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   27-MAR-2024, entry version 154.
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}.
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; 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.K01G5.6.2; -.
DR   CAZy; GT47; Glycosyltransferase Family 47.
DR   CAZy; GT64; Glycosyltransferase Family 64.
DR   GlyCosmos; O01705; 7 sites, No reported glycans.
DR   EPD; O01705; -.
DR   PaxDb; 6239-K01G5-6; -.
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   AGR; WB:WBGene00004361; -.
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; 1220028at2759; -.
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 cell types or 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: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   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; 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         570
FT                   /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:57705"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT   BINDING         595
FT                   /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:57705"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT   BINDING         620
FT                   /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:57705"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT   BINDING         625
FT                   /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:57705"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT   BINDING         641
FT                   /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:57705"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT   BINDING         642
FT                   /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:57705"
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         643
FT                   /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:57705"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT   BINDING         727
FT                   /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:57705"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT   BINDING         728
FT                   /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:57705"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT   BINDING         771
FT                   /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:57705"
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
//