B4GT6_MOUSE
ID B4GT6_MOUSE Reviewed; 382 AA.
AC Q9WVK5;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Beta-1,4-galactosyltransferase 6 {ECO:0000305};
DE Short=Beta-1,4-GalTase 6;
DE Short=Beta4Gal-T6;
DE Short=b4Gal-T6;
DE EC=2.4.1.-;
DE AltName: Full=Glucosylceramide beta-1,4-galactosyltransferase;
DE EC=2.4.1.274 {ECO:0000269|PubMed:30114188};
DE AltName: Full=Lactosylceramide synthase {ECO:0000303|PubMed:23882130, ECO:0000303|PubMed:30114188};
DE Short=LacCer synthase {ECO:0000303|PubMed:23882130, ECO:0000303|PubMed:30114188};
DE AltName: Full=UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 6;
DE AltName: Full=UDP-Gal:glucosylceramide beta-1,4-galactosyltransferase {ECO:0000250|UniProtKB:Q9UBX8};
DE AltName: Full=UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 6;
GN Name=B4galt6 {ECO:0000312|MGI:MGI:1928380};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Takizawa M., Nomura T., Wakisaka E., Aoki J., Arai H., Inoue K., Matsuo N.;
RT "cDNA cloning and expression of mouse lactosylceramide synthase.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Lo N.-W., Shaper N.L., Shaper J.H.;
RT "Murine beta-1,4-galactosyltransferase family members.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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 AS GLUCOSYLCERAMIDE BETA-1,4-GALACTOSYLTRANSFERASE, CATALYTIC
RP ACTIVITY, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=23882130; DOI=10.1093/glycob/cwt054;
RA Tokuda N., Numata S., Li X., Nomura T., Takizawa M., Kondo Y.,
RA Yamashita Y., Hashimoto N., Kiyono T., Urano T., Furukawa K., Furukawa K.;
RT "Beta4GalT6 is involved in the synthesis of lactosylceramide with less
RT intensity than beta4GalT5.";
RL Glycobiology 23:1175-1183(2013).
RN [5]
RP FUNCTION AS GLUCOSYLCERAMIDE BETA-1,4-GALACTOSYLTRANSFERASE, CATALYTIC
RP ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=30114188; DOI=10.1371/journal.pgen.1007545;
RA Yoshihara T., Satake H., Nishie T., Okino N., Hatta T., Otani H.,
RA Naruse C., Suzuki H., Sugihara K., Kamimura E., Tokuda N., Furukawa K.,
RA Fururkawa K., Ito M., Asano M.;
RT "Lactosylceramide synthases encoded by B4galt5 and 6 genes are pivotal for
RT neuronal generation and myelin formation in mice.";
RL PLoS Genet. 14:E1007545-E1007545(2018).
CC -!- FUNCTION: Catalyzes the synthesis of lactosylceramide (LacCer) via the
CC transfer of galactose from UDP-galactose to glucosylceramide (GlcCer)
CC (PubMed:23882130, PubMed:30114188). LacCer is the starting point in the
CC biosynthesis of all gangliosides (membrane-bound glycosphingolipids)
CC which play pivotal roles in the CNS including neuronal maturation and
CC axonal and myelin formation (PubMed:30114188).
CC {ECO:0000269|PubMed:23882130, ECO:0000269|PubMed:30114188}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine + UDP-alpha-D-
CC galactose = a beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)-Cer(d18:1(4E)) +
CC H(+) + UDP; Xref=Rhea:RHEA:31495, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17950, ChEBI:CHEBI:22801, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:66914; EC=2.4.1.274;
CC Evidence={ECO:0000269|PubMed:23882130, ECO:0000269|PubMed:30114188};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31496;
CC Evidence={ECO:0000269|PubMed:30114188};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:O88419};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O88419};
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:O88419};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA. {ECO:0000250|UniProtKB:O88419}.
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- PATHWAY: Sphingolipid metabolism.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane
CC {ECO:0000250|UniProtKB:P15291}; Single-pass type II membrane protein.
CC Note=Trans cisternae of Golgi stack. {ECO:0000250|UniProtKB:P15291}.
CC -!- TISSUE SPECIFICITY: Brain and kidney. {ECO:0000269|PubMed:23882130}.
CC -!- DISRUPTION PHENOTYPE: Single knockout mice are born normally and grow
CC to adulthood without apparent abnormalities (PubMed:23882130).
CC Decreased glucosylceramide beta-1,4-galactosyltransferase activity seen
CC in the brain of female mice whereas minimal or no reduction in the
CC enzyme activity seen in the male brain (PubMed:23882130). Double
CC knockout mice of B4GALT5 and B4GALT6 genes develop normally during
CC embryogenesis and perinatal stage (PubMed:30114188). However, they show
CC growth retardation and motor deficits with hindlimb dysfunction at 2
CC weeks of age, and they all die by 4 weeks of age (PubMed:30114188).
CC Axonal and myelin formation are remarkably impaired in the spinal cords
CC and increased immature neurons in the cerebral cortices seen
CC (PubMed:30114188). Glucosylceramide beta-1,4-galactosyltransferase
CC activity and major brain gangliosides are completely absent in the
CC brain (PubMed:30114188). {ECO:0000269|PubMed:23882130,
CC ECO:0000269|PubMed:30114188}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 7 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=b4GalT6;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_mou_465";
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DR EMBL; AF097158; AAD41694.1; -; mRNA.
DR EMBL; AF142674; AAF22224.1; -; mRNA.
DR EMBL; BC011149; AAH11149.1; -; mRNA.
DR CCDS; CCDS29086.1; -.
DR RefSeq; NP_062711.1; NM_019737.2.
DR AlphaFoldDB; Q9WVK5; -.
DR SMR; Q9WVK5; -.
DR STRING; 10090.ENSMUSP00000066515; -.
DR SwissLipids; SLP:000001927; -.
DR CAZy; GT7; Glycosyltransferase Family 7.
DR GlyGen; Q9WVK5; 8 sites.
DR PhosphoSitePlus; Q9WVK5; -.
DR PaxDb; Q9WVK5; -.
DR PRIDE; Q9WVK5; -.
DR ProteomicsDB; 273591; -.
DR Antibodypedia; 41869; 121 antibodies from 27 providers.
DR DNASU; 56386; -.
DR Ensembl; ENSMUST00000070080; ENSMUSP00000066515; ENSMUSG00000056124.
DR GeneID; 56386; -.
DR KEGG; mmu:56386; -.
DR UCSC; uc008eeu.2; mouse.
DR CTD; 9331; -.
DR MGI; MGI:1928380; B4galt6.
DR VEuPathDB; HostDB:ENSMUSG00000056124; -.
DR eggNOG; KOG3916; Eukaryota.
DR GeneTree; ENSGT00940000158138; -.
DR HOGENOM; CLU_044391_6_0_1; -.
DR InParanoid; Q9WVK5; -.
DR OMA; NFTYSPF; -.
DR OrthoDB; 1201618at2759; -.
DR PhylomeDB; Q9WVK5; -.
DR TreeFam; TF312834; -.
DR BRENDA; 2.4.1.274; 3474.
DR Reactome; R-MMU-2022854; Keratan sulfate biosynthesis.
DR Reactome; R-MMU-913709; O-linked glycosylation of mucins.
DR Reactome; R-MMU-975577; N-Glycan antennae elongation.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 56386; 1 hit in 74 CRISPR screens.
DR ChiTaRS; B4galt6; mouse.
DR PRO; PR:Q9WVK5; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q9WVK5; protein.
DR Bgee; ENSMUSG00000056124; Expressed in dorsomedial nucleus of hypothalamus and 267 other tissues.
DR ExpressionAtlas; Q9WVK5; baseline and differential.
DR Genevisible; Q9WVK5; MM.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008378; F:galactosyltransferase activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008489; F:UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity; IMP:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0022010; P:central nervous system myelination; IMP:UniProtKB.
DR GO; GO:0021955; P:central nervous system neuron axonogenesis; IMP:UniProtKB.
DR GO; GO:0010706; P:ganglioside biosynthetic process via lactosylceramide; IMP:UniProtKB.
DR GO; GO:0006688; P:glycosphingolipid biosynthetic process; ISO:MGI.
DR GO; GO:0070085; P:glycosylation; IBA:GO_Central.
DR GO; GO:0001572; P:lactosylceramide biosynthetic process; ISO:MGI.
DR GO; GO:0042551; P:neuron maturation; IMP:UniProtKB.
DR GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:MGI.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR003859; Galactosyl_T.
DR InterPro; IPR027791; Galactosyl_T_C.
DR InterPro; IPR027995; Galactosyl_T_N.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR19300; PTHR19300; 1.
DR Pfam; PF02709; Glyco_transf_7C; 1.
DR Pfam; PF13733; Glyco_transf_7N; 1.
DR PRINTS; PR02050; B14GALTRFASE.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Calcium; Disulfide bond; Glycoprotein; Glycosyltransferase;
KW Golgi apparatus; Lipid biosynthesis; Lipid metabolism; Magnesium;
KW Manganese; Membrane; Metal-binding; Reference proteome; Signal-anchor;
KW Sphingolipid metabolism; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..382
FT /note="Beta-1,4-galactosyltransferase 6"
FT /id="PRO_0000080548"
FT TOPO_DOM 1..15
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 16..35
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 36..382
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT BINDING 163..167
FT /ligand="UDP-alpha-D-galactose"
FT /ligand_id="ChEBI:CHEBI:66914"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 202..204
FT /ligand="UDP-alpha-D-galactose"
FT /ligand_id="ChEBI:CHEBI:66914"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 229..230
FT /ligand="UDP-alpha-D-galactose"
FT /ligand_id="ChEBI:CHEBI:66914"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 230
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 258
FT /ligand="UDP-alpha-D-galactose"
FT /ligand_id="ChEBI:CHEBI:66914"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 290
FT /ligand="UDP-alpha-D-galactose"
FT /ligand_id="ChEBI:CHEBI:66914"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 292..295
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 323..324
FT /ligand="UDP-alpha-D-galactose"
FT /ligand_id="ChEBI:CHEBI:66914"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 323
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 334
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 83
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 99
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 307
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 367
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 108..152
FT /evidence="ECO:0000250|UniProtKB:P15291"
FT DISULFID 223..242
FT /evidence="ECO:0000250|UniProtKB:P15291"
SQ SEQUENCE 382 AA; 44759 MW; 0223621127896358 CRC64;
MSALKRMMRV SNRSLIAFIF FFSLSTSCLY FIYVAPGIAN TYLFMVQARG IMLRENVKTI
GHMIRLYTNK NTTLNGTDYP EGNNTSDYLV QTTTYLPQNF TYLPHLPCPE KLPYMRGFLS
VNVSEISFDE VHQLFSKDSE IGPGGHWRPK DCKPRWKVAV LIPFRNRHEH LPIFFLHLIP
MLQKQRLEFA FYVIEQTGTQ PFNRAMLFNV GFKEAMKDRA WDCVIFHDVD HLPENDRNYY
GCGEMPRHFA AKLDKYMYIL PYKEFFGGVS GLTVEQFRKI NGFPNAFWGW GGEDDDLWNR
VHYAGYNVTR PEGDLGKYIS IPHHHRGEVQ FLGRYKLLRY SKERQYIDGL NNLLYTPKIL
VDRLYTNISV NLMPELAPIE DY
