EXT1_HUMAN
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 03-AUG-2022, entry version 211.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 multiple
RT 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., 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 [3]
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 (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 project:
RT 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 products,
RT 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 a
RT 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., 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 [9]
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 [10]
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 [11]
RP VARIANTS EXT1 GLY-280 AND HIS-340.
RA Raskind W.H., Matsushita M., Conrad E.U. III, Wells D.E., Sandell L.J.,
RA Wagner M.J., Houck J.;
RT "Spectrum of EXT1 mutations in hereditary multiple exostoses.";
RL Am. J. Hum. Genet. 59:A280-A280(1996).
RN [12]
RP VARIANT EXT1 LEU-340.
RX PubMed=8981950;
RA Hecht J.T., Hogue D.A., Wang Y., Blanton S.H., Wagner M.J., Strong L.C.,
RA Raskind W.H., Hansen M.F., Wells D.E.;
RT "Hereditary multiple exostoses (EXT): mutational studies of familial EXT1
RT cases and EXT-associated malignancies.";
RL Am. J. Hum. Genet. 60:80-86(1997).
RN [13]
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 hereditary
RT multiple exostoses.";
RL Am. J. Hum. Genet. 61:520-528(1997).
RN [14]
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., Pazzaglia U.E.,
RA Mortier G., Hamel B.C.J., Conrad E.U. III, Matsushita M., Raskind W.H.,
RA Willems P.J.;
RT "Mutations in the EXT1 and EXT2 genes in hereditary multiple exostoses.";
RL Am. J. Hum. Genet. 62:346-354(1998).
RN [15]
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., Wells D.E.,
RA Chapman N., Sandell L.J., Wagner M.J., Houck J.;
RT "Evaluation of locus heterogeneity and EXT1 mutations in 34 families with
RT hereditary multiple exostoses.";
RL Hum. Mutat. 11:231-239(1998).
RN [16]
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., 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 [17]
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., Fan C.,
RA Deng H.-X.;
RT "Mutation analysis of hereditary multiple exostoses in the Chinese.";
RL Hum. Genet. 105:45-50(1999).
RN [18]
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 EXT2
RT in exostosis chondrocytes.";
RL Cell Motil. Cytoskeleton 48:149-162(2001).
RN [19]
RP CHARACTERIZATION OF VARIANTS, AND MUTAGENESIS OF GLN-27; ASP-164; ASN-316;
RP 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., 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 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:11518722,
CC 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 EXT2. Interacts
CC with NDST1. {ECO:0000269|PubMed:10679296, 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 -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DISEASE: Hereditary multiple exostoses 1 (EXT1) [MIM:133700]: 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:10441575, ECO:0000269|PubMed:10480354,
CC ECO:0000269|PubMed:11169766, ECO:0000269|PubMed:8981950,
CC ECO:0000269|PubMed:9326317, ECO:0000269|PubMed:9463333,
CC ECO:0000269|PubMed:9521425, ECO:0000269|Ref.11}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Tricho-rhino-phalangeal syndrome 2 (TRPS2) [MIM:150230]: A
CC syndrome that combines the clinical features of tricho-rhino-phalangeal
CC syndrome type 1 and multiple exostoses type 1. Affected individuals
CC manifest multiple dysmorphic facial features including large, laterally
CC protruding ears, a bulbous nose, an elongated upper lip, as well as
CC sparse scalp hair, winged scapulae, multiple cartilaginous exostoses,
CC redundant skin, and intellectual disability. Note=The gene represented
CC in this entry is involved in disease pathogenesis. A chromosomal
CC aberration resulting in the loss of functional copies of TRPS1 and EXT1
CC has been found in TRPS2 patients.
CC -!- DISEASE: Chondrosarcoma (CHDSA) [MIM:215300]: A malignant neoplasm
CC derived from cartilage cells. Chondrosarcomas range from slow-growing
CC non-metastasizing lesions to highly aggressive metastasizing sarcomas.
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/EXT1ID212.html";
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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 AlphaFoldDB; Q16394; -.
DR SMR; Q16394; -.
DR BioGRID; 108432; 58.
DR CORUM; Q16394; -.
DR IntAct; Q16394; 24.
DR STRING; 9606.ENSP00000367446; -.
DR CAZy; GT47; Glycosyltransferase Family 47.
DR CAZy; GT64; Glycosyltransferase Family 64.
DR GlyGen; Q16394; 2 sites.
DR iPTMnet; Q16394; -.
DR PhosphoSitePlus; Q16394; -.
DR BioMuta; EXT1; -.
DR DMDM; 20141422; -.
DR EPD; Q16394; -.
DR MassIVE; Q16394; -.
DR MaxQB; Q16394; -.
DR PaxDb; Q16394; -.
DR PeptideAtlas; Q16394; -.
DR PRIDE; Q16394; -.
DR ProteomicsDB; 60869; -.
DR Antibodypedia; 26732; 251 antibodies from 30 providers.
DR DNASU; 2131; -.
DR Ensembl; ENST00000378204.7; ENSP00000367446.3; ENSG00000182197.13.
DR GeneID; 2131; -.
DR KEGG; hsa:2131; -.
DR MANE-Select; ENST00000378204.7; ENSP00000367446.3; NM_000127.3; NP_000118.2.
DR UCSC; uc003yok.3; human.
DR CTD; 2131; -.
DR DisGeNET; 2131; -.
DR GeneCards; EXT1; -.
DR GeneReviews; EXT1; -.
DR HGNC; HGNC:3512; EXT1.
DR HPA; ENSG00000182197; Low tissue specificity.
DR MalaCards; EXT1; -.
DR MIM; 133700; phenotype.
DR MIM; 150230; phenotype.
DR MIM; 215300; phenotype.
DR MIM; 608177; gene.
DR neXtProt; NX_Q16394; -.
DR OpenTargets; ENSG00000182197; -.
DR Orphanet; 55880; Chondrosarcoma.
DR Orphanet; 321; Multiple osteochondromas.
DR Orphanet; 502; Trichorhinophalangeal syndrome type 2.
DR PharmGKB; PA27924; -.
DR VEuPathDB; HostDB:ENSG00000182197; -.
DR eggNOG; KOG1021; Eukaryota.
DR GeneTree; ENSGT00940000155321; -.
DR HOGENOM; CLU_013906_4_0_1; -.
DR InParanoid; Q16394; -.
DR OMA; YHRYYNT; -.
DR OrthoDB; 436779at2759; -.
DR PhylomeDB; Q16394; -.
DR TreeFam; TF314231; -.
DR BioCyc; MetaCyc:HS00012-MON; -.
DR BRENDA; 2.4.1.224; 2681.
DR BRENDA; 2.4.1.225; 2681.
DR PathwayCommons; Q16394; -.
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; Q16394; -.
DR SIGNOR; Q16394; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 2131; 80 hits in 1082 CRISPR screens.
DR ChiTaRS; EXT1; human.
DR GeneWiki; EXT1; -.
DR GenomeRNAi; 2131; -.
DR Pharos; Q16394; Tbio.
DR PRO; PR:Q16394; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q16394; protein.
DR Bgee; ENSG00000182197; Expressed in stromal cell of endometrium and 200 other tissues.
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; TAS:ProtInc.
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:0045202; C:synapse; IEA:GOC.
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: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; 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:0019882; P:antigen processing and presentation; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR GO; GO:0071711; P:basement membrane organization; IEA:Ensembl.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0045453; P:bone resorption; IEA:Ensembl.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0060351; P:cartilage development involved in endochondral bone morphogenesis; IEA:Ensembl.
DR GO; GO:0033627; P:cell adhesion mediated by integrin; IEA:Ensembl.
DR GO; GO:0045165; P:cell fate commitment; IEA:Ensembl.
DR GO; GO:0033692; P:cellular polysaccharide biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0098586; P:cellular response to virus; IEA:Ensembl.
DR GO; GO:0003415; P:chondrocyte hypertrophy; IEA:Ensembl.
DR GO; GO:0035988; P:chondrocyte proliferation; IEA:Ensembl.
DR GO; GO:0030204; P:chondroitin sulfate metabolic process; IEA:Ensembl.
DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR GO; GO:1904888; P:cranial skeletal system development; IEA:Ensembl.
DR GO; GO:0070593; P:dendrite self-avoidance; IEA:Ensembl.
DR GO; GO:0036336; P:dendritic cell migration; IEA:Ensembl.
DR GO; GO:0060560; P:developmental growth involved in morphogenesis; IEA:Ensembl.
DR GO; GO:0072498; P:embryonic skeletal joint development; IEA:Ensembl.
DR GO; GO:0003416; P:endochondral bone growth; IEA:Ensembl.
DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl.
DR GO; GO:0007492; P:endoderm development; IEA:Ensembl.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IEA:Ensembl.
DR GO; GO:0042596; P:fear response; IEA:Ensembl.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0042044; P:fluid transport; IEA:Ensembl.
DR GO; GO:0007369; P:gastrulation; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0002067; P:glandular epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0032836; P:glomerular basement membrane development; IEA:Ensembl.
DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0031069; P:hair follicle morphogenesis; IEA:Ensembl.
DR GO; GO:0060047; P:heart contraction; IEA:Ensembl.
DR GO; GO:0003128; P:heart field specification; IEA:Ensembl.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IEA:Ensembl.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; IEA:Ensembl.
DR GO; GO:0097241; P:hematopoietic stem cell migration to bone marrow; IEA:Ensembl.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IDA: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:0002524; P:hypersensitivity; IEA:Ensembl.
DR GO; GO:0050901; P:leukocyte tethering or rolling; IEA:Ensembl.
DR GO; GO:0036022; P:limb joint morphogenesis; IEA:Ensembl.
DR GO; GO:0036339; P:lymphocyte adhesion to endothelial cell of high endothelial venule; IEA:Ensembl.
DR GO; GO:0097021; P:lymphocyte migration into lymphoid organs; IEA:Ensembl.
DR GO; GO:1901706; P:mesenchymal cell differentiation involved in bone development; IEA:Ensembl.
DR GO; GO:0007498; P:mesoderm development; IEA:Ensembl.
DR GO; GO:0061744; P:motor behavior; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; IEA:Ensembl.
DR GO; GO:0014033; P:neural crest cell differentiation; IEA:Ensembl.
DR GO; GO:0021772; P:olfactory bulb development; IEA:Ensembl.
DR GO; GO:0021554; P:optic nerve development; IEA:Ensembl.
DR GO; GO:0001503; P:ossification; IMP:BHF-UCL.
DR GO; GO:0043931; P:ossification involved in bone maturation; IEA:Ensembl.
DR GO; GO:0061974; P:perichondral bone morphogenesis; IEA:Ensembl.
DR GO; GO:0072112; P:podocyte differentiation; IEA:Ensembl.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
DR GO; GO:0065003; P:protein-containing complex assembly; IEA:Ensembl.
DR GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl.
DR GO; GO:0071503; P:response to heparin; IEA:Ensembl.
DR GO; GO:1990823; P:response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0009642; P:response to light intensity; IEA:Ensembl.
DR GO; GO:0048733; P:sebaceous gland development; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR GO; GO:0060506; P:smoothened signaling pathway involved in lung development; IEA:Ensembl.
DR GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR GO; GO:0055078; P:sodium ion homeostasis; IEA:Ensembl.
DR GO; GO:0017145; P:stem cell division; IEA:Ensembl.
DR GO; GO:0062094; P:stomach development; IEA:Ensembl.
DR GO; GO:0051923; P:sulfation; IEA:Ensembl.
DR GO; GO:0060792; P:sweat gland development; IEA:Ensembl.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IEA:Ensembl.
DR GO; GO:0120193; P:tight junction organization; IEA:Ensembl.
DR GO; GO:0071847; P:TNFSF11-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0007033; P:vacuole organization; IEA:Ensembl.
DR GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR GO; GO:0071625; P:vocalization behavior; IEA:Ensembl.
DR GO; GO:0042060; P:wound healing; IEA:Ensembl.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR004263; Exostosin.
DR InterPro; IPR027670; Exostosin-1.
DR InterPro; IPR040911; Exostosin_GT47.
DR InterPro; IPR015338; GT64.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR11062; PTHR11062; 1.
DR PANTHER; PTHR11062:SF97; PTHR11062:SF97; 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 Disease variant; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Glycosyltransferase; Golgi apparatus; Hereditary multiple exostoses;
KW Manganese; Membrane; Metal-binding; Reference proteome; Signal-anchor;
KW Transferase; Transmembrane; Transmembrane helix; Tumor suppressor.
FT CHAIN 1..746
FT /note="Exostosin-1"
FT /id="PRO_0000149648"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..28
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..746
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 654
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 518
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 544..549
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 565..567
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 567
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 595
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 650..654
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 688..701
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 330
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 652..704
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT VARIANT 27
FT /note="Q -> K (in EXT1; no loss of activity)"
FT /id="VAR_012815"
FT VARIANT 164
FT /note="D -> H (in EXT1; loss of activity)"
FT /evidence="ECO:0000269|PubMed:10441575"
FT /id="VAR_012816"
FT VARIANT 215..222
FT /note="MLAKASIS -> I (in isolated osteochondroma; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:11169766"
FT /id="VAR_012818"
FT VARIANT 215..221
FT /note="Missing (in EXT1)"
FT /id="VAR_012817"
FT VARIANT 235..239
FT /note="Missing (in multiple osteochondromas)"
FT /evidence="ECO:0000269|PubMed:10441575"
FT /id="VAR_012819"
FT VARIANT 280
FT /note="R -> G (in EXT1; loss of activity;
FT dbSNP:rs1554601483)"
FT /evidence="ECO:0000269|PubMed:9463333,
FT ECO:0000269|PubMed:9521425, ECO:0000269|Ref.11"
FT /id="VAR_002370"
FT VARIANT 280
FT /note="R -> S (in EXT1; loss of activity;
FT dbSNP:rs1563659325)"
FT /evidence="ECO:0000269|PubMed:9521425"
FT /id="VAR_002371"
FT VARIANT 316
FT /note="N -> S (in chondrosarcoma; no loss of activity)"
FT /evidence="ECO:0000269|PubMed:10441575"
FT /id="VAR_012820"
FT VARIANT 339
FT /note="G -> D (in EXT1; loss of activity;
FT dbSNP:rs119103288)"
FT /evidence="ECO:0000269|PubMed:9326317"
FT /id="VAR_002372"
FT VARIANT 340
FT /note="R -> C (in EXT1; loss of activity; still able to
FT form an oligomeric complex; dbSNP:rs119103290)"
FT /evidence="ECO:0000269|PubMed:9326317"
FT /id="VAR_002373"
FT VARIANT 340
FT /note="R -> H (in EXT1; loss of activity;
FT dbSNP:rs119103287)"
FT /evidence="ECO:0000269|PubMed:9521425, ECO:0000269|Ref.11"
FT /id="VAR_002374"
FT VARIANT 340
FT /note="R -> L (in EXT1; loss of activity;
FT dbSNP:rs119103287)"
FT /evidence="ECO:0000269|PubMed:8981950"
FT /id="VAR_002375"
FT VARIANT 340
FT /note="R -> S (in EXT1; loss of activity)"
FT /evidence="ECO:0000269|PubMed:9463333"
FT /id="VAR_002376"
FT VARIANT 486
FT /note="A -> V (in EXT1; no loss of activity;
FT dbSNP:rs188859975)"
FT /evidence="ECO:0000269|PubMed:10480354"
FT /id="VAR_012821"
FT VARIANT 496
FT /note="P -> L (in EXT1; no loss of activity)"
FT /evidence="ECO:0000269|PubMed:10480354"
FT /id="VAR_012822"
FT VARIANT 627
FT /note="Missing (in EXT1; loss of activity)"
FT /evidence="ECO:0000269|PubMed:9521425"
FT /id="VAR_002377"
FT MUTAGEN 27
FT /note="Q->A,P: No effect on heparan-sulfate biosynthesis."
FT /evidence="ECO:0000269|PubMed:11391482"
FT MUTAGEN 27
FT /note="Missing: No effect on heparan-sulfate biosynthesis."
FT /evidence="ECO:0000269|PubMed:11391482"
FT MUTAGEN 164
FT /note="D->E: Abolishes heparan-sulfate biosynthesis."
FT /evidence="ECO:0000269|PubMed:11391482"
FT MUTAGEN 164
FT /note="Missing: Abolishes heparan-sulfate biosynthesis."
FT /evidence="ECO:0000269|PubMed:11391482"
FT MUTAGEN 316
FT /note="N->A: No effect on heparan-sulfate biosynthesis."
FT /evidence="ECO:0000269|PubMed:11391482"
FT MUTAGEN 316
FT /note="Missing: No effect on heparan-sulfate biosynthesis."
FT /evidence="ECO:0000269|PubMed:11391482"
FT MUTAGEN 486
FT /note="A->H: No effect on heparan-sulfate biosynthesis."
FT /evidence="ECO:0000269|PubMed:11391482"
FT MUTAGEN 486
FT /note="Missing: No effect on heparan-sulfate biosynthesis."
FT /evidence="ECO:0000269|PubMed:11391482"
FT MUTAGEN 496
FT /note="P->H: No effect on heparan-sulfate biosynthesis."
FT /evidence="ECO:0000269|PubMed:11391482"
FT MUTAGEN 496
FT /note="Missing: No effect on heparan-sulfate biosynthesis."
FT /evidence="ECO:0000269|PubMed:11391482"
FT CONFLICT 60..61
FT /note="DA -> EP (in Ref. 1 and 3)"
FT /evidence="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
