LARG2_RAT
ID LARG2_RAT Reviewed; 690 AA.
AC Q6P7A1;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Xylosyl- and glucuronyltransferase LARGE2 {ECO:0000305};
DE EC=2.4.-.- {ECO:0000250|UniProtKB:Q5XPT3};
DE AltName: Full=Glycosyltransferase-like 1B;
DE AltName: Full=LARGE xylosyl- and glucuronyltransferase 2 {ECO:0000312|RGD:735214};
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:0000312|RGD:735214}; Synonyms=Gyltl1b;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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 -!- SUBUNIT: Interacts with B4GAT1. {ECO:0000250|UniProtKB:Q8N3Y3}.
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; BC061762; AAH61762.1; -; mRNA.
DR RefSeq; NP_954538.1; NM_199107.1.
DR AlphaFoldDB; Q6P7A1; -.
DR SMR; Q6P7A1; -.
DR STRING; 10116.ENSRNOP00000041797; -.
DR CAZy; GT49; Glycosyltransferase Family 49.
DR CAZy; GT8; Glycosyltransferase Family 8.
DR GlyGen; Q6P7A1; 3 sites.
DR PaxDb; Q6P7A1; -.
DR PRIDE; Q6P7A1; -.
DR GeneID; 311202; -.
DR KEGG; rno:311202; -.
DR UCSC; RGD:735214; rat.
DR CTD; 120071; -.
DR RGD; 735214; Large2.
DR VEuPathDB; HostDB:ENSRNOG00000006353; -.
DR eggNOG; KOG3765; Eukaryota.
DR HOGENOM; CLU_019238_3_2_1; -.
DR InParanoid; Q6P7A1; -.
DR OMA; RTACPKQ; -.
DR OrthoDB; 729091at2759; -.
DR PhylomeDB; Q6P7A1; -.
DR TreeFam; TF319168; -.
DR Reactome; R-RNO-5173105; O-linked glycosylation.
DR UniPathway; UPA00378; -.
DR PRO; PR:Q6P7A1; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000006353; Expressed in pancreas and 15 other tissues.
DR Genevisible; Q6P7A1; RN.
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:0043231; C:intracellular membrane-bounded organelle; ISO:RGD.
DR GO; GO:0002162; F:dystroglycan binding; ISO:RGD.
DR GO; GO:0015020; F:glucuronosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0016757; F:glycosyltransferase activity; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042285; F:xylosyltransferase activity; ISS:UniProtKB.
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..690
FT /note="Xylosyl- and glucuronyltransferase LARGE2"
FT /id="PRO_0000226813"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..28
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..690
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 67..342
FT /note="Xylosyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT REGION 343..686
FT /note="Glucuronyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:O95461"
FT BINDING 171
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8N3Y3"
FT BINDING 173
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8N3Y3"
FT BINDING 491
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8N3Y3"
FT BINDING 493
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8N3Y3"
FT CARBOHYD 50
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 201
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 690 AA; 79309 MW; 79C609E33EDD33E3 CRC64;
MLPRGRPRAL GAALLLLLLL VVGFFLFGRD PEYGLGTTAT LDGDPYGSRN RSTSSLQLLL
PPKCEMLHVA IVCAGYNSSR EIITLMKSVL FYRKNPLHLH LITDAVARNI LETLFRTWMV
PAVVVSFYDA EELKPLVSWI PNKHYSGLYG LMKLVLPSVL PLSLARVIVL DTDVTFSSDI
MELWALFGHF SDKQVVGLVE NQSDWYLGNL WKNHRPWPAL GRGFNTGVIL LWLDRLQQIG
WEQMWKLTAK RELLTLTATS LADQDIFNAV IKEHPELVHP LPCVWNVQLS DHTLAERCYL
EAADLKVIHW NSPKKLRVKN KHAEFFRDLH LTFLGFDGKL LCRELFGCPN QFPPGVEQLQ
QALAQLDEEE PCFEFRQQQL TVHRVHITFL SHQPPPPRPH DVTLVAQLSM DRLQMLEALC
RHWRGPMSLA LYLTDAEAQQ FLRFVETSPV LSARKDVAYH VVYRDGPLYP VNQLRNVALA
QALTPYVFLS DIDFLPAYSL YDYLRASIEQ LALGRRQRKA ALVVPAFETL HYRFSFPNSK
AELLTLLDAG SLHTFRYHEW PQGHASTDYT RWREAQAPYR VQWSADYEPY VVVPRDCPRY
DPRFVGFGWN KVAHIIELDA QEYEFLVLPE AFSIHLPHAP SLDISRFRSS PTYRDCLQAL
KEEFHQDLSR RYGSAALKYL TALQQSRSRA
