ID EXT1_PONAB Reviewed; 746 AA. AC Q5RBC3; DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 27-MAR-2024, entry version 79. DE RecName: Full=Exostosin-1 {ECO:0000305}; DE EC=2.4.1.225 {ECO:0000250|UniProtKB:Q16394}; DE AltName: Full=N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase {ECO:0000250|UniProtKB:Q16394}; GN Name=EXT1; OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Pongo. OX NCBI_TaxID=9601; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Heart; RG The German cDNA consortium; RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Glycosyltransferase forming with EXT2 the heterodimeric CC heparan sulfate polymerase which catalyzes the elongation of the CC heparan sulfate glycan backbone. Glycan backbone extension consists in CC the alternating transfer of (1->4)-beta-D-GlcA and (1->4)-alpha-D- CC GlcNAc residues from their respective UDP-sugar donors. Both EXT1 and CC EXT2 are required for the full activity of the polymerase since EXT1 CC bears the N-acetylglucosaminyl-proteoglycan 4-beta- CC glucuronosyltransferase activity within the complex while EXT2 carries CC the glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N- CC acetylglucosaminyltransferase activity. Heparan sulfate proteoglycans CC are ubiquitous components of the extracellular matrix and play an CC important role in tissue homeostasis and signaling. CC {ECO:0000250|UniProtKB:Q16394}. 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; Evidence={ECO:0000250|UniProtKB:Q16394}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20909; CC Evidence={ECO:0000250|UniProtKB:Q16394}; CC -!- PATHWAY: Protein modification; protein glycosylation. CC {ECO:0000250|UniProtKB:Q16394}. CC -!- SUBUNIT: Part of the heparan sulfate polymerase, a dimeric complex CC composed of EXT1 and EXT2. Could also form homooligomeric complexes. CC Interacts with NDST1. {ECO:0000250|UniProtKB:Q16394}. CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000250|UniProtKB:Q16394}; Single-pass type II membrane protein CC {ECO:0000255}. Golgi apparatus, cis-Golgi network membrane CC {ECO:0000250|UniProtKB:Q16394}; Single-pass type II membrane protein CC {ECO:0000255}. Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q16394}; Single-pass type II membrane protein CC {ECO:0000255}. Note=The active heparan sulfate polymerase complex CC composed of EXT1 and EXT2 is localized to the Golgi apparatus. If both CC proteins are individually detected in the endoplasmic reticulum, the CC formation of the complex promotes their transport to the Golgi. CC {ECO:0000250|UniProtKB:Q16394}. CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q16394}. CC -!- SIMILARITY: Belongs to the glycosyltransferase 47 family. CC {ECO:0000305}. 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; CR858728; CAH90937.1; -; mRNA. DR RefSeq; NP_001125538.1; NM_001132066.1. DR AlphaFoldDB; Q5RBC3; -. DR SMR; Q5RBC3; -. DR STRING; 9601.ENSPPYP00000021133; -. DR CAZy; GT47; Glycosyltransferase Family 47. DR CAZy; GT64; Glycosyltransferase Family 64. DR GlyCosmos; Q5RBC3; 2 sites, No reported glycans. DR GeneID; 100172450; -. DR KEGG; pon:100172450; -. DR CTD; 2131; -. DR eggNOG; KOG1021; Eukaryota. DR InParanoid; Q5RBC3; -. DR OrthoDB; 1220028at2759; -. DR UniPathway; UPA00378; -. DR Proteomes; UP000001595; Unplaced. DR GO; GO:1902494; C:catalytic complex; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0050508; F:glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity; IEA:UniProtKB-EC. 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:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; ISS:UniProtKB. DR GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway. DR InterPro; IPR004263; Exostosin. DR InterPro; IPR040911; Exostosin_GT47. DR InterPro; IPR015338; GT64. DR InterPro; IPR029044; Nucleotide-diphossugar_trans. DR PANTHER; PTHR48261; ACETYLGLUCOSAMINYLTRANSFERASE; 1. DR PANTHER; PTHR48261:SF2; EXOSTOSIN-1-LIKE; 1. DR Pfam; PF03016; Exostosin; 1. DR Pfam; PF09258; Glyco_transf_64; 1. DR SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1. PE 2: Evidence at transcript level; KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Glycosyltransferase; KW Golgi apparatus; Manganese; Membrane; Metal-binding; Reference proteome; KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix. FT CHAIN 1..746 FT /note="Exostosin-1" FT /id="PRO_0000366931" 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 BINDING 166 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /ligand_part="O(3)-(N-acetyl-alpha-D-glucosaminyl- FT poly[(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D- FT glucosaminyl]-(1->4)-beta-D-glucuronosyl-(1->3)-beta-D- FT galactosyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-xylosyl)- FT L-serine residue" FT /ligand_part_id="ChEBI:CHEBI:132416" FT /evidence="ECO:0000250|UniProtKB:Q16394" FT BINDING 203 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /ligand_part="O(3)-(N-acetyl-alpha-D-glucosaminyl- FT poly[(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D- FT glucosaminyl]-(1->4)-beta-D-glucuronosyl-(1->3)-beta-D- FT galactosyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-xylosyl)- FT L-serine residue" FT /ligand_part_id="ChEBI:CHEBI:132416" FT /evidence="ECO:0000250|UniProtKB:Q16394" FT BINDING 267 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q16394" FT BINDING 269 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q16394" FT BINDING 271 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q16394" FT BINDING 280 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q16394" FT BINDING 300 FT /ligand="a protein" FT /ligand_id="ChEBI:CHEBI:16541" FT /ligand_part="O(3)-(N-acetyl-alpha-D-glucosaminyl- FT poly[(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D- FT glucosaminyl]-(1->4)-beta-D-glucuronosyl-(1->3)-beta-D- FT galactosyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-xylosyl)- FT L-serine residue" FT /ligand_part_id="ChEBI:CHEBI:132416" FT /evidence="ECO:0000250|UniProtKB:Q16394" FT BINDING 319 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q16394" FT BINDING 324 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q16394" FT BINDING 346 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q16394" FT BINDING 349 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q16394" 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:0000250|UniProtKB:Q16394" FT DISULFID 98..103 FT /evidence="ECO:0000250|UniProtKB:Q16394" FT DISULFID 109..152 FT /evidence="ECO:0000250|UniProtKB:Q16394" FT DISULFID 298..312 FT /evidence="ECO:0000250|UniProtKB:Q16394" FT DISULFID 334..355 FT /evidence="ECO:0000250|UniProtKB:Q16394" FT DISULFID 652..704 FT /evidence="ECO:0000250|UniProtKB:Q16394" SQ SEQUENCE 746 AA; 86270 MW; 2BDBFD1396DBA31F CRC64; MQAKKRYFIL LSAGSCLALL FYFGGLQFRA SRSHSRREEH SGRNGLHHPS PDHFWPRFPD ALRPFVPWDQ LENEDSSVHI SPRQKRDANS SIYKGKKCRM ESCFDFTLCK KNGFKVYAYP 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 ATAVPVIVIE GESKVMSSRF LPYDNIITDA VLSLDEDTVL STTEVDFAFT VWRSFPERIV GYPARSHFWD NSKERWGYTS KWTNDYSMVL TGAAIYHKYY HYLYSHYLPA SLKNMVDQLA NCEDILMNFL VSAVTKLPPI KVTQKEQYKE TMMGQTSRAS RWADPDHFAQ RQSCMNTFAS WFGYMPLIHS QMRLDPVLFK DQVSILRKKY RDIERL //