B4GT5_MOUSE
ID B4GT5_MOUSE Reviewed; 388 AA.
AC Q9JMK0; A2A5T7;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Beta-1,4-galactosyltransferase 5 {ECO:0000305};
DE Short=Beta-1,4-GalTase 5;
DE Short=Beta4Gal-T5;
DE Short=b4Gal-T5;
DE EC=2.4.1.-;
DE AltName: Full=Beta-1,4-GalT II {ECO:0000250|UniProtKB:O43286};
DE AltName: Full=Glucosylceramide beta-1,4-galactosyltransferase;
DE EC=2.4.1.274 {ECO:0000269|PubMed:20574042, ECO:0000269|PubMed:21057870, ECO:0000269|PubMed:23882130, ECO:0000269|PubMed:30114188};
DE AltName: Full=Lactosylceramide synthase {ECO:0000303|PubMed:20574042, ECO:0000303|PubMed:23882130, ECO:0000303|PubMed:30114188};
DE Short=LacCer synthase {ECO:0000303|PubMed:20574042, ECO:0000303|PubMed:23882130, ECO:0000303|PubMed:30114188};
DE AltName: Full=UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 5;
DE AltName: Full=UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 5;
GN Name=B4galt5 {ECO:0000312|MGI:MGI:1927169}; Synonyms=Bgt-5;
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], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=11145975; DOI=10.1046/j.1471-4159.2001.00004.x;
RA Nakamura N., Yamakawa N., Sato T., Tojo H., Tachi C., Furukawa K.;
RT "Differential gene expression of beta-1,4-galactosyltransferases I, II and
RT V during mouse brain development.";
RL J. Neurochem. 76:29-38(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION IN EARLY EMBRYOGENESIS, FUNCTION AS GLUCOSYLCERAMIDE
RP BETA-1,4-GALACTOSYLTRANSFERASE, CATALYTIC ACTIVITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=20574042; DOI=10.1093/glycob/cwq098;
RA Nishie T., Hikimochi Y., Zama K., Fukusumi Y., Ito M., Yokoyama H.,
RA Naruse C., Ito M., Asano M.;
RT "Beta4-galactosyltransferase-5 is a lactosylceramide synthase essential for
RT mouse extra-embryonic development.";
RL Glycobiology 20:1311-1322(2010).
RN [5]
RP FUNCTION AS GLUCOSYLCERAMIDE BETA-1,4-GALACTOSYLTRANSFERASE, AND CATALYTIC
RP ACTIVITY.
RX PubMed=21057870; DOI=10.1007/s10719-010-9313-2;
RA Kumagai T., Sato T., Natsuka S., Kobayashi Y., Zhou D., Shinkai T.,
RA Hayakawa S., Furukawa K.;
RT "Involvement of murine beta-1,4-galactosyltransferase V in lactosylceramide
RT biosynthesis.";
RL Glycoconj. J. 27:685-695(2010).
RN [6]
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 [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=29415997; DOI=10.1038/s41419-017-0239-5;
RA Li S.F., Zhu C.S., Wang Y.M., Xie X.X., Xiao L.L., Zhang Z.C., Tang Q.Q.,
RA Li X.;
RT "Downregulation of beta1,4-galactosyltransferase 5 improves insulin
RT resistance by promoting adipocyte commitment and reducing inflammation.";
RL Cell Death Dis. 9:196-196(2018).
RN [8]
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:21057870, PubMed:23882130, PubMed:30114188). 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 (PubMed:30114188).
CC Plays a role in the glycosylation of BMPR1A and regulation of its
CC protein stability (PubMed:29415997). Essential for extraembryonic
CC development during early embryogenesis (PubMed:20574042,
CC PubMed:21057870). {ECO:0000269|PubMed:20574042,
CC ECO:0000269|PubMed:21057870, ECO:0000269|PubMed:23882130,
CC ECO:0000269|PubMed:29415997, 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:20574042, ECO:0000269|PubMed:21057870,
CC 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:Q9UBX8};
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 Golgi apparatus {ECO:0000250|UniProtKB:A0A1S6M251}. Note=Trans
CC cisternae of Golgi stack. {ECO:0000250|UniProtKB:P15291}.
CC -!- TISSUE SPECIFICITY: Highest levels in heart, brain, liver and kidney
CC with lower levels in spleen, lung and testis.
CC {ECO:0000269|PubMed:11145975, ECO:0000269|PubMed:23882130}.
CC -!- DEVELOPMENTAL STAGE: In the brain, expression increases after birth.
CC {ECO:0000269|PubMed:11145975}.
CC -!- INDUCTION: Up-regulated in subcutaneous adipose tissue during obesity
CC and diabetes (at protein level). {ECO:0000269|PubMed:29415997}.
CC -!- DISRUPTION PHENOTYPE: Single knockout mice show early embryonic
CC lethality (PubMed:20574042). Mice with conditional knockout in
CC embryonic fibroblasts are born normally, grow to adulthood without
CC apparent abnormalities but have reduced glucosylceramide beta-1,4-
CC galactosyltransferase activity (PubMed:30114188). Double knockout mice
CC of B4GALT5 and B4GALT6 genes develop normally during embryogenesis and
CC perinatal stage (PubMed:30114188). However, they show growth
CC retardation and motor deficits with hindlimb dysfunction at 2 weeks of
CC age, and they all die by 4 weeks of age (PubMed:30114188). Axonal and
CC myelin formation are remarkably impaired in the spinal cords and
CC 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 brain
CC (PubMed:30114188). Knockdown in subcutaneous adipose tissue alleviates
CC insulin resistance and adipose tissue inflammation, increases
CC adipogenesis in high-fat diet (HFD)-fed mice and ob/ob mice and reduces
CC the glycosylation of BMPR1A (PubMed:29415997).
CC {ECO:0000269|PubMed:20574042, ECO:0000269|PubMed:29415997,
CC ECO:0000269|PubMed:30114188}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 7 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=b4GalT5;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_mou_464";
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DR EMBL; AB004786; BAA94791.1; -; mRNA.
DR EMBL; AL591762; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591854; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466551; EDL06506.1; -; Genomic_DNA.
DR CCDS; CCDS17098.1; -.
DR RefSeq; NP_062809.2; NM_019835.2.
DR AlphaFoldDB; Q9JMK0; -.
DR SMR; Q9JMK0; -.
DR BioGRID; 207911; 1.
DR STRING; 10090.ENSMUSP00000104844; -.
DR SwissLipids; SLP:000000786; -.
DR CAZy; GT7; Glycosyltransferase Family 7.
DR GlyGen; Q9JMK0; 7 sites.
DR PhosphoSitePlus; Q9JMK0; -.
DR EPD; Q9JMK0; -.
DR MaxQB; Q9JMK0; -.
DR PaxDb; Q9JMK0; -.
DR PRIDE; Q9JMK0; -.
DR ProteomicsDB; 273527; -.
DR Antibodypedia; 28497; 176 antibodies from 26 providers.
DR DNASU; 56336; -.
DR Ensembl; ENSMUST00000109221; ENSMUSP00000104844; ENSMUSG00000017929.
DR GeneID; 56336; -.
DR KEGG; mmu:56336; -.
DR UCSC; uc008nzm.1; mouse.
DR CTD; 9334; -.
DR MGI; MGI:1927169; B4galt5.
DR VEuPathDB; HostDB:ENSMUSG00000017929; -.
DR eggNOG; KOG3916; Eukaryota.
DR GeneTree; ENSGT00940000158019; -.
DR HOGENOM; CLU_044391_6_0_1; -.
DR InParanoid; Q9JMK0; -.
DR OMA; MSEISMD; -.
DR OrthoDB; 1201618at2759; -.
DR PhylomeDB; Q9JMK0; -.
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; 56336; 6 hits in 73 CRISPR screens.
DR ChiTaRS; B4galt5; mouse.
DR PRO; PR:Q9JMK0; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9JMK0; protein.
DR Bgee; ENSMUSG00000017929; Expressed in gastrula and 237 other tissues.
DR ExpressionAtlas; Q9JMK0; baseline and differential.
DR Genevisible; Q9JMK0; 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; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003945; F:N-acetyllactosamine synthase activity; IMP:MGI.
DR GO; GO:0008489; F:UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity; IMP:UniProtKB.
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:0009101; P:glycoprotein biosynthetic process; IBA:GO_Central.
DR GO; GO:0070085; P:glycosylation; IBA:GO_Central.
DR GO; GO:0042551; P:neuron maturation; IMP:UniProtKB.
DR GO; GO:0030311; P:poly-N-acetyllactosamine biosynthetic process; IMP:MGI.
DR GO; GO:0040019; P:positive regulation of embryonic development; IMP:UniProtKB.
DR GO; GO:0006486; P:protein glycosylation; IMP:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB.
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 Disulfide bond; Glycoprotein; Glycosyltransferase; Golgi apparatus;
KW Lipid biosynthesis; Lipid metabolism; Manganese; Membrane; Metal-binding;
KW Reference proteome; Signal-anchor; Sphingolipid metabolism; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..388
FT /note="Beta-1,4-galactosyltransferase 5"
FT /id="PRO_0000080546"
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..388
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT BINDING 169..173
FT /ligand="UDP-alpha-D-galactose"
FT /ligand_id="ChEBI:CHEBI:66914"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 208..210
FT /ligand="UDP-alpha-D-galactose"
FT /ligand_id="ChEBI:CHEBI:66914"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 235..236
FT /ligand="UDP-alpha-D-galactose"
FT /ligand_id="ChEBI:CHEBI:66914"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 236
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 264
FT /ligand="UDP-alpha-D-galactose"
FT /ligand_id="ChEBI:CHEBI:66914"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 296
FT /ligand="UDP-alpha-D-galactose"
FT /ligand_id="ChEBI:CHEBI:66914"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 298..301
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 329..330
FT /ligand="UDP-alpha-D-galactose"
FT /ligand_id="ChEBI:CHEBI:66914"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 329
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT BINDING 340
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000250|UniProtKB:Q9UBV7"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 360
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 364
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 373
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 114..158
FT /evidence="ECO:0000250|UniProtKB:P15291"
FT DISULFID 229..248
FT /evidence="ECO:0000250|UniProtKB:P15291"
FT CONFLICT 192
FT /note="R -> A (in Ref. 1; BAA94791)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 388 AA; 44814 MW; FB3D6FBA2F8B3775 CRC64;
MRARRGLLRL PRRSLLAALF FFSLSSSLLY FVYVAPGIVN TYLFMVQAQG ILLRDNVRTI
GAQVYEQVVR SAYAKRNSSL NDSDYPLDLN HSEAFPPTTT FLPEDFTYFA NHPCPERLPS
MKGPIDINMS EIAMDDIHEL FSRDPAIKLG GHWKPADCVP RWKVAILIPF RNRHEHLPVL
LRHLLPMLQR QRLQFAFYVI EQVGTQPFNR AMLFNVGFQE AMKDLDWDCL IFHDVDHIPE
SDRNYYGCGQ MPRHFATKLD KYMYLLPYTE FFGGVSGLTV EQFRKINGFP NAFWGWGGED
DDLWNRVQNA GYSVSRPEGD TGKYKSIPHH HRGEVQFLGR YALLRKSKER QGLDGLNNLN
YSANVTYDAL YKNITVNLTP ELAQVTEY
