PubMed:23395820
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/23395820","sourcedb":"PubMed","sourceid":"23395820","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/23395820","text":"EXTL2, a member of the EXT family of tumor suppressors, controls glycosaminoglycan biosynthesis in a xylose kinase-dependent manner.\nMutant alleles of EXT1 or EXT2, two members of the EXT gene family, are causative agents in hereditary multiple exostoses, and their gene products function together as a polymerase in the biosynthesis of heparan sulfate. EXTL2, one of three EXT-like genes in the human genome that are homologous to EXT1 and EXT2, encodes a transferase that adds not only GlcNAc but also N-acetylgalactosamine to the glycosaminoglycan (GAG)-protein linkage region via an α1,4-linkage. However, both the role of EXTL2 in the biosynthesis of GAGs and the biological significance of EXTL2 remain unclear. Here we show that EXTL2 transfers a GlcNAc residue to the tetrasaccharide linkage region that is phosphorylated by a xylose kinase 1 (FAM20B) and thereby terminates chain elongation. We isolated an oligosaccharide from the mouse liver, which was not detected in EXTL2 knock-out mice. Based on structural analysis by a combination of glycosidase digestion and 500-MHz (1)H NMR spectroscopy, the oligosaccharide was found to be GlcNAcα1-4GlcUAβ1-3Galβ1-3Galβ1-4Xyl(2-O-phosphate), which was considered to be a biosynthetic intermediate of an immature GAG chain. Indeed, EXTL2 specifically transferred a GlcNAc residue to a phosphorylated linkage tetrasaccharide, GlcUAβ1-3Galβ1-3Galβ1-4Xyl(2-O-phosphate). Remarkably, the phosphorylated linkage pentasaccharide generated by EXTL2 was not used as an acceptor for heparan sulfate or chondroitin sulfate polymerases. Moreover, production of GAGs was significantly higher in EXTL2 knock-out mice than in wild-type mice. These results indicate that EXTL2 functions to suppress GAG biosynthesis that is enhanced by a xylose kinase and that the EXTL2-dependent mechanism that regulates GAG biosynthesis might be a \"quality control system\" for proteoglycans.","tracks":[{"project":"ngly1-sample4","denotations":[{"id":"T1","span":{"begin":488,"end":494},"obj":"chem:24139"},{"id":"T2","span":{"begin":754,"end":760},"obj":"chem:24139"},{"id":"T3","span":{"begin":1144,"end":1152},"obj":"chem:24139"},{"id":"T4","span":{"begin":1319,"end":1325},"obj":"chem:24139"}],"attributes":[{"subj":"T1","pred":"source","obj":"ngly1-sample4"},{"subj":"T2","pred":"source","obj":"ngly1-sample4"},{"subj":"T3","pred":"source","obj":"ngly1-sample4"},{"subj":"T4","pred":"source","obj":"ngly1-sample4"}]},{"project":"GlyCosmos6-Glycan-Motif-Image","denotations":[{"id":"T1","span":{"begin":504,"end":525},"obj":"Glycan_Motif"},{"id":"T2","span":{"begin":1547,"end":1558},"obj":"Glycan_Motif"}],"attributes":[{"id":"A1","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G27025MB"},{"id":"A2","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G43702JT"},{"subj":"T1","pred":"source","obj":"GlyCosmos6-Glycan-Motif-Image"},{"subj":"T2","pred":"source","obj":"GlyCosmos6-Glycan-Motif-Image"}]},{"project":"Glycosmos6-GlycoEpitope","denotations":[{"id":"T1","span":{"begin":337,"end":352},"obj":"GlycoEpitope"},{"id":"T2","span":{"begin":1528,"end":1543},"obj":"GlycoEpitope"},{"id":"T3","span":{"begin":1547,"end":1558},"obj":"GlycoEpitope"}],"attributes":[{"id":"A1","pred":"glyco_epitope_db_id","subj":"T1","obj":"http://www.glycoepitope.jp/epitopes/EP0086"},{"id":"A2","pred":"glyco_epitope_db_id","subj":"T2","obj":"http://www.glycoepitope.jp/epitopes/EP0086"},{"id":"A3","pred":"glyco_epitope_db_id","subj":"T3","obj":"http://www.glycoepitope.jp/epitopes/EP0081"},{"subj":"T1","pred":"source","obj":"Glycosmos6-GlycoEpitope"},{"subj":"T2","pred":"source","obj":"Glycosmos6-GlycoEpitope"},{"subj":"T3","pred":"source","obj":"Glycosmos6-GlycoEpitope"}]},{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":132},"obj":"Sentence"},{"id":"T2","span":{"begin":133,"end":353},"obj":"Sentence"},{"id":"T3","span":{"begin":354,"end":600},"obj":"Sentence"},{"id":"T4","span":{"begin":601,"end":717},"obj":"Sentence"},{"id":"T5","span":{"begin":718,"end":900},"obj":"Sentence"},{"id":"T6","span":{"begin":901,"end":1001},"obj":"Sentence"},{"id":"T7","span":{"begin":1002,"end":1277},"obj":"Sentence"},{"id":"T8","span":{"begin":1278,"end":1421},"obj":"Sentence"},{"id":"T9","span":{"begin":1422,"end":1579},"obj":"Sentence"},{"id":"T10","span":{"begin":1580,"end":1681},"obj":"Sentence"},{"id":"T11","span":{"begin":1682,"end":1916},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"},{"subj":"T11","pred":"source","obj":"sentences"}]},{"project":"GlyCosmos6-Glycan-Motif-Structure","denotations":[{"id":"T1","span":{"begin":504,"end":525},"obj":"https://glytoucan.org/Structures/Glycans/G27025MB"},{"id":"T2","span":{"begin":1547,"end":1558},"obj":"https://glytoucan.org/Structures/Glycans/G43702JT"}],"attributes":[{"subj":"T1","pred":"source","obj":"GlyCosmos6-Glycan-Motif-Structure"},{"subj":"T2","pred":"source","obj":"GlyCosmos6-Glycan-Motif-Structure"}]},{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":947,"end":952},"obj":"http://purl.obolibrary.org/obo/MAT_0000097"}],"attributes":[{"subj":"T1","pred":"source","obj":"Glycosmos6-MAT"}]},{"project":"Allie","denotations":[{"id":"SS1_23395820_2_0","span":{"begin":533,"end":550},"obj":"expanded"},{"id":"SS2_23395820_2_0","span":{"begin":552,"end":555},"obj":"abbr"}],"relations":[{"id":"AE1_23395820_2_0","pred":"abbreviatedTo","subj":"SS1_23395820_2_0","obj":"SS2_23395820_2_0"}],"attributes":[{"subj":"SS1_23395820_2_0","pred":"source","obj":"Allie"},{"subj":"SS2_23395820_2_0","pred":"source","obj":"Allie"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":236,"end":254},"obj":"HP_0002762"},{"id":"T2","span":{"begin":245,"end":254},"obj":"HP_0100777"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"}]},{"project":"NGLY1-deficiency","denotations":[{"id":"PD-NGLY1-deficiency-B_T1","span":{"begin":488,"end":494},"obj":"chem:24139"},{"id":"PD-NGLY1-deficiency-B_T2","span":{"begin":754,"end":760},"obj":"chem:24139"},{"id":"PD-NGLY1-deficiency-B_T3","span":{"begin":1319,"end":1325},"obj":"chem:24139"}],"namespaces":[{"prefix":"hgnc","uri":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:"},{"prefix":"omim","uri":"https://www.omim.org/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