EXT2_BOVIN
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 03-AUG-2022, entry version 120.
DE RecName: Full=Exostosin-2;
DE EC=2.4.1.224 {ECO:0000269|PubMed:9756849};
DE EC=2.4.1.225 {ECO:0000269|PubMed:9756849};
DE AltName: Full=Glucuronosyl-N-acetylglucosaminyl-proteoglycan/N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase;
DE AltName: Full=HS-polymerase;
DE Short=HS-POL;
DE AltName: Full=Multiple exostoses protein 2 homolog;
GN Name=EXT2;
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, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
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).
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. {ECO:0000250|UniProtKB:Q93063}.
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:9756849};
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:0000269|PubMed:9756849};
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 EXT1. Interacts
CC with GALNT5. Interacts with NDST1. {ECO:0000250|UniProtKB:Q93063}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q93063}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q93063}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q93063}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q93063}. Golgi apparatus, cis-Golgi network
CC membrane {ECO:0000250|UniProtKB:Q93063}; Single-pass type II membrane
CC protein {ECO:0000255}. Secreted {ECO:0000269|PubMed:9756849}. Note=The
CC EXT1/EXT2 complex is localized in the Golgi apparatus (By similarity).
CC A soluble form is found in the serum (PubMed:9756849).
CC {ECO:0000250|UniProtKB:Q93063, ECO:0000269|PubMed:9756849}.
CC -!- PTM: The soluble form derives from the membrane form by proteolytic
CC processing.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 47 family.
CC {ECO:0000305}.
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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 PaxDb; O77783; -.
DR PRIDE; O77783; -.
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: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; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of 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:0016757; F:glycosyltransferase activity; IBA:GO_Central.
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:0006024; P:glycosaminoglycan biosynthetic process; IEA:InterPro.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IEA:InterPro.
DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; IDA:UniProtKB.
DR GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR004263; Exostosin.
DR InterPro; IPR027673; Exostosin-2.
DR InterPro; IPR040911; Exostosin_GT47.
DR InterPro; IPR015338; GT64.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR11062; PTHR11062; 1.
DR PANTHER; PTHR11062:SF128; PTHR11062:SF128; 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 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 ACT_SITE 628
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 490
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 517..522
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 538..540
FT /ligand="substrate"
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 569
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 624..628
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 662..673
FT /ligand="substrate"
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 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
