LARG1_DANRE
ID LARG1_DANRE Reviewed; 757 AA.
AC Q66PG2;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Xylosyl- and glucuronyltransferase LARGE1 {ECO:0000305};
DE EC=2.4.-.- {ECO:0000250|UniProtKB:O95461};
DE AltName: Full=Acetylglucosaminyltransferase-like 1A;
DE AltName: Full=Glycosyltransferase-like protein;
DE AltName: Full=LARGE xylosyl- and glucuronyltransferase 1 {ECO:0000250|UniProtKB:O95461};
DE Includes:
DE RecName: Full=Alpha-1,3-xylosyltransferase LARGE1 {ECO:0000305};
DE EC=2.4.2.- {ECO:0000250|UniProtKB:O95461};
DE Includes:
DE RecName: Full=Beta-1,3-glucuronyltransferase LARGE1 {ECO:0000305};
DE EC=2.4.1.- {ECO:0000250|UniProtKB:O95461};
GN Name=large1 {ECO:0000250|UniProtKB:O95461}; Synonyms=large;
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).
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. Elongates the
CC glucuronyl-beta-1,4-xylose-beta disaccharide primer structure initiated
CC by B4GAT1 by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-]
CC to produce a heteropolysaccharide. Requires the phosphorylation of core
CC M3 (O-mannosyl trisaccharide) by POMK to elongate the glucuronyl-beta-
CC 1,4-xylose-beta disaccharide primer (By similarity). Plays a key role
CC in skeletal muscle function and regeneration (By similarity).
CC {ECO:0000250|UniProtKB:O95461, ECO:0000250|UniProtKB:Q9Z1M7}.
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:O95461};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57337;
CC Evidence={ECO:0000250|UniProtKB:O95461};
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:O95461};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67925;
CC Evidence={ECO:0000250|UniProtKB:O95461};
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:O95461};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68369;
CC Evidence={ECO:0000250|UniProtKB:O95461};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:O95461};
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:O95461};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000250|UniProtKB:O95461}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:O95461}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:O95461}.
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; AY662338; AAU12251.1; -; mRNA.
DR RefSeq; NP_001004537.1; NM_001004537.1.
DR AlphaFoldDB; Q66PG2; -.
DR SMR; Q66PG2; -.
DR STRING; 7955.ENSDARP00000013130; -.
DR CAZy; GT49; Glycosyltransferase Family 49.
DR CAZy; GT8; Glycosyltransferase Family 8.
DR PaxDb; Q66PG2; -.
DR PRIDE; Q66PG2; -.
DR GeneID; 446213; -.
DR KEGG; dre:446213; -.
DR CTD; 9215; -.
DR ZFIN; ZDB-GENE-061204-1; large1.
DR eggNOG; KOG3765; Eukaryota.
DR InParanoid; Q66PG2; -.
DR OrthoDB; 729091at2759; -.
DR PhylomeDB; Q66PG2; -.
DR Reactome; R-DRE-5173105; O-linked glycosylation.
DR UniPathway; UPA00378; -.
DR PRO; PR:Q66PG2; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
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:0016758; F:hexosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
DR GO; GO:0042285; F:xylosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0006486; P:protein glycosylation; ISS:UniProtKB.
DR GO; GO:0035269; P:protein O-linked mannosylation; ISS:UniProtKB.
DR GO; GO:0060538; P:skeletal muscle organ development; ISS:UniProtKB.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; 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 Coiled coil; Glycoprotein; Glycosyltransferase; Golgi apparatus; Manganese;
KW Membrane; Metal-binding; Multifunctional enzyme; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..757
FT /note="Xylosyl- and glucuronyltransferase LARGE1"
FT /id="PRO_0000226810"
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..757
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 76..127
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 139..414
FT /note="Xylosyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT REGION 415..757
FT /note="Glucuronyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT COILED 50..82
FT /evidence="ECO:0000255"
FT COMPBIAS 85..100
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 243
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT BINDING 245
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT BINDING 564
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT BINDING 566
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 273
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 738
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 757 AA; 87673 MW; 88AB8E3E59172775 CRC64;
MLGMCRGRRK FVAASLALIF IPALTWLYLS SANITVKPLP LSPLDPQSSA VVGAAAEHQS
LELRLRDVEE HNNALRREIS RTPRVPTHSS HPSSSRHGNQ LHTHSTEEGT GDSEAKKGAA
AGNSSDCVPQ PVVKKCETIH IAIVCAGYNA SRDVVTLVKS VLFHRRNPLH FHIITDSIAR
KILADLFHTW MVPAVHVNFY DADELKSEVS WIPNKHYSGI HGLMKLVLTK TLPSDLEKVI
VLDTDITFAT DIAELWVVFH KFKGQQVLGL VENQSDWYLG NLWKNHRPWP ALGRGFNTGV
ILLLLDRLRK LKWEQMWRLT AERELMSMLS TSLADQDIFN AVIKQNPFLV HQLPCYWNVQ
LSDHTRSEKC YKDVSDLKVI HWNSPKKLRV KNKHVEFFRN LYLTFLEYDG NLLRRELFGC
PSETDHNSEN LQKTLSELDE DDPCYEFRRE RFTVHRTHVY FLHYEYEPTV DNTDVTLVAQ
LSMDRLQMLE AICKHWEGPI SLALYLSDAE AQQFLRYAQG SEVLMSRSNV GYHIVYKEGQ
FYPVNLLRNV AMGQVNTPYM FLSDIDFLPM YGLYEYLRKS VVQLDMGNTK KALVVPAFET
LRYRLSFPKS KAELLSQLDM GTLFTFRYHV WTKGHAPTDF AKWRTATTPY RVQWEADFEP
YVMVRRESPE YDRRFVGFGW NKVAHIMELD AQEYEFVVLP NAYMIHMPHA PSFDITKFRS
NKQYRACLKT LKEEFQQNMS RRYGFAALKY MTVDNNS
