EXT2_CAEEL
ID EXT2_CAEEL Reviewed; 814 AA.
AC O01705; O17920;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Exostosin-2 homolog {ECO:0000305};
DE EC=2.4.1.223 {ECO:0000269|PubMed:11121397, ECO:0000269|PubMed:17237233};
DE EC=2.4.1.224 {ECO:0000269|PubMed:11121397, ECO:0000269|PubMed:17237233};
DE EC=2.4.1.225 {ECO:0000269|PubMed:17237233};
DE AltName: Full=Glucuronyl-galactosyl-proteoglycan 4-alpha-N- acetylglucosaminyltransferase {ECO:0000305|PubMed:11121397};
DE Short=GlcNAc transferase I {ECO:0000303|PubMed:11121397};
DE Short=GlcNAcT-I {ECO:0000303|PubMed:17237233};
DE AltName: Full=Glucuronyl-galactosyl-proteoglycan/Glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase;
DE Short=GlcAT-II {ECO:0000303|PubMed:17237233};
DE Short=GlcNAc transferase II {ECO:0000303|PubMed:17237233};
DE Short=GlcNAcT-II {ECO:0000303|PubMed:17237233};
DE Short=Glucuronyl transferase II {ECO:0000303|PubMed:17237233};
DE AltName: Full=Multiple exostoses homolog 2;
GN Name=rib-2; ORFNames=K01G5.6;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=9110175; DOI=10.1101/gr.7.4.359;
RA Clines G.A., Ashley J.A., Shah S., Lovett M.;
RT "The structure of the human multiple exostoses 2 gene and characterization
RT of homologs in mouse and Caenorhabditis elegans.";
RL Genome Res. 7:359-367(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11121397; DOI=10.1074/jbc.c000835200;
RA Kitagawa H., Egusa N., Tamura J., Kusche-Gullberg M., Lindahl U.,
RA Sugahara K.;
RT "rib-2, a Caenorhabditis elegans homolog of the human tumor suppressor EXT
RT genes encodes a novel alpha1,4-N-acetylglucosaminyltransferase involved in
RT the biosynthetic initiation and elongation of heparan sulfate.";
RL J. Biol. Chem. 276:4834-4838(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [4]
RP FUNCTION.
RX PubMed=16828468; DOI=10.1016/j.ydbio.2006.06.008;
RA Franks D.M., Izumikawa T., Kitagawa H., Sugahara K., Okkema P.G.;
RT "C. elegans pharyngeal morphogenesis requires both de novo synthesis of
RT pyrimidines and synthesis of heparan sulfate proteoglycans.";
RL Dev. Biol. 296:409-420(2006).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, INTERACTION
RP WITH RIB-1, AND DISRUPTION PHENOTYPE.
RX PubMed=17237233; DOI=10.1074/jbc.m611107200;
RA Kitagawa H., Izumikawa T., Mizuguchi S., Dejima K., Nomura K.H., Egusa N.,
RA Taniguchi F., Tamura J., Gengyo-Ando K., Mitani S., Nomura K., Sugahara K.;
RT "Expression of rib-1, a Caenorhabditis elegans homolog of the human tumor
RT suppressor EXT genes, is indispensable for heparan sulfate synthesis and
RT embryonic morphogenesis.";
RL J. Biol. Chem. 282:8533-8544(2007).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24052309; DOI=10.1126/science.1242528;
RA Pedersen M.E., Snieckute G., Kagias K., Nehammer C., Multhaupt H.A.,
RA Couchman J.R., Pocock R.;
RT "An epidermal microRNA regulates neuronal migration through control of the
RT cellular glycosylation state.";
RL Science 341:1404-1408(2013).
CC -!- FUNCTION: Glycosyltransferase required for the biosynthesis of heparan
CC sulfate (PubMed:11121397, PubMed:16828468, PubMed:17237233). Initiates
CC heparan sulfate synthesis by transferring GlcNAc to the (GlcA-Gal-Gal-
CC Xyl-)Ser core linker (GlcNAcT-I activity) (PubMed:11121397). In
CC association with rib-1, is also responsible for the alternating
CC addition of beta-1-4-linked glucuronic acid (GlcA) and alpha-1-4-linked
CC N-acetylglucosamine (GlcNAc) units to nascent heparan sulfate chains
CC (GlcNAcT-II and GlcAT-II activities) (PubMed:11121397,
CC PubMed:17237233). Required for normal ventral epidermal enclosure
CC during the early stages of embryonic development (PubMed:17237233). In
CC addition, involved in the elongation of the pharyngeal isthmus during
CC the later stages of embryonic development (PubMed:16828468). Involved
CC in the directed migration of hermaphrodite-specific neurons
CC (PubMed:17237233, PubMed:24052309). {ECO:0000269|PubMed:11121397,
CC ECO:0000269|PubMed:16828468, ECO:0000269|PubMed:17237233,
CC ECO:0000269|PubMed:24052309}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-(beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-
CC beta-D-Xyl)-L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-
CC O-(alpha-D-GlcNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-
CC Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + H(+) + UDP;
CC Xref=Rhea:RHEA:16221, Rhea:RHEA-COMP:12573, Rhea:RHEA-COMP:12574,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:132093, ChEBI:CHEBI:132104; EC=2.4.1.223;
CC Evidence={ECO:0000269|PubMed:11121397, ECO:0000269|PubMed:17237233};
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:11121397,
CC ECO:0000269|PubMed:17237233};
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:17237233};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9ES89};
CC -!- ACTIVITY REGULATION: Binding to rib-1 is required for GlcAT-II activity
CC and for increasing GlcNAc-II activity in vitro.
CC {ECO:0000269|PubMed:17237233}.
CC -!- PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
CC {ECO:0000269|PubMed:11121397, ECO:0000269|PubMed:17237233}.
CC -!- SUBUNIT: Interacts with rib-1. {ECO:0000269|PubMed:17237233}.
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}.
CC -!- DISRUPTION PHENOTYPE: Mutant embryos are arrested at the 1-fold stage
CC due to a failure in epidermal enclosure (PubMed:17237233). RNAi-
CC mediated knockdown results in the failure of hermaphrodite-specific
CC neurons to migrate to their correct position and in a defect in axonal
CC guidance (PubMed:24052309). {ECO:0000269|PubMed:17237233,
CC ECO:0000269|PubMed:24052309}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 47 family.
CC {ECO:0000305}.
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DR EMBL; U94835; AAC47510.1; -; mRNA.
DR EMBL; AB077851; BAB83878.1; -; mRNA.
DR EMBL; Z92803; CAB07245.1; -; Genomic_DNA.
DR PIR; T23200; T23200.
DR RefSeq; NP_499368.1; NM_066967.6.
DR AlphaFoldDB; O01705; -.
DR SMR; O01705; -.
DR BioGRID; 41689; 1.
DR STRING; 6239.K01G5.6; -.
DR CAZy; GT47; Glycosyltransferase Family 47.
DR CAZy; GT64; Glycosyltransferase Family 64.
DR EPD; O01705; -.
DR PaxDb; O01705; -.
DR EnsemblMetazoa; K01G5.6.1; K01G5.6.1; WBGene00004361.
DR GeneID; 176502; -.
DR KEGG; cel:CELE_K01G5.6; -.
DR UCSC; K01G5.6; c. elegans.
DR CTD; 176502; -.
DR WormBase; K01G5.6; CE16196; WBGene00004361; rib-2.
DR eggNOG; KOG2264; Eukaryota.
DR GeneTree; ENSGT00940000156692; -.
DR HOGENOM; CLU_013906_3_0_1; -.
DR InParanoid; O01705; -.
DR OMA; WDRIETE; -.
DR OrthoDB; 789556at2759; -.
DR PhylomeDB; O01705; -.
DR UniPathway; UPA00756; -.
DR PRO; PR:O01705; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00004361; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-KW.
DR GO; GO:0032991; C:protein-containing complex; IDA:WormBase.
DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; IDA:WormBase.
DR GO; GO:0019899; F:enzyme binding; IPI:WormBase.
DR GO; GO:0050508; F:glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0001888; F:glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0016757; F:glycosyltransferase activity; IBA:GO_Central.
DR GO; GO:0042328; F:heparan sulfate N-acetylglucosaminyltransferase activity; IDA:WormBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050509; F:N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0048598; P:embryonic morphogenesis; IMP:WormBase.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IDA:WormBase.
DR GO; GO:0060465; P:pharynx development; IMP:WormBase.
DR GO; GO:0006486; P:protein glycosylation; IEA:InterPro.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR004263; Exostosin.
DR InterPro; IPR040911; Exostosin_GT47.
DR InterPro; IPR015338; GT64.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR11062; PTHR11062; 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; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..814
FT /note="Exostosin-2 homolog"
FT /id="PRO_0000149663"
FT TOPO_DOM 1..14
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 15..35
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 36..814
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 728
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 595
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 620..625
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 641..643
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 643
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 671
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 724..728
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 227
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 322
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 454
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 492
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 685
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 726..774
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT CONFLICT 604
FT /note="T -> S (in Ref. 1; AAC47510)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 814 AA; 94197 MW; 38FA58C5EB17DB16 CRC64;
MAIKLNGSSR SFVPSLRVSA FLIFIFFVIT YIIIYNVSFS EPSWITQDAL KQNIENLDDY
DASCSGYSIG RILREQKRIL ASVRLELTES QVKIEEIRTV QEELQRLIPQ KQLELSALEG
EIEAAQRQLE ELRETQNVKV FLPFSPLQIP RELEQPSQIS PNQLDDIIDY SRCSISSFMP
VYVDIITSGQ SEKEWLNVFQ EVIPNLVETP DKACIKIHIS NGIASPNTTF NSILFNVGSP
IINFQSKSIH VQASKIRSFD FPVDVNHIAV EKVDLTPLLP FQRENLISLI VDNTELNFSA
FSSLSAEPSR RPIVIVKCSQ ENCSLERRRQ LIGSSTFCFL LPSEMFFQDF LSSLQLGCIP
IILSNSQLLP FQDLIDWRRA TYRLPLARLP EAHFIVQSFE ISDIIEMRRV GRLFYETYLA
DRHLLARSLL AALRYKLQIP TREVRRNQAI PLFNSSFTAP KGSVVNVQAN FDDEYLLGPL
ESRVESTSYA YNFTEFQLYS YDFWNIIMSP HYTKEFLVNA AELPTEAEFF EDTKIGFRPI
EPGSGAEFSK ALGGNRQREQ FTVVLLTYER DAVLTGALER LHQLPYLNKI IVVWNNVNRD
PPDTWPSLHI PVEFIRVAEN NLNNRFVPWD RIETEAVLSL DDDIDLMQQE IILAFRVWRE
NRDRIVGFPA RHHARYGDSM FYNSNHTCQM SMILTGAAFI HKNYLTAYTY EMPAEIREHV
NSIKNCEDIA MNYLVSHLTR KPPIKTTSRW TLKCPTCTES LYKEGTHFEK RHECMRLFTK
IYGYNPLKFS QFRADSILFK TRLPQNHQKC FKYV
