B4GT6_HUMAN
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 03-AUG-2022, entry version 174.
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; Note=Beta-1,4-
CC 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 GlyGen; Q9UBX8; 8 sites.
DR iPTMnet; Q9UBX8; -.
DR PhosphoSitePlus; Q9UBX8; -.
DR BioMuta; B4GALT6; -.
DR DMDM; 13123991; -.
DR MassIVE; Q9UBX8; -.
DR MaxQB; Q9UBX8; -.
DR PaxDb; Q9UBX8; -.
DR PeptideAtlas; Q9UBX8; -.
DR PRIDE; Q9UBX8; -.
DR Antibodypedia; 41869; 121 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 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; NFTYSPF; -.
DR OrthoDB; 1201618at2759; -.
DR PhylomeDB; Q9UBX8; -.
DR TreeFam; TF312834; -.
DR BioCyc; MetaCyc:ENSG00000118276-MON; -.
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; 12 hits in 1067 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 182 other tissues.
DR ExpressionAtlas; Q9UBX8; baseline and differential.
DR Genevisible; Q9UBX8; HS.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 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 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
