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   24-JAN-2024, entry version 166.
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   GlyCosmos; Q9WVK5; 8 sites, No reported glycans.
DR   GlyGen; Q9WVK5; 8 sites.
DR   PhosphoSitePlus; Q9WVK5; -.
DR   PaxDb; 10090-ENSMUSP00000066515; -.
DR   ProteomicsDB; 273591; -.
DR   Antibodypedia; 41869; 144 antibodies from 27 providers.
DR   DNASU; 56386; -.
DR   Ensembl; ENSMUST00000070080.6; ENSMUSP00000066515.6; ENSMUSG00000056124.6.
DR   GeneID; 56386; -.
DR   KEGG; mmu:56386; -.
DR   UCSC; uc008eeu.2; mouse.
DR   AGR; MGI:1928380; -.
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; VVWDCII; -.
DR   OrthoDB; 306273at2759; -.
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 79 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 269 other cell types or tissues.
DR   ExpressionAtlas; Q9WVK5; baseline and differential.
DR   GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR   GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
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   CDD; cd00899; b4GalT; 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; BETA-1,4-GALACTOSYLTRANSFERASE; 1.
DR   PANTHER; PTHR19300:SF47; BETA-1,4-GALACTOSYLTRANSFERASE 6; 1.
DR   Pfam; PF02709; Glyco_transf_7C; 1.
DR   Pfam; PF13733; Glyco_transf_7N; 1.
DR   PRINTS; PR02050; B14GALTRFASE.
DR   SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1.
DR   Genevisible; Q9WVK5; MM.
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
//