CEGT_RAT
ID CEGT_RAT Reviewed; 394 AA.
AC Q9R0E0; O55149;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Ceramide glucosyltransferase {ECO:0000305};
DE EC=2.4.1.80 {ECO:0000269|PubMed:10393098};
DE AltName: Full=GLCT-1;
DE AltName: Full=Glucosylceramide synthase;
DE Short=GCS;
DE AltName: Full=Glycosylceramide synthase;
DE AltName: Full=UDP-glucose ceramide glucosyltransferase;
DE AltName: Full=UDP-glucose:N-acylsphingosine D-glucosyltransferase;
GN Name=Ugcg {ECO:0000312|RGD:621870};
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]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND
RP MUTAGENESIS OF HIS-26; HIS-36; HIS-90; HIS-169; HIS-193; HIS-308; HIS-309;
RP 308-HIS-HIS-309 AND HIS-322.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=10393098; DOI=10.1042/bj3410395;
RA Wu K., Marks D.L., Watanabe R., Paul P., Rajan N., Pagano R.E.;
RT "Histidine-193 of rat glucosylceramide synthase resides in a UDP-
RT glucose- and inhibitor (D-threo-1-phenyl-2-decanoylamino-3-
RT morpholinopropan-1-ol)-binding region: a biochemical and mutational
RT study.";
RL Biochem. J. 341:395-400(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Liver;
RA Buenning C., Orci L., Hirabayashi Y., Wieland F.T., Jeckel D.;
RT "Purification and characterization of glucosylceramide synthase.";
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=1532799; DOI=10.1083/jcb.117.2.259;
RA Jeckel D., Karrenbauer A., Burger K.N., van Meer G., Wieland F.;
RT "Glucosylceramide is synthesized at the cytosolic surface of various Golgi
RT subfractions.";
RL J. Cell Biol. 117:259-267(1992).
RN [4]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=9867864; DOI=10.1074/jbc.274.1.451;
RA Marks D.L., Wu K., Paul P., Kamisaka Y., Watanabe R., Pagano R.E.;
RT "Oligomerization and topology of the Golgi membrane protein
RT glucosylceramide synthase.";
RL J. Biol. Chem. 274:451-456(1999).
RN [5]
RP ACTIVE SITE, AND MUTAGENESIS OF ASP-92; LYS-124; ASP-144; GLY-224; GLY-225;
RP GLU-235; ASP-236; GLY-247; ARG-272; ARG-275 AND TRP-276.
RX PubMed=11337504; DOI=10.1074/jbc.m102612200;
RA Marks D.L., Dominguez M., Wu K., Pagano R.E.;
RT "Identification of active site residues in glucosylceramide synthase. A
RT nucleotide-binding catalytic motif conserved with processive beta-
RT glycosyltransferases.";
RL J. Biol. Chem. 276:26492-26498(2001).
CC -!- FUNCTION: Participates in the initial step of the glucosylceramide-
CC based glycosphingolipid/GSL synthetic pathway at the cytosolic surface
CC of the Golgi. Catalyzes the transfer of glucose from UDP-glucose to
CC ceramide to produce glucosylceramide/GlcCer (such as beta-D-glucosyl-
CC (1<->1')-N-acylsphing-4-enine) (PubMed:10393098, PubMed:1532799).
CC Glucosylceramide is the core component of glycosphingolipids/GSLs,
CC amphipathic molecules consisting of a ceramide lipid moiety embedded in
CC the outer leaflet of the membrane, linked to one of hundreds of
CC different externally oriented oligosaccharide structures (By
CC similarity). Glycosphingolipids are essential components of membrane
CC microdomains that mediate membrane trafficking and signal transduction
CC (By similarity). They are implicated in many fundamental cellular
CC processes, including growth, differentiation, migration, morphogenesis,
CC cell-to-cell and cell-to-matrix interactions (By similarity). They are
CC required for instance in the proper development and functioning of the
CC nervous system. As an example of their role in signal transduction,
CC they regulate the leptin receptor/LEPR in the leptin-mediated signaling
CC pathway (By similarity). They also play an important role in the
CC establishment of the skin barrier regulating keratinocyte
CC differentiation and the proper assembly of the cornified envelope (By
CC similarity). The biosynthesis of GSLs is also required for the proper
CC intestinal endocytic uptake of nutritional lipids (By similarity).
CC Catalyzes the synthesis of xylosylceramide/XylCer (such as beta-D-
CC xylosyl-(1<->1')-N-acylsphing-4-enine) using UDP-Xyl as xylose donor
CC (By similarity). {ECO:0000250|UniProtKB:O88693,
CC ECO:0000250|UniProtKB:Q16739, ECO:0000269|PubMed:10393098,
CC ECO:0000269|PubMed:1532799}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphing-4-enine + UDP-alpha-D-glucose = a beta-D-
CC glucosyl-(1<->1')-N-acylsphing-4-enine + H(+) + UDP;
CC Xref=Rhea:RHEA:12088, ChEBI:CHEBI:15378, ChEBI:CHEBI:22801,
CC ChEBI:CHEBI:52639, ChEBI:CHEBI:58223, ChEBI:CHEBI:58885; EC=2.4.1.80;
CC Evidence={ECO:0000269|PubMed:10393098};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12089;
CC Evidence={ECO:0000305|PubMed:10393098};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphing-4-enine + UDP-alpha-D-xylose = a beta-D-
CC xylosyl-(1<->1')-N-acylsphing-4-enine + H(+) + UDP;
CC Xref=Rhea:RHEA:70243, ChEBI:CHEBI:15378, ChEBI:CHEBI:52639,
CC ChEBI:CHEBI:57632, ChEBI:CHEBI:58223, ChEBI:CHEBI:189068;
CC Evidence={ECO:0000250|UniProtKB:Q16739};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70244;
CC Evidence={ECO:0000250|UniProtKB:Q16739};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(9Z-octadecenoyl)-sphing-4-enine + UDP-alpha-D-xylose =
CC beta-D-xylosyl-(1<->1')-N-(9Z-octadecenoyl)-sphing-4-enine + H(+) +
CC UDP; Xref=Rhea:RHEA:70247, ChEBI:CHEBI:15378, ChEBI:CHEBI:57632,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:77996, ChEBI:CHEBI:189081;
CC Evidence={ECO:0000250|UniProtKB:Q16739};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70248;
CC Evidence={ECO:0000250|UniProtKB:Q16739};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000305|PubMed:10393098}.
CC -!- SUBUNIT: Interacts with RTN1; regulates the ceramide
CC glucosyltransferase activity of UGCG. {ECO:0000250|UniProtKB:Q16739}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:1532799, ECO:0000269|PubMed:9867864}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:9867864}.
CC -!- DOMAIN: The D1, D2, D3, (Q/R)XXRW motif is a critical part of the GCS
CC active site, involved in catalysis and UDP-sugar binding.
CC {ECO:0000305|PubMed:11337504}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 2 family. {ECO:0000305}.
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DR EMBL; AF047707; AAD02464.1; -; mRNA.
DR EMBL; AJ224156; CAA11853.1; -; mRNA.
DR RefSeq; NP_113983.1; NM_031795.2.
DR AlphaFoldDB; Q9R0E0; -.
DR SMR; Q9R0E0; -.
DR STRING; 10116.ENSRNOP00000021110; -.
DR SwissLipids; SLP:000000912; -.
DR CAZy; GT21; Glycosyltransferase Family 21.
DR PaxDb; Q9R0E0; -.
DR PRIDE; Q9R0E0; -.
DR Ensembl; ENSRNOT00000088872; ENSRNOP00000075148; ENSRNOG00000015644.
DR GeneID; 83626; -.
DR KEGG; rno:83626; -.
DR UCSC; RGD:621870; rat.
DR CTD; 7357; -.
DR RGD; 621870; Ugcg.
DR eggNOG; KOG2547; Eukaryota.
DR GeneTree; ENSGT00390000012898; -.
DR InParanoid; Q9R0E0; -.
DR OMA; HGSMPFH; -.
DR OrthoDB; 793389at2759; -.
DR PhylomeDB; Q9R0E0; -.
DR TreeFam; TF314564; -.
DR BRENDA; 2.4.1.80; 5301.
DR Reactome; R-RNO-1660662; Glycosphingolipid metabolism.
DR UniPathway; UPA00222; -.
DR PRO; PR:Q9R0E0; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000015644; Expressed in duodenum and 20 other tissues.
DR Genevisible; Q9R0E0; RN.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0008120; F:ceramide glucosyltransferase activity; IDA:RGD.
DR GO; GO:0102769; F:dihydroceramide glucosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0030154; P:cell differentiation; ISS:UniProtKB.
DR GO; GO:1903575; P:cornified envelope assembly; ISS:UniProtKB.
DR GO; GO:0061436; P:establishment of skin barrier; ISS:UniProtKB.
DR GO; GO:0006679; P:glucosylceramide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0098856; P:intestinal lipid absorption; ISS:UniProtKB.
DR GO; GO:0030216; P:keratinocyte differentiation; ISS:UniProtKB.
DR GO; GO:0033210; P:leptin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0048666; P:neuron development; ISS:UniProtKB.
DR GO; GO:0006497; P:protein lipidation; ISS:UniProtKB.
DR GO; GO:0009966; P:regulation of signal transduction; ISS:UniProtKB.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR025993; Ceramide_glucosylTrfase.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR12726; PTHR12726; 1.
DR Pfam; PF13506; Glyco_transf_21; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Acetylation; Glycosyltransferase; Golgi apparatus; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Reference proteome; Sphingolipid metabolism;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..394
FT /note="Ceramide glucosyltransferase"
FT /id="PRO_0000059178"
FT TOPO_DOM 1..10
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:10393098"
FT TRANSMEM 11..32
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..195
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10393098"
FT TRANSMEM 196..215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 216..287
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:10393098"
FT TRANSMEM 288..304
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 305..309
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10393098"
FT TRANSMEM 310..328
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 329..348
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:10393098"
FT TRANSMEM 349..369
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 370..394
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10393098"
FT MOTIF 92
FT /note="D1"
FT /evidence="ECO:0000305"
FT MOTIF 144
FT /note="D2"
FT /evidence="ECO:0000305"
FT MOTIF 236
FT /note="D3"
FT /evidence="ECO:0000305"
FT MOTIF 272..276
FT /note="(Q/R)XXRW"
FT /evidence="ECO:0000305"
FT ACT_SITE 236
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:11337504"
FT SITE 193
FT /note="May play an important role in binding to the
FT inhibitors DEPC and PDMP"
FT /evidence="ECO:0000269|PubMed:10393098"
FT MOD_RES 117
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88693"
FT VARIANT 8
FT /note="Q -> L (in strain: Wistar)"
FT VARIANT 89
FT /note="D -> G (in strain: Wistar)"
FT VARIANT 153
FT /note="T -> S (in strain: Wistar)"
FT VARIANT 179
FT /note="G -> A (in strain: Wistar)"
FT VARIANT 387
FT /note="T -> I (in strain: Wistar)"
FT MUTAGEN 26
FT /note="H->A: Inhibits activity to less than 6%."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 26
FT /note="H->D: Inhibits activity to about 10%."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 26
FT /note="H->N: Inhibits activity to about 50%."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 26
FT /note="H->R: No effect on activity. Decreased sensitivity
FT to the inhibitor PDMP."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 36
FT /note="H->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 90
FT /note="H->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 92
FT /note="D->A: Inhibits activity to about 20%."
FT /evidence="ECO:0000269|PubMed:11337504"
FT MUTAGEN 124
FT /note="K->A: Completely abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:11337504"
FT MUTAGEN 144
FT /note="D->A: Completely abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:11337504"
FT MUTAGEN 169
FT /note="H->A: Inhibits activity to about 30%. Decreased
FT sensitivity to PDMP."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 193
FT /note="H->A: Inhibits activity to about 30%. Insensitive to
FT the inhibitors DEPC and PDMP."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 193
FT /note="H->D: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 193
FT /note="H->N: Inhibits activity to about 20%. Insensitive to
FT the inhibitors DEPC and PDMP."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 193
FT /note="H->R: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 224
FT /note="G->I: Completely abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:11337504"
FT MUTAGEN 225
FT /note="G->I: Completely abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:11337504"
FT MUTAGEN 235
FT /note="E->A: Inhibits activity to less than 1.5%."
FT /evidence="ECO:0000269|PubMed:11337504"
FT MUTAGEN 236
FT /note="D->A: Completely abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:11337504"
FT MUTAGEN 247
FT /note="G->I: Leads to near complete loss of activity."
FT /evidence="ECO:0000269|PubMed:11337504"
FT MUTAGEN 272
FT /note="R->A: Completely abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:11337504"
FT MUTAGEN 275
FT /note="R->A: Completely abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:11337504"
FT MUTAGEN 276
FT /note="W->A: Completely abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:11337504"
FT MUTAGEN 308..309
FT /note="HH->AA: Inhibits activity to about 10%."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 308
FT /note="H->A: Inhibits activity to about 35%."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 309
FT /note="H->A: Inhibits activity to about 70%."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 322
FT /note="H->A: Inhibits activity to less than 6%."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 322
FT /note="H->D: Inhibits activity to less than 6%."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 322
FT /note="H->N: Inhibits activity to about 50%."
FT /evidence="ECO:0000269|PubMed:10393098"
FT MUTAGEN 322
FT /note="H->R: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:10393098"
SQ SEQUENCE 394 AA; 44823 MW; 214581C0B8D9152C CRC64;
MALLDLAQEG MALFGFVLFV VLWLMHFMSI IYTRLHLNKK ATDKQPYSKL PGVSLLKPLK
GVDPNLINNL ETFFELDYPK YEVLLCVQDH DDPAIEVCKK LLGKYPNVDA RLFIGGKKVG
INPKINNLMP AYEVAKYDLI WICDSGIRVI PDTLTDMVNQ MTERVGLVHG LPYVADRQGF
AATLEQVYFG TSHPRSYISA NVTGFKCVTG MSCLMRKDVL DQAGGLIAFA QYIAEDYFMA
KAIADRGWKF SMSTQVAMQN SGSYSISQFQ SRMIRWTKLR INMLPATIIC EPISECFVAS
LIIGWAAHHV FRWDIMVFFM CHCLAWFIFD YIQLRGVQGG TLCFSKLDYA VAWFIRESMT
IYIFLSALWD PTISWRAGRY RLRCGGTAEE ILDV
