LARG1_CHICK
ID LARG1_CHICK Reviewed; 756 AA.
AC Q66PG3;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 82.
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 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 Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
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; AY662337; AAU12250.1; -; mRNA.
DR RefSeq; NP_001004383.1; NM_001004383.1.
DR AlphaFoldDB; Q66PG3; -.
DR STRING; 9031.ENSGALP00000020480; -.
DR CAZy; GT49; Glycosyltransferase Family 49.
DR CAZy; GT8; Glycosyltransferase Family 8.
DR PaxDb; Q66PG3; -.
DR GeneID; 418062; -.
DR KEGG; gga:418062; -.
DR CTD; 9215; -.
DR VEuPathDB; HostDB:geneid_418062; -.
DR eggNOG; KOG3765; Eukaryota.
DR InParanoid; Q66PG3; -.
DR OrthoDB; 729091at2759; -.
DR PhylomeDB; Q66PG3; -.
DR UniPathway; UPA00378; -.
DR PRO; PR:Q66PG3; -.
DR Proteomes; UP000000539; 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..756
FT /note="Xylosyl- and glucuronyltransferase LARGE1"
FT /id="PRO_0000226809"
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..756
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 42..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 138..413
FT /note="Xylosyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT REGION 414..756
FT /note="Glucuronyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT COILED 55..90
FT /evidence="ECO:0000255"
FT BINDING 242
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT BINDING 244
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT BINDING 563
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT BINDING 565
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 756 AA; 88046 MW; BC9DC75B9349C92E CRC64;
MLGICRGRRK FLAASLTVLF VPAVTWIYLF AGSFEDGKPV SLSPLESQPH SPRYTASSQR
DRESLEVRMR EVEEENRVLR KQLSLAQGRS PSHHRGNHSK TYSMEEGTGD SESLRAGIVA
GNSSECGQQP AVEKCETIHV AIVCAGYNAS RDVVTLVKSV LFHRRNPLHF HLIADAIAKQ
ILATLFQTWM VPAVRIDFYD ADELKSEVSW IPNKHYSGIY GLMKLVLTKT LPSNLERVIV
LDTDITFATD IAELWAVFHK FKGQQVLGLV ENQSDWYLGN LWKNHRPWPA LGRGYNTGVI
LLLLDKLRKM KWEQMWRLTA ERELMSMLST SLADQDIFNA VIKQNPFLVY QLPCFWNVQL
SDHTRSEQCY RDVSDLKVIH WNSPKKLRVK NKHVEFFRNL YLTFLEYDGN LLRRELFGCP
SEADVNSENL QKQLSEPDED DLCYEFRRER FTVHRTHLYF LHYEYEPASD NTDVTLVAQL
SMDRLQMLEA ICKHWEDPIS LALYLSDAEA QQFLRYAQGS EVLMSRHNVG YHIVYKEGQF
YPVNLLRNVA MKHISTPYMF LSDIDFLPMY GLYEYLRKSV TQLDLANTKK ALIIPAFETL
RYRLSFPKSK AELLSMLDMG TLFTFRYHVW TKGHAPTNFA KWRTATTPYR VEWEADFEPY
VVVRKDCPEY DRRFVGFGWN KVAHIMELDA QEYEFTVLPN AYMIHMPHAP SFDITKFRSN
KQYRICLKTL KEEFQQDMSR HYGFAALKYL TAENNS
