B4GA1_HUMAN
ID B4GA1_HUMAN Reviewed; 415 AA.
AC O43505; Q4TTN0;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Beta-1,4-glucuronyltransferase 1 {ECO:0000303|PubMed:25279697, ECO:0000303|PubMed:25279699, ECO:0000312|HGNC:HGNC:15685};
DE EC=2.4.1.- {ECO:0000269|PubMed:19587235, ECO:0000269|PubMed:23359570, ECO:0000269|PubMed:25279697, ECO:0000269|PubMed:25279699};
DE AltName: Full=I-beta-1,3-N-acetylglucosaminyltransferase;
DE Short=iGnT;
DE AltName: Full=N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase;
DE AltName: Full=Poly-N-acetyllactosamine extension enzyme;
DE AltName: Full=UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 1;
GN Name=B4GAT1 {ECO:0000303|PubMed:25279697, ECO:0000303|PubMed:25279699,
GN ECO:0000312|HGNC:HGNC:15685};
GN Synonyms=B3GNT1 {ECO:0000312|HGNC:HGNC:15685}, B3GNT6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND CAUTION.
RX PubMed=9405606; DOI=10.1073/pnas.94.26.14294;
RA Sasaki K., Kurata-Miura K., Ujita M., Angata K., Nakagawa S., Sekine S.,
RA Nishi T., Fukuda M.;
RT "Expression cloning of cDNA encoding a human beta-1,3-N-
RT acetylglucosaminyltransferase that is essential for poly-N-
RT acetyllactosamine synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:14294-14299(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-253.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH LARGE1 AND LARGE2, AND
RP CATALYTIC ACTIVITY.
RX PubMed=19587235; DOI=10.1073/pnas.0904515106;
RA Bao X., Kobayashi M., Hatakeyama S., Angata K., Gullberg D., Nakayama J.,
RA Fukuda M.N., Fukuda M.;
RT "Tumor suppressor function of laminin-binding alpha-dystroglycan requires a
RT distinct beta3-N-acetylglucosaminyltransferase.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:12109-12114(2009).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, VARIANTS MDDGA13 ASP-390 AND VAL-406,
RP CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANTS MDDGA13 ASP-390 AND
RP VAL-406.
RX PubMed=23359570; DOI=10.1093/hmg/ddt021;
RA Buysse K., Riemersma M., Powell G., van Reeuwijk J., Chitayat D.,
RA Roscioli T., Kamsteeg E.J., van den Elzen C., van Beusekom E., Blaser S.,
RA Babul-Hirji R., Halliday W., Wright G.J., Stemple D.L., Lin Y.Y.,
RA Lefeber D.J., van Bokhoven H.;
RT "Missense mutations in beta-1,3-N-acetylglucosaminyltransferase 1 (B3GNT1)
RT cause Walker-Warburg syndrome.";
RL Hum. Mol. Genet. 22:1746-1754(2013).
RN [6]
RP INVOLVEMENT IN MDDGA13.
RX PubMed=23877401; DOI=10.1007/s10048-013-0367-8;
RA Shaheen R., Faqeih E., Ansari S., Alkuraya F.S.;
RT "A truncating mutation in B3GNT1 causes severe Walker-Warburg syndrome.";
RL Neurogenetics 14:243-245(2013).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PATHWAY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF MET-155 AND
RP 227-ASP--ASP-229.
RX PubMed=25279699; DOI=10.7554/elife.03941;
RA Willer T., Inamori K.I., Venzke D., Harvey C., Morgensen G., Hara Y.,
RA Beltran Valero de Bernabe D., Yu L., Wright K.M., Campbell K.P.;
RT "The glucuronyltransferase B4GAT1 is required for initiation of LARGE-
RT mediated alpha-dystroglycan functional glycosylation.";
RL Elife 3:0-0(2014).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=25279697; DOI=10.7554/elife.03943;
RA Praissman J.L., Live D.H., Wang S., Ramiah A., Chinoy Z.S., Boons G.J.,
RA Moremen K.W., Wells L.;
RT "B4GAT1 is the priming enzyme for the LARGE-dependent functional
RT glycosylation of alpha-dystroglycan.";
RL Elife 3:0-0(2014).
CC -!- FUNCTION: Beta-1,4-glucuronyltransferase involved in O-mannosylation of
CC alpha-dystroglycan (DAG1) (PubMed:19587235, PubMed:23359570,
CC PubMed:25279699, PubMed:25279697). Transfers a glucuronic acid (GlcA)
CC residue onto a xylose (Xyl) acceptor to produce the glucuronyl-beta-
CC 1,4-xylose-beta disaccharide primer, which is further elongated by
CC LARGE1, during synthesis of phosphorylated O-mannosyl glycan
CC (PubMed:25279699, PubMed:25279697). Phosphorylated O-mannosyl glycan is
CC a carbohydrate structure present in alpha-dystroglycan (DAG1), which is
CC required for binding laminin G-like domain-containing extracellular
CC proteins with high affinity (PubMed:25279699, PubMed:25279697).
CC Required for axon guidance; via its function in O-mannosylation of
CC alpha-dystroglycan (DAG1) (By similarity).
CC {ECO:0000250|UniProtKB:Q8BWP8, ECO:0000269|PubMed:19587235,
CC ECO:0000269|PubMed:23359570, ECO:0000269|PubMed:25279697,
CC ECO:0000269|PubMed:25279699}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-[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)]-Thr-[protein] + UDP-
CC alpha-D-glucuronate = 3-O-[beta-D-GlcA-(1->3)-beta-D-Xyl-(1->4)-Rib-
CC ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-
CC alpha-D-Man)]-Thr-[protein] + H(+) + UDP; Xref=Rhea:RHEA:46860,
CC Rhea:RHEA-COMP:15023, Rhea:RHEA-COMP:17482, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:142405,
CC ChEBI:CHEBI:177336; Evidence={ECO:0000269|PubMed:19587235,
CC ECO:0000269|PubMed:23359570, ECO:0000269|PubMed:25279697,
CC ECO:0000269|PubMed:25279699};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:25279699};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.0. {ECO:0000269|PubMed:25279699};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000269|PubMed:25279697, ECO:0000269|PubMed:25279699,
CC ECO:0000269|PubMed:9405606}.
CC -!- SUBUNIT: Interacts with LARGE1 and LARGE2.
CC {ECO:0000269|PubMed:19587235}.
CC -!- INTERACTION:
CC O43505; O95461-1: LARGE1; NbExp=2; IntAct=EBI-6138697, EBI-15792998;
CC O43505; Q8N3Y3: LARGE2; NbExp=3; IntAct=EBI-6138697, EBI-2839174;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:19587235, ECO:0000269|PubMed:23359570,
CC ECO:0000269|PubMed:25279699}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:23359570}. Note=Localizes near the trans-Golgi
CC apparatus. {ECO:0000269|PubMed:25279699}.
CC -!- TISSUE SPECIFICITY: In the adult, highly expressed in heart, brain,
CC skeletal muscle and kidney and to a lesser extent in placenta,
CC pancreas, spleen, prostate, testis, ovary, small intestine and colon.
CC Very weak expression in lung, liver, thymus and peripheral blood
CC leukocytes. In fetal highly expressed in brain and kidney and to a
CC lesser extent in lung and liver. {ECO:0000269|PubMed:9405606}.
CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain
CC and eye anomalies A13 (MDDGA13) [MIM:615287]: An autosomal recessive
CC disorder characterized by congenital muscular dystrophy associated with
CC cobblestone lissencephaly and other brain anomalies, eye malformations,
CC profound intellectual disability, and death usually in the first years
CC of life. Included diseases are the more severe Walker-Warburg syndrome
CC and the slightly less severe muscle-eye-brain disease.
CC {ECO:0000269|PubMed:23359570, ECO:0000269|PubMed:23877401}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 49 family.
CC {ECO:0000305}.
CC -!- CAUTION: Was initially characterized as a beta-1,3-N-
CC acetylglucosaminyltransferase involved in the synthesis of poly-N-
CC acetyllactosamine, able to initiate the synthesis or the elongation of
CC the linear poly-N-acetyllactosaminoglycans (PubMed:9405606). However,
CC it was later shown that it acts as a beta-1,4-glucuronyltransferase
CC (PubMed:25279699, PubMed:25279697). {ECO:0000269|PubMed:25279697,
CC ECO:0000269|PubMed:25279699, ECO:0000305|PubMed:9405606}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/b3gnt6/";
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=N-
CC acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_547";
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DR EMBL; AF029893; AAC39538.1; -; mRNA.
DR EMBL; DQ066422; AAY46155.1; -; Genomic_DNA.
DR EMBL; BC021965; AAH21965.1; -; mRNA.
DR CCDS; CCDS8136.1; -.
DR RefSeq; NP_006867.1; NM_006876.2.
DR AlphaFoldDB; O43505; -.
DR BioGRID; 116229; 116.
DR DIP; DIP-48921N; -.
DR IntAct; O43505; 52.
DR MINT; O43505; -.
DR STRING; 9606.ENSP00000309096; -.
DR CAZy; GT49; Glycosyltransferase Family 49.
DR GlyConnect; 1033; 1 N-Linked glycan (1 site).
DR GlyGen; O43505; 2 sites, 1 N-linked glycan (1 site).
DR iPTMnet; O43505; -.
DR PhosphoSitePlus; O43505; -.
DR SwissPalm; O43505; -.
DR BioMuta; B4GAT1; -.
DR EPD; O43505; -.
DR jPOST; O43505; -.
DR MassIVE; O43505; -.
DR MaxQB; O43505; -.
DR PaxDb; O43505; -.
DR PeptideAtlas; O43505; -.
DR PRIDE; O43505; -.
DR ProteomicsDB; 48998; -.
DR Antibodypedia; 2208; 133 antibodies from 22 providers.
DR DNASU; 11041; -.
DR Ensembl; ENST00000311181.5; ENSP00000309096.4; ENSG00000174684.7.
DR GeneID; 11041; -.
DR KEGG; hsa:11041; -.
DR MANE-Select; ENST00000311181.5; ENSP00000309096.4; NM_006876.3; NP_006867.1.
DR UCSC; uc001ohr.4; human.
DR CTD; 11041; -.
DR DisGeNET; 11041; -.
DR GeneCards; B4GAT1; -.
DR HGNC; HGNC:15685; B4GAT1.
DR HPA; ENSG00000174684; Tissue enhanced (brain).
DR MalaCards; B4GAT1; -.
DR MIM; 605517; gene.
DR MIM; 615287; phenotype.
DR neXtProt; NX_O43505; -.
DR OpenTargets; ENSG00000174684; -.
DR Orphanet; 899; Walker-Warburg syndrome.
DR PharmGKB; PA164741279; -.
DR VEuPathDB; HostDB:ENSG00000174684; -.
DR eggNOG; KOG3765; Eukaryota.
DR GeneTree; ENSGT00940000157679; -.
DR HOGENOM; CLU_019238_5_0_1; -.
DR InParanoid; O43505; -.
DR OMA; HQQFLAM; -.
DR OrthoDB; 729091at2759; -.
DR PhylomeDB; O43505; -.
DR TreeFam; TF319168; -.
DR BioCyc; MetaCyc:HS10821-MON; -.
DR BRENDA; 2.4.1.149; 2681.
DR PathwayCommons; O43505; -.
DR Reactome; R-HSA-2022854; Keratan sulfate biosynthesis.
DR Reactome; R-HSA-5083627; Defective LARGE causes MDDGA6 and MDDGB6.
DR Reactome; R-HSA-5173105; O-linked glycosylation.
DR SignaLink; O43505; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 11041; 7 hits in 1066 CRISPR screens.
DR ChiTaRS; B4GAT1; human.
DR GeneWiki; B3GNT1; -.
DR GenomeRNAi; 11041; -.
DR Pharos; O43505; Tbio.
DR PRO; PR:O43505; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O43505; protein.
DR Bgee; ENSG00000174684; Expressed in endothelial cell and 205 other tissues.
DR ExpressionAtlas; O43505; baseline and differential.
DR Genevisible; O43505; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0030173; C:integral component of Golgi membrane; NAS:UniProtKB.
DR GO; GO:0015020; F:glucuronosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008532; F:N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase activity; TAS:Reactome.
DR GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR GO; GO:0018146; P:keratan sulfate biosynthetic process; TAS:Reactome.
DR GO; GO:0035269; P:protein O-linked mannosylation; IDA:UniProtKB.
DR InterPro; IPR043189; B4GAT1.
DR PANTHER; PTHR46420; PTHR46420; 1.
PE 1: Evidence at protein level;
KW Congenital muscular dystrophy; Disease variant; Dystroglycanopathy;
KW Glycoprotein; Glycosyltransferase; Golgi apparatus; Lissencephaly;
KW Manganese; Membrane; Metal-binding; Reference proteome; Signal-anchor;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..415
FT /note="Beta-1,4-glucuronyltransferase 1"
FT /id="PRO_0000080555"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 9..36
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 37..415
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT BINDING 227
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000305|PubMed:25279699"
FT BINDING 229
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000305|PubMed:25279699"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 253
FT /note="T -> S (in dbSNP:rs35429253)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_025019"
FT VARIANT 390
FT /note="N -> D (in MDDGA13; no effect on Golgi localization;
FT loss of beta-1,4-glucuronyltransferase activity;
FT dbSNP:rs397509397)"
FT /evidence="ECO:0000269|PubMed:23359570"
FT /id="VAR_069989"
FT VARIANT 406
FT /note="A -> V (in MDDGA13; no effect on Golgi localization;
FT loss of beta-1,4-glucuronyltransferase activity;
FT dbSNP:rs397509396)"
FT /evidence="ECO:0000269|PubMed:23359570"
FT /id="VAR_069990"
FT MUTAGEN 155
FT /note="M->T: In Mut3; mislocalization to the endoplasmic
FT reticulum."
FT /evidence="ECO:0000269|PubMed:25279699"
FT MUTAGEN 227..229
FT /note="DVD->NVN: In Mut2; mislocalization to the
FT endoplasmic reticulum."
FT /evidence="ECO:0000269|PubMed:25279699"
SQ SEQUENCE 415 AA; 47119 MW; 432D00980EFE2B35 CRC64;
MQMSYAIRCA FYQLLLAALM LVAMLQLLYL SLLSGLHGQE EQDQYFEFFP PSPRSVDQVK
AQLRTALASG GVLDASGDYR VYRGLLKTTM DPNDVILATH ASVDNLLHLS GLLERWEGPL
SVSVFAATKE EAQLATVLAY ALSSHCPDMR ARVAMHLVCP SRYEAAVPDP REPGEFALLR
SCQEVFDKLA RVAQPGINYA LGTNVSYPNN LLRNLAREGA NYALVIDVDM VPSEGLWRGL
REMLDQSNQW GGTALVVPAF EIRRARRMPM NKNELVQLYQ VGEVRPFYYG LCTPCQAPTN
YSRWVNLPEE SLLRPAYVVP WQDPWEPFYV AGGKVPTFDE RFRQYGFNRI SQACELHVAG
FDFEVLNEGF LVHKGFKEAL KFHPQKEAEN QHNKILYRQF KQELKAKYPN SPRRC
