ID EXT2_BOVIN Reviewed; 718 AA. AC O77783; DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 27-MAR-2024, entry version 126. DE RecName: Full=Exostosin-2 {ECO:0000305}; DE EC=2.4.1.224 {ECO:0000269|PubMed:10639137, ECO:0000269|PubMed:9756849}; DE AltName: Full=Glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase {ECO:0000305|PubMed:9756849}; DE AltName: Full=HS-polymerase {ECO:0000303|PubMed:9756849}; DE Short=HS-POL {ECO:0000303|PubMed:9756849}; GN Name=EXT2 {ECO:0000303|PubMed:9756849}; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 129-147; 167-179; 485-494 RP AND 570-577, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, RP AND PTM. RC TISSUE=Lung; RX PubMed=9756849; DOI=10.1074/jbc.273.41.26265; RA Lind T., Tufaro F., McCormick C., Lindahl U., Lidholt K.; RT "The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases RT required for the biosynthesis of heparan sulfate."; RL J. Biol. Chem. 273:26265-26268(1998). RN [2] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=10639137; DOI=10.1073/pnas.97.2.668; RA McCormick C., Duncan G., Goutsos K.T., Tufaro F.; RT "The putative tumor suppressors EXT1 and EXT2 form a stable complex that RT accumulates in the Golgi apparatus and catalyzes the synthesis of heparan RT sulfate."; RL Proc. Natl. Acad. Sci. U.S.A. 97:668-673(2000). CC -!- FUNCTION: Glycosyltransferase forming with EXT1 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 (PubMed:9756849, CC PubMed:10639137). Both EXT1 and EXT2 are required for the full activity CC of the polymerase since EXT1 bears the N-acetylglucosaminyl- CC proteoglycan 4-beta-glucuronosyltransferase activity within the complex CC while EXT2 carries the glucuronosyl-N-acetylglucosaminyl-proteoglycan CC 4-alpha-N-acetylglucosaminyltransferase activity (By similarity). CC Heparan sulfate proteoglycans are ubiquitous components of the CC extracellular matrix and play an important role in tissue homeostasis CC and signaling (By similarity). {ECO:0000250|UniProtKB:Q93063, CC ECO:0000269|PubMed:10639137, ECO:0000269|PubMed:9756849}. 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; Evidence={ECO:0000269|PubMed:10639137, CC ECO:0000269|PubMed:9756849}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16214; CC Evidence={ECO:0000305|PubMed:9756849}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:Q93063}; CC -!- PATHWAY: Protein modification; protein glycosylation. CC {ECO:0000269|PubMed:10639137, ECO:0000269|PubMed:9756849}. 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. Interacts with GALNT5. CC {ECO:0000250|UniProtKB:Q93063}. CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000250|UniProtKB:Q93063}; Single-pass type II membrane protein CC {ECO:0000255}. Golgi apparatus, cis-Golgi network membrane CC {ECO:0000250|UniProtKB:Q93063}; Single-pass type II membrane protein CC {ECO:0000255}. Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q93063}; Single-pass type II membrane protein CC {ECO:0000255}. Secreted {ECO:0000269|PubMed:9756849}. Note=The active CC heparan sulfate polymerase complex composed of EXT1 and EXT2 is CC localized in the Golgi apparatus though both proteins are also detected CC in the endoplasmic reticulum (By similarity). A soluble form is found CC in the serum (PubMed:9756849). {ECO:0000250|UniProtKB:Q93063, CC ECO:0000269|PubMed:9756849}. CC -!- PTM: A soluble form is generated by proteolytic processing. CC {ECO:0000269|PubMed:9756849}. CC -!- PTM: N-glycosylated at Asn-637. {ECO:0000250|UniProtKB:Q93063}. 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; AF089748; AAC35386.1; -; mRNA. DR AlphaFoldDB; O77783; -. DR SMR; O77783; -. DR STRING; 9913.ENSBTAP00000026177; -. DR CAZy; GT47; Glycosyltransferase Family 47. DR CAZy; GT64; Glycosyltransferase Family 64. DR GlyCosmos; O77783; 2 sites, No reported glycans. DR PaxDb; 9913-ENSBTAP00000026177; -. DR eggNOG; KOG1022; Eukaryota. DR InParanoid; O77783; -. DR BRENDA; 2.4.1.224; 908. DR BRENDA; 2.4.1.225; 908. DR UniPathway; UPA00378; -. DR Proteomes; UP000009136; 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:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; 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:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0050509; F:N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity; IDA:UniProtKB. DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IDA:UniProtKB. DR GO; GO:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; ISS:UniProtKB. DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; IDA: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 1: Evidence at protein level; KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; KW Glycoprotein; Glycosyltransferase; Golgi apparatus; Manganese; Membrane; KW Metal-binding; Reference proteome; Secreted; Signal-anchor; Transferase; KW Transmembrane; Transmembrane helix. FT CHAIN 1..718 FT /note="Exostosin-2" FT /id="PRO_0000149650" 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:0000250|UniProtKB:Q93063" FT BINDING 465 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q93063" 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:0000250|UniProtKB:Q93063" 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:0000250|UniProtKB:Q93063" 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:0000250|UniProtKB:Q93063" 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:0000250|UniProtKB:Q93063" 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:0000250|UniProtKB:Q9ES89" 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:0000250|UniProtKB:Q93063" 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:0000250|UniProtKB:Q93063" 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:0000250|UniProtKB:Q93063" 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:0000250|UniProtKB:Q93063" 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:0000255" FT DISULFID 85..90 FT /evidence="ECO:0000250|UniProtKB:Q93063" FT DISULFID 96..151 FT /evidence="ECO:0000250|UniProtKB:Q93063" FT DISULFID 286..300 FT /evidence="ECO:0000250|UniProtKB:Q93063" FT DISULFID 318..339 FT /evidence="ECO:0000250|UniProtKB:Q93063" FT DISULFID 626..676 FT /evidence="ECO:0000250|UniProtKB:Q9ES89" SQ SEQUENCE 718 AA; 81887 MW; D6C18AC9C7AAD971 CRC64; MCASVKYNIR GPALIPRMKT KHRIYYITLF SIVLLGLIAT GMFQFWPHSI ESSGDWSVEK RTGRDVPLVR LPADSPVPER GDLSCRMHTC FDVYRCGFNP KNKIKVYIYP LKKYVGEAGV PVSSTISREY NELLTAISDS DYYTDDVTRA CLFVPSIDLL NQNSLRVKET AQALAQLSRW DRGTNHLLFN MLPGGPPDYN TALDVPRDRA LLAGGGFSTW TYRQGYDVSI PVYSPLSAEV DLPEKGPGPR RYFLLSSQVA LHPEYREDLA ALQARHGEAV LVLDKCSNLS EGVPAARRRC HQQQAFDYPQ VLQEATFCMV LRGARLGQAV LSDVLRAGCV PVIIADSYVL PFSEVLDWKR ASVVVPEEKM SDVYSILQSI PRRQIEEMQR QARWFWEAYF QSIKAIALAT LQIINDRIYP YAAISYEDWN 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 //