ID   B4GT6_HUMAN             Reviewed;         382 AA.
AC   Q9UBX8; O60514; Q6NT09;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   24-JAN-2024, entry version 182.
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:1551920, ECO:0000269|PubMed:3099851};
DE   AltName: Full=Lactosylceramide synthase {ECO:0000303|PubMed:24498430};
DE            Short=LacCer synthase {ECO:0000303|PubMed:24498430};
DE   AltName: Full=UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 6;
DE   AltName: Full=UDP-Gal:glucosylceramide beta-1,4-galactosyltransferase {ECO:0000303|PubMed:3099851};
DE   AltName: Full=UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 6;
GN   Name=B4GALT6 {ECO:0000312|HGNC:HGNC:929};
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] (ISOFORM 1).
RX   PubMed=9597550; DOI=10.1093/glycob/8.5.517;
RA   Lo N.-W., Shaper J.H., Pevsner J., Shaper N.L.;
RT   "The expanding beta 4-galactosyltransferase gene family: messages from the
RT   databanks.";
RL   Glycobiology 8:517-526(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=10320813; DOI=10.1016/s1388-1981(99)00051-7;
RA   Takizawa M., Nomura T., Wakisaka E., Yoshizuka N., Aoki J., Arai H.,
RA   Inoue K., Hattori M., Matsuo N.;
RT   "cDNA cloning and expression of human lactosylceramide synthase.";
RL   Biochim. Biophys. Acta 1438:301-304(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Sato T.;
RT   "Human beta-1,4-galactosyltransferase VI.";
RL   Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16177791; DOI=10.1038/nature03983;
RA   Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA   Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA   Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA   Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA   Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA   Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA   Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA   Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA   Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT   "DNA sequence and analysis of human chromosome 18.";
RL   Nature 437:551-555(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Lung;
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   [7]
RP   FUNCTION AS GLUCOSYLCERAMIDE BETA-1,4-GALACTOSYLTRANSFERASE, CATALYTIC
RP   ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=3099851; DOI=10.1016/0304-4165(87)90136-x;
RA   Chatterjee S., Castiglione E.;
RT   "UDPgalactose:glucosylceramide beta 1->4-galactosyltransferase activity in
RT   human proximal tubular cells from normal and familial hypercholesterolemic
RT   homozygotes.";
RL   Biochim. Biophys. Acta 923:136-142(1987).
RN   [8]
RP   FUNCTION AS GLUCOSYLCERAMIDE BETA-1,4-GALACTOSYLTRANSFERASE, AND CATALYTIC
RP   ACTIVITY.
RX   PubMed=1551920; DOI=10.1016/s0021-9258(19)50550-6;
RA   Chatterjee S., Ghosh N., Khurana S.;
RT   "Purification of uridine diphosphate-galactose:glucosyl ceramide, beta 1-4
RT   galactosyltransferase from human kidney.";
RL   J. Biol. Chem. 267:7148-7153(1992).
RN   [9]
RP   REVIEW.
RX   PubMed=10580128; DOI=10.1016/s0304-4165(99)00168-3;
RA   Amado M., Almeida R., Schwientek T., Clausen H.;
RT   "Identification and characterization of large galactosyltransferase gene
RT   families: galactosyltransferases for all functions.";
RL   Biochim. Biophys. Acta 1473:35-53(1999).
RN   [10]
RP   FUNCTION AS GLUCOSYLCERAMIDE BETA-1,4-GALACTOSYLTRANSFERASE.
RX   PubMed=24498430; DOI=10.1371/journal.pone.0088124;
RA   Yamaji T., Hanada K.;
RT   "Establishment of HeLa cell mutants deficient in sphingolipid-related genes
RT   using TALENs.";
RL   PLoS ONE 9:E88124-E88124(2014).
CC   -!- FUNCTION: Catalyzes the synthesis of lactosylceramide (LacCer) via the
CC       transfer of galactose from UDP-galactose to glucosylceramide (GlcCer)
CC       (PubMed:3099851, PubMed:1551920, PubMed:24498430). LacCer is the
CC       starting point in the biosynthesis of all gangliosides (membrane-bound
CC       glycosphingolipids) which play pivotal roles in the CNS including
CC       neuronal maturation and axonal and myelin formation (By similarity).
CC       {ECO:0000250|UniProtKB:Q9WVK5, ECO:0000269|PubMed:1551920,
CC       ECO:0000269|PubMed:24498430, ECO:0000269|PubMed:3099851}.
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:1551920, ECO:0000269|PubMed:24498430,
CC         ECO:0000269|PubMed:3099851};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31496;
CC         Evidence={ECO:0000305|PubMed:3099851};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000269|PubMed:3099851};
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:3099851};
CC   -!- ACTIVITY REGULATION: Inhibited by EDTA. {ECO:0000250|UniProtKB:O88419}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=3 uM for glucosylceramide {ECO:0000269|PubMed:3099851};
CC         KM=0.5 uM for UDP-galactose {ECO:0000269|PubMed:3099851};
CC         Vmax=0.06 nmol/h/mg enzyme toward glucosylceramide
CC         {ECO:0000269|PubMed:3099851};
CC         Vmax=86 nmol/h/mg enzyme toward UDP-galactose
CC         {ECO:0000269|PubMed:3099851};
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   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9UBX8-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9UBX8-2; Sequence=VSP_056554;
CC   -!- TISSUE SPECIFICITY: High expression in brain and adrenal gland, lower
CC       in liver, lung, colon and peripheral white blood cells.
CC   -!- SIMILARITY: Belongs to the glycosyltransferase 7 family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase;
CC       Note=Beta-1,4-galactosyltransferase 6;
CC       URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_441";
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DR   EMBL; AF038664; AAC39737.1; -; mRNA.
DR   EMBL; AF097159; AAD41695.1; -; mRNA.
DR   EMBL; AB024742; BAA76273.2; -; mRNA.
DR   EMBL; AC017100; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471088; EAX01269.1; -; Genomic_DNA.
DR   EMBL; BC069620; AAH69620.1; -; mRNA.
DR   EMBL; BC074835; AAH74835.1; -; mRNA.
DR   EMBL; BC074884; AAH74884.1; -; mRNA.
DR   CCDS; CCDS11900.1; -. [Q9UBX8-1]
DR   RefSeq; NP_001317499.1; NM_001330570.1.
DR   RefSeq; NP_004766.2; NM_004775.3. [Q9UBX8-1]
DR   AlphaFoldDB; Q9UBX8; -.
DR   SMR; Q9UBX8; -.
DR   BioGRID; 114740; 25.
DR   IntAct; Q9UBX8; 4.
DR   STRING; 9606.ENSP00000306459; -.
DR   SwissLipids; SLP:000001379; -. [Q9UBX8-1]
DR   CAZy; GT7; Glycosyltransferase Family 7.
DR   GlyCosmos; Q9UBX8; 8 sites, No reported glycans.
DR   GlyGen; Q9UBX8; 8 sites.
DR   iPTMnet; Q9UBX8; -.
DR   PhosphoSitePlus; Q9UBX8; -.
DR   BioMuta; B4GALT6; -.
DR   DMDM; 13123991; -.
DR   MassIVE; Q9UBX8; -.
DR   MaxQB; Q9UBX8; -.
DR   PaxDb; 9606-ENSP00000306459; -.
DR   PeptideAtlas; Q9UBX8; -.
DR   ProteomicsDB; 66651; -.
DR   ProteomicsDB; 84097; -. [Q9UBX8-1]
DR   Antibodypedia; 41869; 144 antibodies from 27 providers.
DR   DNASU; 9331; -.
DR   Ensembl; ENST00000306851.10; ENSP00000306459.5; ENSG00000118276.12. [Q9UBX8-1]
DR   Ensembl; ENST00000383131.3; ENSP00000372613.3; ENSG00000118276.12. [Q9UBX8-2]
DR   GeneID; 9331; -.
DR   KEGG; hsa:9331; -.
DR   MANE-Select; ENST00000306851.10; ENSP00000306459.5; NM_004775.5; NP_004766.2.
DR   UCSC; uc002kwz.5; human. [Q9UBX8-1]
DR   AGR; HGNC:929; -.
DR   CTD; 9331; -.
DR   DisGeNET; 9331; -.
DR   GeneCards; B4GALT6; -.
DR   HGNC; HGNC:929; B4GALT6.
DR   HPA; ENSG00000118276; Tissue enhanced (retina).
DR   MIM; 604017; gene.
DR   neXtProt; NX_Q9UBX8; -.
DR   OpenTargets; ENSG00000118276; -.
DR   PharmGKB; PA25228; -.
DR   VEuPathDB; HostDB:ENSG00000118276; -.
DR   eggNOG; KOG3916; Eukaryota.
DR   GeneTree; ENSGT00940000158138; -.
DR   InParanoid; Q9UBX8; -.
DR   OMA; VVWDCII; -.
DR   OrthoDB; 306273at2759; -.
DR   PhylomeDB; Q9UBX8; -.
DR   TreeFam; TF312834; -.
DR   BioCyc; MetaCyc:ENSG00000118276-MONOMER; -.
DR   BRENDA; 2.4.1.274; 2681.
DR   PathwayCommons; Q9UBX8; -.
DR   Reactome; R-HSA-2022854; Keratan sulfate biosynthesis.
DR   Reactome; R-HSA-913709; O-linked glycosylation of mucins.
DR   Reactome; R-HSA-975577; N-Glycan antennae elongation.
DR   SignaLink; Q9UBX8; -.
DR   UniPathway; UPA00378; -.
DR   BioGRID-ORCS; 9331; 14 hits in 1144 CRISPR screens.
DR   ChiTaRS; B4GALT6; human.
DR   GenomeRNAi; 9331; -.
DR   Pharos; Q9UBX8; Tbio.
DR   PRO; PR:Q9UBX8; -.
DR   Proteomes; UP000005640; Chromosome 18.
DR   RNAct; Q9UBX8; Protein.
DR   Bgee; ENSG00000118276; Expressed in lateral nuclear group of thalamus and 184 other cell types or tissues.
DR   ExpressionAtlas; Q9UBX8; 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:0000139; C:Golgi membrane; TAS:Reactome.
DR   GO; GO:0008378; F:galactosyltransferase activity; IDA:BHF-UCL.
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; ISS:UniProtKB.
DR   GO; GO:0021955; P:central nervous system neuron axonogenesis; ISS:UniProtKB.
DR   GO; GO:0010706; P:ganglioside biosynthetic process via lactosylceramide; ISS:UniProtKB.
DR   GO; GO:0006688; P:glycosphingolipid biosynthetic process; IBA:GO_Central.
DR   GO; GO:0070085; P:glycosylation; IBA:GO_Central.
DR   GO; GO:0001572; P:lactosylceramide biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0042551; P:neuron maturation; ISS:UniProtKB.
DR   GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
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; Q9UBX8; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Calcium; Disulfide bond; Glycoprotein;
KW   Glycosyltransferase; Golgi apparatus; Lipid biosynthesis; Lipid metabolism;
KW   Magnesium; Manganese; Membrane; Metal-binding; Reference proteome;
KW   Signal-anchor; Sphingolipid metabolism; Transferase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..382
FT                   /note="Beta-1,4-galactosyltransferase 6"
FT                   /id="PRO_0000080547"
FT   TOPO_DOM        1..14
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        15..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"
FT   VAR_SEQ         158..196
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_056554"
FT   VARIANT         379
FT                   /note="I -> V (in dbSNP:rs34683195)"
FT                   /id="VAR_054023"
FT   CONFLICT        194
FT                   /note="I -> V (in Ref. 1; AAC39737)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   382 AA;  44914 MW;  18E39920744ED643 CRC64;
     MSVLRRMMRV SNRSLLAFIF FFSLSSSCLY FIYVAPGIAN TYLFMVQARG IMLRENVKTI
     GHMIRLYTNK NSTLNGTDYP EGNNSSDYLV QTTTYLPENF TYSPYLPCPE KLPYMRGFLN
     VNVSEVSFDE IHQLFSKDLD IEPGGHWRPK DCKPRWKVAV LIPFRNRHEH LPIFFLHLIP
     MLQKQRLEFA FYVIEQTGTQ PFNRAMLFNV GFKEAMKDSV WDCVIFHDVD HLPENDRNYY
     GCGEMPRHFA AKLDKYMYIL PYKEFFGGVS GLTVEQFRKI NGFPNAFWGW GGEDDDLWNR
     VHYAGYNVTR PEGDLGKYKS IPHHHRGEVQ FLGRYKLLRY SKERQYIDGL NNLIYRPKIL
     VDRLYTNISV NLMPELAPIE DY
//