LARG2_DANRE
ID LARG2_DANRE Reviewed; 750 AA.
AC Q66PG1; Q1LUJ7; Q1LV71;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Xylosyl- and glucuronyltransferase LARGE2s {ECO:0000250|UniProtKB:Q8N3Y3};
DE EC=2.4.-.- {ECO:0000250|UniProtKB:Q5XPT3};
DE AltName: Full=Glycosyltransferase-like 1B;
DE AltName: Full=LARGE xylosyl- and glucuronyltransferase 2 {ECO:0000250|UniProtKB:Q8N3Y3};
DE Includes:
DE RecName: Full=Alpha-1,3-xylosyltransferase LARGE2 {ECO:0000305};
DE EC=2.4.2.- {ECO:0000250|UniProtKB:Q5XPT3};
DE Includes:
DE RecName: Full=Beta-1,3-glucuronyltransferase LARGE2 {ECO:0000305};
DE EC=2.4.1.- {ECO:0000250|UniProtKB:Q5XPT3};
GN Name=large2 {ECO:0000250|UniProtKB:Q8N3Y3}; Synonyms=gyltl1b;
GN ORFNames=si:ch211-206g24.1, si:ch211-282n12.1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15958417; DOI=10.1093/glycob/cwi094;
RA Grewal P.K., McLaughlan J.M., Moore C.J., Browning C.A., Hewitt J.E.;
RT "Characterization of the LARGE family of putative glycosyltransferases
RT associated with dystroglycanopathies.";
RL Glycobiology 15:912-923(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
CC -!- FUNCTION: Bifunctional glycosyltransferase with both alpha-1,3-
CC xylosyltransferase and beta-1,3-glucuronyltransferase activities
CC involved in the maturation of alpha-dystroglycan (DAG1) by
CC glycosylation leading to DAG1 binding to laminin G-like domain-
CC containing extracellular proteins with high affinity and in a
CC phosphorylated-O-mannosyl trisaccharide dependent manner. Elongates the
CC glucuronyl-beta-1,4-xylose-beta disaccharide primer structure by adding
CC repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a
CC heteropolysaccharide (By similarity). Supports the maturation of DAG1
CC more effectively than LARGE1 (By similarity). In addition, can modify
CC both heparan sulfate (HS)- and chondroitin/dermatan sulfate (CS/DS)-
CC proteoglycans (PGs), namely GPC4, with a glycosaminoglycan (GAG)-like
CC polysaccharide composed of xylose and glucuronic acid to confer laminin
CC binding (By similarity). {ECO:0000250|UniProtKB:Q5XPT3,
CC ECO:0000250|UniProtKB:Q8N3Y3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-[beta-D-GlcA-(1->3)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-
CC beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr-
CC [protein] + UDP-alpha-D-xylose = 3-O-[alpha-D-Xyl-(1->3)-beta-D-GlcA-
CC (1->4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-
CC beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr-[protein] + H(+) + UDP;
CC Xref=Rhea:RHEA:57336, Rhea:RHEA-COMP:17482, Rhea:RHEA-COMP:17483,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57632, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:177336, ChEBI:CHEBI:177352;
CC Evidence={ECO:0000250|UniProtKB:Q5XPT3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57337;
CC Evidence={ECO:0000250|UniProtKB:Q5XPT3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-{(1->[3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->](n)-4)-beta-
CC D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-
CC (1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + UDP-alpha-D-glucuronate =
CC 3-O-{beta-D-GlcA-(1->[3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->](n)-4)-
CC beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-
CC GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + H(+) + UDP;
CC Xref=Rhea:RHEA:67924, Rhea:RHEA-COMP:17484, Rhea:RHEA-COMP:17486,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:177354, ChEBI:CHEBI:177355;
CC Evidence={ECO:0000250|UniProtKB:Q5XPT3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67925;
CC Evidence={ECO:0000250|UniProtKB:Q5XPT3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-{beta-D-GlcA-(1->[3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-
CC (1->](n)-4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-
CC (1->3)-beta-D-GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + UDP-
CC alpha-D-xylose = 3-O-{(1->[3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-
CC (1->](n+1)-4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-
CC (1->3)-beta-D-GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + H(+)
CC + UDP; Xref=Rhea:RHEA:68368, Rhea:RHEA-COMP:17485, Rhea:RHEA-
CC COMP:17486, ChEBI:CHEBI:15378, ChEBI:CHEBI:57632, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:177354, ChEBI:CHEBI:177355;
CC Evidence={ECO:0000250|UniProtKB:Q5XPT3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68369;
CC Evidence={ECO:0000250|UniProtKB:Q5XPT3};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q5XPT3};
CC Note=Binds 2 Mn(2+) ions per subunit. The xylosyltransferase part binds
CC one Mn(2+) and the beta-1,3-glucuronyltransferase part binds one
CC Mn(2+). {ECO:0000250|UniProtKB:Q5XPT3};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000250|UniProtKB:Q5XPT3}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q5XPT3}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q5XPT3}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the
CC glycosyltransferase 49 family. {ECO:0000305}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the
CC glycosyltransferase 8 family. {ECO:0000305}.
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DR EMBL; AY662339; AAU12252.1; -; mRNA.
DR EMBL; BX908385; CAK04901.1; -; Genomic_DNA.
DR EMBL; BX936304; CAK04442.1; -; Genomic_DNA.
DR RefSeq; NP_001004538.1; NM_001004538.1.
DR RefSeq; XP_017207405.1; XM_017351916.1.
DR AlphaFoldDB; Q66PG1; -.
DR SMR; Q66PG1; -.
DR STRING; 7955.ENSDARP00000019858; -.
DR CAZy; GT49; Glycosyltransferase Family 49.
DR CAZy; GT8; Glycosyltransferase Family 8.
DR PaxDb; Q66PG1; -.
DR Ensembl; ENSDART00000015786; ENSDARP00000019858; ENSDARG00000017058.
DR Ensembl; ENSDART00000127953; ENSDARP00000108343; ENSDARG00000017058.
DR Ensembl; ENSDART00000172328; ENSDARP00000130814; ENSDARG00000017058.
DR GeneID; 446214; -.
DR KEGG; dre:446214; -.
DR CTD; 120071; -.
DR ZFIN; ZDB-GENE-050419-253; large2.
DR eggNOG; KOG3765; Eukaryota.
DR GeneTree; ENSGT00940000158758; -.
DR InParanoid; Q66PG1; -.
DR OMA; RTACPKQ; -.
DR PhylomeDB; Q66PG1; -.
DR TreeFam; TF319168; -.
DR Reactome; R-DRE-5173105; O-linked glycosylation.
DR UniPathway; UPA00378; -.
DR PRO; PR:Q66PG1; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 18.
DR Bgee; ENSDARG00000017058; Expressed in retina and 45 other tissues.
DR ExpressionAtlas; Q66PG1; baseline.
DR GO; GO:0005794; C:Golgi apparatus; ISS:ZFIN.
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:0015020; F:glucuronosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042285; F:xylosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0006486; P:protein glycosylation; ISS:ZFIN.
DR GO; GO:0035269; P:protein O-linked mannosylation; ISS:UniProtKB.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR002495; Glyco_trans_8.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR Pfam; PF01501; Glyco_transf_8; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Glycosyltransferase; Golgi apparatus; Manganese; Membrane;
KW Metal-binding; Multifunctional enzyme; Reference proteome; Signal-anchor;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..750
FT /note="Xylosyl- and glucuronyltransferase LARGE2s"
FT /id="PRO_0000226815"
FT TOPO_DOM 1..10
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 11..31
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 32..750
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 132..407
FT /note="Xylosyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT REGION 408..750
FT /note="Glucuronyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT BINDING 236
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8N3Y3"
FT BINDING 238
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8N3Y3"
FT BINDING 557
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8N3Y3"
FT BINDING 559
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8N3Y3"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 87
FT /note="A -> V (in Ref. 2; CAK04442)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 750 AA; 86987 MW; 79C9BAC9F707CBB2 CRC64;
MLCPCRGKLK LLVVSLSFVI LFTWLYLLVG NSENGRSLLL SACLVESTEA RLLERDVLAS
RVREVEEENR QIRLQLSQSQ GLAGQPAEGN YGNQQWVASA DTGPEDVENT AEERANHSEC
SRSPTAEKCE LLHVACVCAG HNASRDVVTL VKSILFHRRN PLHFHFITDT VANQILSTLF
QSWMVPSVQV SFYDADELKS EVSWIPNKHY SGIYGLMKLT LTKALPSNLS KVIVLDTDIT
FATDIAELWA IFRKFTEKQV IGLVENQSDW YLGNLWKNHK PWPALGRGFN TGVILLYLER
LRRMGWEQMW RLTAERELMS MLSTSLADQD IFNAFIKQNP VLVHQLPCFW NVQLSDHTRS
EQCYTEVSDL KVIHWNSPKK LRVKNKHVEF FRNLYLTFLE YDGNLLRREL FGCPSQASSE
STVLQQALEE LDEDDQCYDF RRERIMLHRV HLYFLQYEYS PTDDGTDITL VAQLSMDRLQ
MLEAICKHWE GPISLALYMS DAEAQQFLRY AQASEVLKNR KNVGYHIVYK EGQFYPVNLV
RNVALRNVNT PYVFLTDVDF LPMYGLYDYL RKSIVQLDMA NTKKALVVPA FETLRYRLSF
PKSKAELLSM LDMGTLYTFR YHVWTKGHAP TNYAKWRTAT TPYKVEWEAD FEPYVVVRRD
CPEYDQRFVG FGWNKVSHIM ELDAQEYDLI VLPNAFMIHM PHAPSFDISK FRSSPSYRYC
LTTLKDEFHQ DLSRKYGSAA LKYLTAQRNI
