-acetylglucosaminyl-proteoglycan FT 4-beta-glucuronosyltransferase activity." FT /evidence="ECO:0000269|PubMed:36402845" FT MUTAGEN 308 FT /note="Y->A: Increased N-acetylglucosaminyl-proteoglycan FT 4-beta-glucuronosyltransferase activity. Decreased FT glucuronosyl-N-acetylglucosaminyl-proteoglycan FT 4-alpha-N-acetylglucosaminyltransferase activity." FT /evidence="ECO:0000269|PubMed:36593275" FT MUTAGEN 325 FT /note="R->A: Increased N-acetylglucosaminyl-proteoglycan FT 4-beta-glucuronosyltransferase activity. No effect on FT glucuronosyl-N-acetylglucosaminyl-proteoglycan FT 4-alpha-N-acetylglucosaminyltransferase activity." FT /evidence="ECO:0000269|PubMed:36593275" FT MUTAGEN 328 FT /note="Q->A: No effect on N-acetylglucosaminyl-proteoglycan FT 4-beta-glucuronosyltransferase activity. No effect on FT glucuronosyl-N-acetylglucosaminyl-proteoglycan FT 4-alpha-N-acetylglucosaminyltransferase activity." FT /evidence="ECO:0000269|PubMed:36593275" FT MUTAGEN 538 FT /note="D->A: Decreased N-acetylglucosaminyl-proteoglycan FT 4-beta-glucuronosyltransferase activity. Loss of FT glucuronosyl-N-acetylglucosaminyl-proteoglycan FT 4-alpha-N-acetylglucosaminyltransferase activity." FT /evidence="ECO:0000269|PubMed:36593275" FT MUTAGEN 538 FT /note="D->N: Decreased FT glucuronosyl-N-acetylglucosaminyl-proteoglycan FT 4-alpha-N-acetylglucosaminyltransferase activity; when FT associated with N-540." FT /evidence="ECO:0000269|PubMed:36402845" FT MUTAGEN 540 FT /note="D->A: Increased N-acetylglucosaminyl-proteoglycan FT 4-beta-glucuronosyltransferase activity. Decreased FT glucuronosyl-N-acetylglucosaminyl-proteoglycan FT 4-alpha-N-acetylglucosaminyltransferase activity." FT /evidence="ECO:0000269|PubMed:36593275" FT MUTAGEN 540 FT /note="D->N: Decreased FT glucuronosyl-N-acetylglucosaminyl-proteoglycan FT 4-alpha-N-acetylglucosaminyltransferase activity; when FT associated with N-538." FT /evidence="ECO:0000269|PubMed:36402845" FT MUTAGEN 569 FT /note="R->A: Increased N-acetylglucosaminyl-proteoglycan FT 4-beta-glucuronosyltransferase activity. Loss of FT glucuronosyl-N-acetylglucosaminyl-proteoglycan FT 4-alpha-N-acetylglucosaminyltransferase activity." FT /evidence="ECO:0000269|PubMed:36593275" FT MUTAGEN 585 FT /note="E->A: Decreased N-acetylglucosaminyl-proteoglycan FT 4-beta-glucuronosyltransferase activity. Decreased FT glucuronosyl-N-acetylglucosaminyl-proteoglycan FT 4-alpha-N-acetylglucosaminyltransferase activity." FT /evidence="ECO:0000269|PubMed:36593275" 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 HELIX 78..81 FT /evidence="ECO:0007829|PDB:7UQY" FT HELIX 87..90 FT /evidence="ECO:0007829|PDB:7SCK" FT TURN 93..96 FT /evidence="ECO:0007829|PDB:7UQY" FT STRAND 106..108 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 109..111 FT /evidence="ECO:0007829|PDB:7ZAY" FT HELIX 124..127 FT /evidence="ECO:0007829|PDB:7ZAY" FT HELIX 128..138 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 140..143 FT /evidence="ECO:0007829|PDB:7SCJ" FT TURN 147..149 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 151..154 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 162..164 FT /evidence="ECO:0007829|PDB:7ZAY" FT HELIX 167..176 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 181..183 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 184..189 FT /evidence="ECO:0007829|PDB:7SCK" FT TURN 196..198 FT /evidence="ECO:0007829|PDB:7ZAY" FT STRAND 211..215 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 219..221 FT /evidence="ECO:0007829|PDB:7SCK" FT TURN 224..226 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 227..229 FT /evidence="ECO:0007829|PDB:7ZAY" FT HELIX 232..234 FT /evidence="ECO:0007829|PDB:7ZAY" FT HELIX 236..239 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 251..257 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 263..276 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 278..284 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 298..303 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 305..307 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 308..311 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 312..314 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 315..320 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 323..326 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 330..337 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 340..343 FT /evidence="ECO:0007829|PDB:7SCK" FT TURN 351..355 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 358..360 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 368..370 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 373..378 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 382..395 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 396..400 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 403..418 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 420..422 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 423..425 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 427..430 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 433..438 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 452..454 FT /evidence="ECO:0007829|PDB:7ZAY" FT STRAND 456..464 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 466..476 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 479..481 FT /evidence="ECO:0007829|PDB:7UQY" FT STRAND 482..489 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 492..494 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 495..498 FT /evidence="ECO:0007829|PDB:7SCK" FT TURN 499..501 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 509..513 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 519..523 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 531..538 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 546..558 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 562..567 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 570..574 FT /evidence="ECO:0007829|PDB:7SCK" FT TURN 575..578 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 579..583 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 588..590 FT /evidence="ECO:0007829|PDB:7UQY" FT STRAND 597..601 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 602..611 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 616..623 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 627..639 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 644..648 FT /evidence="ECO:0007829|PDB:7SCK" FT HELIX 669..684 FT /evidence="ECO:0007829|PDB:7SCK" FT STRAND 695..698 FT /evidence="ECO:0007829|PDB:7SCK" FT TURN 699..702 FT /evidence="ECO:0007829|PDB:7SCK" FT TURN 707..709 FT /evidence="ECO:0007829|PDB:7SCK" 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 //