A4GAT_RAT
ID A4GAT_RAT Reviewed; 360 AA.
AC Q9JI93; Q4QR98;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Lactosylceramide 4-alpha-galactosyltransferase;
DE EC=2.4.1.228 {ECO:0000269|PubMed:10854428};
DE AltName: Full=Alpha-1,4-N-acetylglucosaminyltransferase;
DE AltName: Full=Alpha-1,4-galactosyltransferase;
DE AltName: Full=Alpha4Gal-T1;
DE AltName: Full=Globotriaosylceramide synthase;
DE Short=Gb3 synthase;
DE AltName: Full=UDP-galactose:beta-D-galactosyl-beta1-R 4-alpha-D-galactosyltransferase;
GN Name=A4galt {ECO:0000312|RGD:621583};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAF82758.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF 199-ASP--ASP-201.
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAF82758.1};
RC TISSUE=Placenta {ECO:0000312|EMBL:AAF82758.1};
RX PubMed=10854428; DOI=10.1074/jbc.m002630200;
RA Keusch J.J., Manzella S.M., Nyame K.A., Cummings R.D., Baenziger J.U.;
RT "Cloning of Gb3 synthase, the key enzyme in globo-series glycosphingolipid
RT synthesis, predicts a family of alpha1,4-glycosyltransferases conserved in
RT plants, insects and mammals.";
RL J. Biol. Chem. 275:25315-25321(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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).
CC -!- FUNCTION: Catalyzes the transfer of galactose from UDP-alpha-D-
CC galactose to lactosylceramide/beta-D-galactosyl-(1->4)-beta-D-glucosyl-
CC (1<->1)-ceramide(d18:1(4E)) to produce globotriaosylceramide/globoside
CC Gb3Cer (d18:1(4E)) (PubMed:10854428). Also able to transfer galactose
CC to galactosylceramide/beta-D-Gal-(1<->1')-Cer (By similarity).
CC Globoside Gb3Cer is a glycosphingolipid of the globo serie, one of the
CC major types of neutral root structures of glycosphingolipids, that
CC constitute a significant portion of mammalian cell membranes (By
CC similarity). {ECO:0000250|UniProtKB:Q9NPC4,
CC ECO:0000269|PubMed:10854428}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)-Cer(d18:1(4E)) + UDP-
CC alpha-D-galactose = globoside Gb3Cer (d18:1(4E)) + H(+) + UDP;
CC Xref=Rhea:RHEA:11924, ChEBI:CHEBI:15378, ChEBI:CHEBI:17950,
CC ChEBI:CHEBI:18313, ChEBI:CHEBI:58223, ChEBI:CHEBI:66914;
CC EC=2.4.1.228; Evidence={ECO:0000269|PubMed:10854428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11925;
CC Evidence={ECO:0000305|PubMed:10854428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-Gal-(1<->1')-Cer + UDP-alpha-D-galactose = alpha-D-Gal-
CC (1->4)-beta-D-Gal-(1<->1')-Cer + H(+) + UDP; Xref=Rhea:RHEA:60044,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58223, ChEBI:CHEBI:66914,
CC ChEBI:CHEBI:143593, ChEBI:CHEBI:143594;
CC Evidence={ECO:0000250|UniProtKB:Q9NPC4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60045;
CC Evidence={ECO:0000250|UniProtKB:Q9NPC4};
CC -!- PATHWAY: Glycolipid biosynthesis. {ECO:0000305|PubMed:10854428}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in kidney, mesenteric
CC lymph node, spleen and brain. {ECO:0000269|PubMed:10854428}.
CC -!- DOMAIN: The conserved DXD motif is involved in enzyme activity.
CC {ECO:0000269|PubMed:10854428}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 32 family.
CC {ECO:0000305}.
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DR EMBL; AF248544; AAF82758.1; -; mRNA.
DR EMBL; BC097323; AAH97323.1; -; mRNA.
DR RefSeq; NP_071576.1; NM_022240.2.
DR RefSeq; XP_006242179.1; XM_006242117.3.
DR RefSeq; XP_006242180.1; XM_006242118.3.
DR RefSeq; XP_017450568.1; XM_017595079.1.
DR RefSeq; XP_017450569.1; XM_017595080.1.
DR RefSeq; XP_017450570.1; XM_017595081.1.
DR AlphaFoldDB; Q9JI93; -.
DR STRING; 10116.ENSRNOP00000064362; -.
DR SwissLipids; SLP:000000761; -.
DR SwissLipids; SLP:000000762; -.
DR CAZy; GT32; Glycosyltransferase Family 32.
DR GlyGen; Q9JI93; 2 sites.
DR PhosphoSitePlus; Q9JI93; -.
DR jPOST; Q9JI93; -.
DR PaxDb; Q9JI93; -.
DR Ensembl; ENSRNOT00000012914; ENSRNOP00000064362; ENSRNOG00000009736.
DR Ensembl; ENSRNOT00000096640; ENSRNOP00000095592; ENSRNOG00000009736.
DR Ensembl; ENSRNOT00000104849; ENSRNOP00000084868; ENSRNOG00000009736.
DR Ensembl; ENSRNOT00000108253; ENSRNOP00000081935; ENSRNOG00000009736.
DR GeneID; 63888; -.
DR KEGG; rno:63888; -.
DR UCSC; RGD:621583; rat.
DR CTD; 53947; -.
DR RGD; 621583; A4galt.
DR eggNOG; KOG1928; Eukaryota.
DR GeneTree; ENSGT00510000047981; -.
DR HOGENOM; CLU_049512_2_0_1; -.
DR InParanoid; Q9JI93; -.
DR OMA; AFYPIRW; -.
DR OrthoDB; 1082380at2759; -.
DR PhylomeDB; Q9JI93; -.
DR PRO; PR:Q9JI93; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000009736; Expressed in jejunum and 12 other tissues.
DR Genevisible; Q9JI93; RN.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0008378; F:galactosyltransferase activity; IDA:RGD.
DR GO; GO:0016758; F:hexosyltransferase activity; IBA:GO_Central.
DR GO; GO:0050512; F:lactosylceramide 4-alpha-galactosyltransferase activity; ISO:RGD.
DR GO; GO:0015643; F:toxic substance binding; ISO:RGD.
DR GO; GO:0001576; P:globoside biosynthetic process; ISO:RGD.
DR GO; GO:0006688; P:glycosphingolipid biosynthetic process; IBA:GO_Central.
DR GO; GO:0007009; P:plasma membrane organization; ISO:RGD.
DR InterPro; IPR007652; A1-4-GlycosylTfrase_dom.
DR InterPro; IPR007577; GlycoTrfase_DXD_sugar-bd_CS.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR Pfam; PF04572; Gb3_synth; 1.
DR Pfam; PF04488; Gly_transf_sug; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Glycosyltransferase; Golgi apparatus; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Reference proteome; Signal-anchor; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..360
FT /note="Lactosylceramide 4-alpha-galactosyltransferase"
FT /id="PRO_0000080582"
FT TOPO_DOM 1..30
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 31..51
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 52..360
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT MOTIF 199..201
FT /note="DXD motif"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 316
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 199..201
FT /note="DTD->ATA: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10854428"
SQ SEQUENCE 360 AA; 41551 MW; 0A4181886DB49D6A CRC64;
MGISRSDLEE TMSKPPDCLP RMLRGTPRQR VFTLFIISFK FTFLVSILIY WHTVGAPKDQ
RRQYSLPVDF PCPQLAFPRV SAPGNIFFLE TSDRTNPSFL FMCSVESAAR AHPESQVVVL
MKGLPRDTTA WPRNLGISLL SCFPNVQIRP LDLQELFEDT PLAAWYLEAQ HRWEPYLLPV
LSDASRIALL WKFGGIYLDT DFIVLKNLRN LTNMLGIQSR YVLNGAFLAF ERKHEFLALC
IRDFVAHYNG WIWGHQGPQL LTRVFKKWCS IHSLKESRAC RGVTALPPEA FYPIPWQNWK
KYFEDVSPEE LAQLLNATYA VHVWNKKSQG THLEATSRAL LAQLHARYCP TTHRAMTMYL
