ID EXT1_HUMAN Reviewed; 746 AA. AC Q16394; B2R7V2; Q9BVI9; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 27-MAR-2002, sequence version 2. DT 16-MAR-2016, entry version 165. DE RecName: Full=Exostosin-1; 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 1; DE AltName: Full=Putative tumor suppressor protein EXT1; GN Name=EXT1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Placenta; RX PubMed=7550340; DOI=10.1038/ng1095-137; RA Ahn J., Luedecke H.-J., Lindow S., Horton W.A., Lee B., Wagner M.J., RA Horsthemke B., Wells D.E.; RT "Cloning of the putative tumour suppressor gene for hereditary RT multiple exostoses (EXT1)."; RL Nat. Genet. 11:137-143(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Tongue; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-320. RC TISSUE=Lung; RX PubMed=9119404; DOI=10.1006/geno.1996.4577; RA Luedecke H.-J., Ahn J., Lin X., Hill A., Wagner M.J., Schomburg L., RA Horsthemke B., Wells D.E.; RT "Genomic organization and promoter structure of the human EXT1 gene."; RL Genomics 40:351-354(1997). RN [6] 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 RT products, in Golgi apparatus."; RL Biochem. Biophys. Res. Commun. 268:860-867(2000). RN [7] RP FUNCTION. RX PubMed=11518722; DOI=10.1172/JCI13737; RA Duncan G., McCormick C., Tufaro F.; RT "The link between heparan sulfate and hereditary bone disease: finding RT a function for the EXT family of putative tumor suppressor proteins."; RL J. Clin. Invest. 108:511-516(2001). RN [8] RP FUNCTION. RX PubMed=22660413; DOI=10.1038/ncb2502; RA Baietti M.F., Zhang Z., Mortier E., Melchior A., Degeest G., RA Geeraerts A., Ivarsson Y., Depoortere F., Coomans C., Vermeiren E., RA Zimmermann P., David G.; RT "Syndecan-syntenin-ALIX regulates the biogenesis of exosomes."; RL Nat. Cell Biol. 14:677-685(2012). RN [9] 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 [10] RP VARIANTS EXT1 GLY-280 AND HIS-340. RA Raskind W.H., Matsushita M., Conrad E.U. III, Wells D.E., RA Sandell L.J., Wagner M.J., Houck J.; RT "Spectrum of EXT1 mutations in hereditary multiple exostoses."; RL Am. J. Hum. Genet. 59:A280-A280(1996). RN [11] RP VARIANT EXT1 LEU-340. RX PubMed=8981950; RA Hecht J.T., Hogue D.A., Wang Y., Blanton S.H., Wagner M.J., RA Strong L.C., Raskind W.H., Hansen M.F., Wells D.E.; RT "Hereditary multiple exostoses (EXT): mutational studies of familial RT EXT1 cases and EXT-associated malignancies."; RL Am. J. Hum. Genet. 60:80-86(1997). RN [12] RP VARIANTS EXT1 ASP-339 AND CYS-340. 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 RT hereditary multiple exostoses."; RL Am. J. Hum. Genet. 61:520-528(1997). RN [13] RP VARIANTS EXT1 GLY-280 AND SER-340. RX PubMed=9463333; DOI=10.1086/301726; RA Wuyts W., van Hul W., de Boulle K., Hendrickx J., Bakker E., RA Vanhoenacker F., Mollica F., Luedecke H.-J., Sayli B.S., RA Pazzaglia U.E., Mortier G., Hamel B.C.J., Conrad E.U. III, RA Matsushita M., Raskind W.H., Willems P.J.; RT "Mutations in the EXT1 and EXT2 genes in hereditary multiple RT exostoses."; RL Am. J. Hum. Genet. 62:346-354(1998). RN [14] RP VARIANTS EXT1 GLY-280; SER-280; HIS-340 AND HIS-627 DEL. RX PubMed=9521425; RX DOI=10.1002/(SICI)1098-1004(1998)11:3<231::AID-HUMU8>3.0.CO;2-K; RA Raskind W.H., Conrad E.U. III, Matsushita M., Wijsman E.M., RA Wells D.E., Chapman N., Sandell L.J., Wagner M.J., Houck J.; RT "Evaluation of locus heterogeneity and EXT1 mutations in 34 families RT with hereditary multiple exostoses."; RL Hum. Mutat. 11:231-239(1998). RN [15] RP VARIANTS EXT1 HIS-164; 235-PRO--LYS-239 DEL AND SER-316. RX PubMed=10441575; DOI=10.1086/302532; RA Bovee J.V.M.G., Cleton-Jansen A.-M., Wuyts W., Caethoven G., RA Taminiau A.H.M., Bakker E., van Hul W., Cornelisse C.J., RA Hogendoorn P.C.W.; RT "EXT-mutation analysis and loss of heterozygosity in sporadic and RT hereditary osteochondromas and secondary chondrosarcomas."; RL Am. J. Hum. Genet. 65:689-698(1999). RN [16] RP VARIANTS EXT1 VAL-486 AND LEU-496. RX PubMed=10480354; DOI=10.1007/s004399900058; RA Xu L., Xia J., Jiang H., Zhou J., Li H., Wang D., Pan Q., Long Z., RA Fan C., Deng H.-X.; RT "Mutation analysis of hereditary multiple exostoses in the Chinese."; RL Hum. Genet. 105:45-50(1999). RN [17] RP VARIANT EXT1 215-MET--SER-221 DEL, AND VARIANT OSTEOCHONDROMA RP 215-MET--SER-222 DELINS ILE. 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 RT EXT2 in exostosis chondrocytes."; RL Cell Motil. Cytoskeleton 48:149-162(2001). RN [18] RP CHARACTERIZATION OF VARIANTS, AND MUTAGENESIS OF GLN-27; ASP-164; RP ASN-316; ALA-486 AND PRO-496. RX PubMed=11391482; DOI=10.1086/321278; RA Cheung P.K., McCormick C., Crawford B.E., Esko J.D., Tufaro F., RA Duncan G.; RT "Etiological point mutations in the hereditary multiple exostoses gene RT EXT1: a functional analysis of heparan sulfate polymerase activity."; RL Am. J. Hum. Genet. 69:55-66(2001). CC -!- FUNCTION: Glycosyltransferase required for the biosynthesis of CC heparan-sulfate. The EXT1/EXT2 complex possesses substantially CC higher glycosyltransferase activity than EXT1 or EXT2 alone. CC Appears to be a tumor suppressor. Required for the exosomal CC release of SDCBP, CD63 and syndecan (PubMed:22660413). CC {ECO:0000269|PubMed:11518722, ECO:0000269|PubMed:22660413}. CC -!- CATALYTIC ACTIVITY: UDP-N-acetyl-D-glucosamine + beta-D- CC glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan = CC UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl- CC (1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan. CC -!- CATALYTIC ACTIVITY: UDP-alpha-D-glucuronate + N-acetyl-alpha-D- CC glucosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan = UDP + beta- CC D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D- CC glucuronosyl-proteoglycan. 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/hetero-oligomeric complex with EXT2. CC {ECO:0000269|PubMed:10679296}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:10679296}; Single-pass type II membrane CC protein {ECO:0000269|PubMed:10679296}. Golgi apparatus membrane CC {ECO:0000269|PubMed:10679296}; Single-pass type II membrane CC protein {ECO:0000269|PubMed:10679296}. Note=The EXT1/EXT2 complex CC is localized in the Golgi apparatus. CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- DISEASE: Hereditary multiple exostoses 1 (EXT1) [MIM:133700]: EXT CC is a genetically heterogeneous bone disorder caused by genes CC segregating on human chromosomes 8, 11, and 19 and designated CC EXT1, EXT2 and EXT3 respectively. EXT is a dominantly inherited CC skeletal disorder primarily affecting endochondral bone during CC growth. The disease is characterized by formation of numerous CC cartilage-capped, benign bone tumors (osteocartilaginous exostoses CC or osteochondromas) that are often accompanied by skeletal CC deformities and short stature. In a small percentage of cases CC exostoses have exhibited malignant transformation resulting in an CC osteosarcoma or chondrosarcoma. Osteochondromas development can CC also occur as a sporadic event. {ECO:0000269|PubMed:10441575, CC ECO:0000269|PubMed:10480354, ECO:0000269|PubMed:11169766, CC ECO:0000269|PubMed:8981950, ECO:0000269|PubMed:9326317, CC ECO:0000269|PubMed:9463333, ECO:0000269|PubMed:9521425, CC ECO:0000269|Ref.10}. Note=The disease is caused by mutations CC affecting the gene represented in this entry. CC -!- DISEASE: Tricho-rhino-phalangeal syndrome 2 (TRPS2) [MIM:150230]: CC A syndrome that combines the clinical features of tricho-rhino- CC phalangeal syndrome type 1 and multiple exostoses type 1. Affected CC individuals manifest multiple dysmorphic facial features including CC large, laterally protruding ears, a bulbous nose, an elongated CC upper lip, as well as sparse scalp hair, winged scapulae, multiple CC cartilaginous exostoses, redundant skin, and mental retardation. CC Note=The gene represented in this entry is involved in disease CC pathogenesis. A chromosomal aberration resulting in the loss of CC functional copies of TRPS1 and EXT1 has been found in TRPS2 CC patients. CC -!- DISEASE: Chondrosarcoma (CHDSA) [MIM:215300]: A malignant neoplasm CC derived from cartilage cells. Chondrosarcomas range from slow- CC growing non-metastasizing lesions to highly aggressive CC metastasizing sarcomas. Note=The disease is caused by mutations CC affecting the gene represented 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 CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/EXT1ID212.html"; CC -!- WEB RESOURCE: Name=GGDB; Note=GlycoGene database; CC URL="http://jcggdb.jp/rcmg/ggdb/Homolog?cat=symbol&symbol=EXT1"; 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; S79639; AAB62283.1; -; mRNA. DR EMBL; AK313129; BAG35949.1; -; mRNA. DR EMBL; CH471060; EAW91972.1; -; Genomic_DNA. DR EMBL; BC001174; AAH01174.1; -; mRNA. DR EMBL; U70539; AAC51154.1; -; Genomic_DNA. DR CCDS; CCDS6324.1; -. DR RefSeq; NP_000118.2; NM_000127.2. DR UniGene; Hs.492618; -. DR ProteinModelPortal; Q16394; -. DR SMR; Q16394; 512-724. DR BioGrid; 108432; 22. DR IntAct; Q16394; 2. DR MINT; MINT-120274; -. DR STRING; 9606.ENSP00000367446; -. DR CAZy; GT47; Glycosyltransferase Family 47. DR CAZy; GT64; Glycosyltransferase Family 64. DR iPTMnet; Q16394; -. DR PhosphoSite; Q16394; -. DR BioMuta; EXT1; -. DR DMDM; 20141422; -. DR EPD; Q16394; -. DR MaxQB; Q16394; -. DR PaxDb; Q16394; -. DR PRIDE; Q16394; -. DR DNASU; 2131; -. DR Ensembl; ENST00000378204; ENSP00000367446; ENSG00000182197. DR GeneID; 2131; -. DR KEGG; hsa:2131; -. DR UCSC; uc003yok.3; human. DR CTD; 2131; -. DR GeneCards; EXT1; -. DR GeneReviews; EXT1; -. DR HGNC; HGNC:3512; EXT1. DR HPA; HPA044394; -. DR MalaCards; EXT1; -. DR MIM; 133700; phenotype. DR MIM; 150230; phenotype. DR MIM; 215300; phenotype. DR MIM; 608177; gene. DR neXtProt; NX_Q16394; -. DR Orphanet; 55880; Chondrosarcoma. DR Orphanet; 502; Langer-Giedion syndrome. DR Orphanet; 321; Multiple osteochondromas. DR PharmGKB; PA27924; -. DR eggNOG; KOG1021; Eukaryota. DR eggNOG; ENOG410XTFH; LUCA. DR GeneTree; ENSGT00550000074496; -. DR HOGENOM; HOG000266990; -. DR HOVERGEN; HBG003459; -. DR InParanoid; Q16394; -. DR KO; K02366; -. DR OMA; CFDFTKC; -. DR OrthoDB; EOG7RBZ7Z; -. DR PhylomeDB; Q16394; -. DR TreeFam; TF314231; -. DR BioCyc; MetaCyc:HS00012-MONOMER; -. DR BRENDA; 2.4.1.224; 2681. DR BRENDA; 2.4.1.225; 2681. DR Reactome; R-HSA-2022928; HS-GAG biosynthesis. DR Reactome; R-HSA-3656253; Defective EXT1 causes exostoses 1, TRPS2 and CHDS. DR UniPathway; UPA00378; -. DR ChiTaRS; EXT1; human. DR GeneWiki; EXT1; -. DR GenomeRNAi; 2131; -. DR NextBio; 8611; -. DR PRO; PR:Q16394; -. DR Proteomes; UP000005640; Chromosome 8. DR Bgee; Q16394; -. DR CleanEx; HS_EXT1; -. DR ExpressionAtlas; Q16394; baseline and differential. DR Genevisible; Q16394; HS. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0005789; C:endoplasmic reticulum membrane; NAS:BHF-UCL. DR GO; GO:0005794; C:Golgi apparatus; IDA:BHF-UCL. DR GO; GO:0000139; C:Golgi membrane; TAS:BHF-UCL. DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc. DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; IDA:BHF-UCL. DR GO; GO:0050508; F:glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity; ISS:UniProtKB. DR GO; GO:0015020; F:glucuronosyltransferase 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; ISS:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL. DR GO; GO:0016757; F:transferase activity, transferring glycosyl groups; IDA:BHF-UCL. DR GO; GO:0007411; P:axon guidance; IEA:Ensembl. DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:Reactome. DR GO; GO:0033692; P:cellular polysaccharide biosynthetic process; IDA:BHF-UCL. DR GO; GO:0072498; P:embryonic skeletal joint development; IEA:Ensembl. DR GO; GO:0007492; P:endoderm development; IEA:Ensembl. DR GO; GO:0007369; P:gastrulation; IEA:Ensembl. DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; IDA:BHF-UCL. DR GO; GO:0030203; P:glycosaminoglycan metabolic process; TAS:Reactome. DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; ISS:UniProtKB. DR GO; GO:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; IMP:BHF-UCL. DR GO; GO:0007498; P:mesoderm development; IEA:Ensembl. DR GO; GO:0021772; P:olfactory bulb development; IEA:Ensembl. DR GO; GO:0001503; P:ossification; IMP:BHF-UCL. DR GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR Gene3D; 3.90.550.10; -; 1. DR InterPro; IPR004263; Exostosin. DR InterPro; IPR027670; Exostosin-1. DR InterPro; IPR015338; EXT_C. DR InterPro; IPR029044; Nucleotide-diphossugar_trans. DR PANTHER; PTHR11062:SF97; PTHR11062:SF97; 2. DR Pfam; PF03016; Exostosin; 1. DR Pfam; PF09258; Glyco_transf_64; 1. DR SUPFAM; SSF53448; SSF53448; 1. PE 1: Evidence at protein level; KW Complete proteome; Disease mutation; Disulfide bond; KW Endoplasmic reticulum; Glycoprotein; Glycosyltransferase; KW Golgi apparatus; Hereditary multiple exostoses; Manganese; Membrane; KW Metal-binding; Reference proteome; Signal-anchor; Transferase; KW Transmembrane; Transmembrane helix; Tumor suppressor. FT CHAIN 1 746 Exostosin-1. FT /FTId=PRO_0000149648. FT TOPO_DOM 1 7 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 8 28 Helical; Signal-anchor for type II FT membrane protein. {ECO:0000255}. FT TOPO_DOM 29 746 Lumenal. {ECO:0000255}. FT REGION 544 549 Substrate binding. FT {ECO:0000250|UniProtKB:Q9ES89}. FT REGION 565 567 Substrate binding. FT {ECO:0000250|UniProtKB:Q9ES89}. FT REGION 650 654 Substrate binding. FT {ECO:0000250|UniProtKB:Q9ES89}. FT REGION 688 701 Substrate binding. FT {ECO:0000250|UniProtKB:Q9ES89}. FT ACT_SITE 654 654 {ECO:0000250|UniProtKB:Q9ES89}. FT METAL 567 567 Manganese; catalytic. FT {ECO:0000250|UniProtKB:Q9ES89}. FT BINDING 518 518 Substrate. FT {ECO:0000250|UniProtKB:Q9ES89}. FT BINDING 595 595 Substrate. FT {ECO:0000250|UniProtKB:Q9ES89}. FT CARBOHYD 89 89 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 330 330 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 652 704 {ECO:0000250|UniProtKB:Q9ES89}. FT VARIANT 27 27 Q -> K (in EXT1; no loss of activity). FT /FTId=VAR_012815. FT VARIANT 164 164 D -> H (in EXT1; loss of activity). FT {ECO:0000269|PubMed:10441575}. FT /FTId=VAR_012816. FT VARIANT 215 222 MLAKASIS -> I (in isolated FT osteochondroma; somatic mutation). FT {ECO:0000269|PubMed:11169766}. FT /FTId=VAR_012818. FT VARIANT 215 221 Missing (in EXT1). FT /FTId=VAR_012817. FT VARIANT 235 239 Missing (in multiple osteochondromas). FT {ECO:0000269|PubMed:10441575}. FT /FTId=VAR_012819. FT VARIANT 280 280 R -> G (in EXT1; loss of activity). FT {ECO:0000269|PubMed:9463333, FT ECO:0000269|PubMed:9521425, FT ECO:0000269|Ref.10}. FT /FTId=VAR_002370. FT VARIANT 280 280 R -> S (in EXT1; loss of activity). FT {ECO:0000269|PubMed:9521425}. FT /FTId=VAR_002371. FT VARIANT 316 316 N -> S (in chondrosarcoma; no loss of FT activity). {ECO:0000269|PubMed:10441575}. FT /FTId=VAR_012820. FT VARIANT 339 339 G -> D (in EXT1; loss of activity). FT {ECO:0000269|PubMed:9326317}. FT /FTId=VAR_002372. FT VARIANT 340 340 R -> C (in EXT1; loss of activity; still FT able to form an oligomeric complex). FT {ECO:0000269|PubMed:9326317}. FT /FTId=VAR_002373. FT VARIANT 340 340 R -> H (in EXT1; loss of activity). FT {ECO:0000269|PubMed:9521425, FT ECO:0000269|Ref.10}. FT /FTId=VAR_002374. FT VARIANT 340 340 R -> L (in EXT1; loss of activity). FT {ECO:0000269|PubMed:8981950}. FT /FTId=VAR_002375. FT VARIANT 340 340 R -> S (in EXT1; loss of activity). FT {ECO:0000269|PubMed:9463333}. FT /FTId=VAR_002376. FT VARIANT 486 486 A -> V (in EXT1; no loss of activity; FT dbSNP:rs188859975). FT {ECO:0000269|PubMed:10480354}. FT /FTId=VAR_012821. FT VARIANT 496 496 P -> L (in EXT1; no loss of activity). FT {ECO:0000269|PubMed:10480354}. FT /FTId=VAR_012822. FT VARIANT 627 627 Missing (in EXT1; loss of activity). FT {ECO:0000269|PubMed:9521425}. FT /FTId=VAR_002377. FT MUTAGEN 27 27 Q->A,P: No effect on heparan-sulfate FT biosynthesis. FT {ECO:0000269|PubMed:11391482}. FT MUTAGEN 27 27 Missing: No effect on heparan-sulfate FT biosynthesis. FT {ECO:0000269|PubMed:11391482}. FT MUTAGEN 164 164 D->E: Abolishes heparan-sulfate FT biosynthesis. FT {ECO:0000269|PubMed:11391482}. FT MUTAGEN 164 164 Missing: Abolishes heparan-sulfate FT biosynthesis. FT {ECO:0000269|PubMed:11391482}. FT MUTAGEN 316 316 N->A: No effect on heparan-sulfate FT biosynthesis. FT {ECO:0000269|PubMed:11391482}. FT MUTAGEN 316 316 Missing: No effect on heparan-sulfate FT biosynthesis. FT {ECO:0000269|PubMed:11391482}. FT MUTAGEN 486 486 A->H: No effect on heparan-sulfate FT biosynthesis. FT {ECO:0000269|PubMed:11391482}. FT MUTAGEN 486 486 Missing: No effect on heparan-sulfate FT biosynthesis. FT {ECO:0000269|PubMed:11391482}. FT MUTAGEN 496 496 P->H: No effect on heparan-sulfate FT biosynthesis. FT {ECO:0000269|PubMed:11391482}. FT MUTAGEN 496 496 Missing: No effect on heparan-sulfate FT biosynthesis. FT {ECO:0000269|PubMed:11391482}. FT CONFLICT 60 61 DA -> EP (in Ref. 1 and 3). FT {ECO:0000305}. SQ SEQUENCE 746 AA; 86255 MW; 842CD7E6C1312C1A CRC64; MQAKKRYFIL LSAGSCLALL FYFGGLQFRA SRSHSRREEH SGRNGLHHPS PDHFWPRFPD ALRPFVPWDQ LENEDSSVHI SPRQKRDANS SIYKGKKCRM ESCFDFTLCK KNGFKVYVYP QQKGEKIAES YQNILAAIEG SRFYTSDPSQ ACLFVLSLDT LDRDQLSPQY VHNLRSKVQS LHLWNNGRNH LIFNLYSGTW PDYTEDVGFD IGQAMLAKAS ISTENFRPNF DVSIPLFSKD HPRTGGERGF LKFNTIPPLR KYMLVFKGKR YLTGIGSDTR NALYHVHNGE DVVLLTTCKH GKDWQKHKDS RCDRDNTEYE KYDYREMLHN ATFCLVPRGR RLGSFRFLEA LQAACVPVML SNGWELPFSE VINWNQAAVI GDERLLLQIP STIRSIHQDK ILALRQQTQF LWEAYFSSVE KIVLTTLEII QDRIFKHISR NSLIWNKHPG GLFVLPQYSS YLGDFPYYYA NLGLKPPSKF TAVIHAVTPL VSQSQPVLKL LVAAAKSQYC AQIIVLWNCD KPLPAKHRWP ATAVPVVVIE GESKVMSSRF LPYDNIITDA VLSLDEDTVL STTEVDFAFT VWQSFPERIV GYPARSHFWD NSKERWGYTS KWTNDYSMVL TGAAIYHKYY HYLYSHYLPA SLKNMVDQLA NCEDILMNFL VSAVTKLPPI KVTQKKQYKE TMMGQTSRAS RWADPDHFAQ RQSCMNTFAS WFGYMPLIHS QMRLDPVLFK DQVSILRKKY RDIERL //