EXT1_CRIGR
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 03-AUG-2022, entry version 100.
DE RecName: Full=Exostosin-1;
DE EC=2.4.1.224;
DE EC=2.4.1.225;
DE AltName: Full=Heparan sulfate copolymerase;
DE AltName: Full=Multiple exostoses protein 1 homolog;
GN Name=EXT1;
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 CHARACTERIZATION OF MUTANTS GLY-268;
RP CYS-298; ARG-341; 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 required for the biosynthesis of heparan-
CC sulfate. The EXT1/EXT2 complex possesses substantially higher
CC glycosyltransferase activity than EXT1 or EXT2 alone. Required for the
CC exosomal release of SDCBP, CD63 and syndecan (By similarity).
CC {ECO:0000250|UniProtKB:Q16394}.
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;
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;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9ES89};
CC Note=Manganese. Divalent cations. {ECO:0000250|UniProtKB:Q9ES89};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBUNIT: Forms a homo/heterooligomeric complex with EXT2. Interacts
CC with NDST1. {ECO:0000250|UniProtKB:Q16394}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q16394}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q16394}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q16394}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q16394}. Golgi apparatus, cis-Golgi network
CC membrane {ECO:0000250|UniProtKB:Q16394}; Single-pass type II membrane
CC protein {ECO:0000255}. Note=The EXT1/EXT2 complex is localized in the
CC Golgi apparatus. {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 STRING; 10029.NP_001233696.1; -.
DR CAZy; GT47; Glycosyltransferase Family 47.
DR CAZy; GT64; Glycosyltransferase Family 64.
DR Ensembl; ENSCGRT00001021710; ENSCGRP00001017466; ENSCGRG00001017502.
DR GeneID; 100689334; -.
DR KEGG; cge:100689334; -.
DR CTD; 2131; -.
DR eggNOG; KOG1021; Eukaryota.
DR GeneTree; ENSGT00940000155321; -.
DR OrthoDB; 789556at2759; -.
DR UniPathway; UPA00378; -.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB.
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; IEA:Ensembl.
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 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 Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR004263; Exostosin.
DR InterPro; IPR027670; Exostosin-1.
DR InterPro; IPR040911; Exostosin_GT47.
DR InterPro; IPR015338; GT64.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR11062; PTHR11062; 1.
DR PANTHER; PTHR11062:SF97; PTHR11062:SF97; 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 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 ACT_SITE 654
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 518
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 544..549
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 565..567
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 567
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 595
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 650..654
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 688..701
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
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:0000255"
FT DISULFID 652..704
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT MUTAGEN 268
FT /note="G->E: Reduced GlcA transferase activity."
FT MUTAGEN 298
FT /note="C->Y: Reduced GlcA transferase activity."
FT MUTAGEN 341
FT /note="R->K: Reduced GlcA transferase activity."
FT MUTAGEN 344
FT /note="S->F: Reduced GlcA transferase activity."
FT MUTAGEN 346
FT /note="R->K: Reduced GlcA transferase activity."
FT MUTAGEN 349
FT /note="E->K: Reduced GlcA transferase activity."
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
