ID   EXT1_CRIGR              Reviewed;         746 AA.
AC   Q9JK82;
DT   27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   27-MAR-2024, entry version 106.
DE   RecName: Full=Exostosin-1 {ECO:0000305};
DE            EC=2.4.1.225 {ECO:0000250|UniProtKB:Q16394};
DE   AltName: Full=Heparan sulfate copolymerase {ECO:0000303|PubMed:10864928};
DE   AltName: Full=N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase {ECO:0000250|UniProtKB:Q16394};
GN   Name=EXT1 {ECO:0000303|PubMed:10864928};
OS   Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC   Cricetidae; Cricetinae; Cricetulus.
OX   NCBI_TaxID=10029;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND MUTAGENESIS OF GLY-268; CYS-298; ARG-341;
RP   SER-344; ARG-346 AND GLU-349.
RX   PubMed=10864928; DOI=10.1074/jbc.m002990200;
RA   Wei G., Bai X., Gabb M.M.G., Bame K.J., Koshy T.I., Spear P.G., Esko J.D.;
RT   "Location of the glucuronosyltransferase domain in the heparan sulfate
RT   copolymerase EXT1 by analysis of Chinese hamster ovary cell mutants.";
RL   J. Biol. Chem. 275:27733-27740(2000).
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}.
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DR   EMBL; AF252858; AAF71276.1; -; mRNA.
DR   RefSeq; NP_001233696.1; NM_001246767.1.
DR   AlphaFoldDB; Q9JK82; -.
DR   SMR; Q9JK82; -.
DR   CAZy; GT47; Glycosyltransferase Family 47.
DR   CAZy; GT64; Glycosyltransferase Family 64.
DR   GlyCosmos; Q9JK82; 2 sites, No reported glycans.
DR   PaxDb; 10029-NP_001233696-1; -.
DR   Ensembl; ENSCGRT00001021710.1; ENSCGRP00001017466.1; ENSCGRG00001017502.1.
DR   Ensembl; ENSCGRT00015042847; ENSCGRP00015035171; ENSCGRG00015026401.
DR   GeneID; 100689334; -.
DR   KEGG; cge:100689334; -.
DR   CTD; 2131; -.
DR   eggNOG; KOG1021; Eukaryota.
DR   GeneTree; ENSGT00940000155321; -.
DR   OrthoDB; 1220028at2759; -.
DR   UniPathway; UPA00378; -.
DR   Proteomes; UP000694386; Unplaced.
DR   Proteomes; UP001108280; Chromosome 10.
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; ISS:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR   GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0045202; C:synapse; IEA:GOC.
DR   GO; GO:0050508; F:glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity; ISS:UniProtKB.
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; IEA:Ensembl.
DR   GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
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: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: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; ISS:UniProtKB.
DR   GO; GO:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; ISS:UniProtKB.
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-level 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: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: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   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   Disulfide bond; Endoplasmic reticulum; Glycoprotein; Glycosyltransferase;
KW   Golgi apparatus; Manganese; Membrane; Metal-binding; Signal-anchor;
KW   Transferase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..746
FT                   /note="Exostosin-1"
FT                   /id="PRO_0000149647"
FT   TOPO_DOM        1..5
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        6..26
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        27..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"
FT   MUTAGEN         268
FT                   /note="G->E: Reduced GlcA transferase activity."
FT                   /evidence="ECO:0000269|PubMed:10864928"
FT   MUTAGEN         298
FT                   /note="C->Y: Reduced GlcA transferase activity."
FT                   /evidence="ECO:0000269|PubMed:10864928"
FT   MUTAGEN         341
FT                   /note="R->K: Reduced GlcA transferase activity."
FT                   /evidence="ECO:0000269|PubMed:10864928"
FT   MUTAGEN         344
FT                   /note="S->F: Reduced GlcA transferase activity."
FT                   /evidence="ECO:0000269|PubMed:10864928"
FT   MUTAGEN         346
FT                   /note="R->K: Reduced GlcA transferase activity."
FT                   /evidence="ECO:0000269|PubMed:10864928"
FT   MUTAGEN         349
FT                   /note="E->K: Reduced GlcA transferase activity."
FT                   /evidence="ECO:0000269|PubMed:10864928"
SQ   SEQUENCE   746 AA;  86189 MW;  C3697B4A421DA4F2 CRC64;
     MQAKKRYFIL LSAGSCLALL FYFGGVQFRA SRSHSRREEH SGRNGLHQPS PDHFWPRFAD
     ALHPFFPWDQ LENEDSGVHV SPRQKRDANS SVYKGKKCRM ESCFDFALCK KNGFKVYVYP
     QQKGEKIAES YQNILAAIEG SRFYTSDPSQ ACLFVLSLDT LDRDQLSPQY VHNLRSKVQS
     LHLWNNGRNH LIFNLYSGTW PDYTEDVGFD IGQAMLAKAS ISTENFRPNF DVSIPLFSKD
     HPRTGGERGF LKFNTIPPLR KYMLVFKGKR YLTGIGSDTR NALYHVHNGE DVLLLTTCKH
     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 VWQSFPERIV GYPARSHFWD
     NSKERWGYTS KWTNDYSMVL TGAAIYHKYY HYLYTHYLPA SLKNMVDQLA NCEDILMNFL
     VSAVTKLPPI KVTQKKQYKE TMMGQTSRAS RWADPDHFAQ RQSCMNTFAS WFGYMPLIHS
     QMRLDPVLFK DQVSILRKKY RDIERL
//