CGT3_CAEEL
ID CGT3_CAEEL Reviewed; 459 AA.
AC Q21054; G5EET1; G5EGR9; Q8T3D8;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Ceramide glucosyltransferase 3;
DE Short=CGT-3 {ECO:0000303|PubMed:19240113, ECO:0000303|PubMed:21325339};
DE EC=2.4.1.80 {ECO:0000269|PubMed:21325339};
GN Name=cgt-3 {ECO:0000312|WormBase:F59G1.1a};
GN ORFNames=F59G1.1 {ECO:0000312|WormBase:F59G1.1a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND D).
RC STRAIN=Bristol N2;
RX PubMed=17174523; DOI=10.1016/j.ygeno.2006.10.007;
RA Vazquez-Manrique R.P., Gonzalez-Cabo P., Ortiz-Martin I., Ros S.,
RA Baylis H.A., Palau F.;
RT "The frataxin-encoding operon of Caenorhabditis elegans shows complex
RT structure and regulation.";
RL Genomics 89:392-401(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION.
RX PubMed=7651085; DOI=10.1007/bf02537032;
RA Chitwood D.J., Lusby W.R., Thompson M.J., Kochansky J.P., Howarth O.W.;
RT "The glycosylceramides of the nematode Caenorhabditis elegans contain an
RT unusual, branched-chain sphingoid base.";
RL Lipids 30:567-573(1995).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RX PubMed=19240113; DOI=10.1242/jcs.042754;
RA Marza E., Simonsen K.T., Faergeman N.J., Lesa G.M.;
RT "Expression of ceramide glucosyltransferases, which are essential for
RT glycosphingolipid synthesis, is only required in a small subset of C.
RT elegans cells.";
RL J. Cell Sci. 122:822-833(2009).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=21325339; DOI=10.1093/glycob/cwr019;
RA Nomura K.H., Murata D., Hayashi Y., Dejima K., Mizuguchi S.,
RA Kage-Nakadai E., Gengyo-Ando K., Mitani S., Hirabayashi Y., Ito M.,
RA Nomura K.;
RT "Ceramide glucosyltransferase of the nematode Caenorhabditis elegans is
RT involved in oocyte formation and in early embryonic cell division.";
RL Glycobiology 21:834-848(2011).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26115433; DOI=10.1371/journal.pone.0130778;
RA Zhu M., Wu G., Li Y.X., Stevens J.K., Fan C.X., Spang A., Dong M.Q.;
RT "Serum- and Glucocorticoid-Inducible Kinase-1 (SGK-1) Plays a Role in
RT Membrane Trafficking in Caenorhabditis elegans.";
RL PLoS ONE 10:e0130778-e0130778(2015).
RN [7]
RP ERRATUM.
RX PubMed=27631731; DOI=10.1371/journal.pone.0163398;
RA Zhu M., Wu G., Li Y.X., Stevens J.K., Fan C.X., Spang A., Dong M.Q.;
RT "Correction: Serum- and Glucocorticoid-Inducible Kinase-1 (SGK-1) Plays a
RT Role in Membrane Trafficking in Caenorhabditis elegans.";
RL PLoS ONE 11:e0163398-e0163398(2016).
CC -!- FUNCTION: Catalyzes the first glycosylation step in glycosphingolipid
CC biosynthesis, the transfer of glucose to ceramide to produce
CC glucosylceramides (GlcCer). GlcCer are known to contribute to the
CC physical properties and physiological functions of membranes and may
CC regulate signal transduction. Seems to be the major active form in the
CC nematode (PubMed:19240113, PubMed:21325339). Only branched-chain
CC sphingoid bases like 15-methylhexadecasphing-4-enine are used for
CC generating complex sphingolipids in Caenorhabditis elegans
CC (PubMed:7651085). Together with cgt-1, plays a role in the trafficking
CC of proteins such as mig-14 to the cell membrane in intestinal cells
CC (PubMed:26115433). {ECO:0000269|PubMed:19240113,
CC ECO:0000269|PubMed:21325339, ECO:0000269|PubMed:26115433,
CC ECO:0000269|PubMed:7651085}.
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:21325339};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12089;
CC Evidence={ECO:0000269|PubMed:21325339};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-acyl-15-methylhexadecasphing-4-enine + UDP-alpha-D-glucose =
CC H(+) + N-acyl-1-beta-D-glucosyl-15-methylhexadecasphing-4-enine +
CC UDP; Xref=Rhea:RHEA:34611, ChEBI:CHEBI:15378, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:58885, ChEBI:CHEBI:70815, ChEBI:CHEBI:70846;
CC Evidence={ECO:0000305|PubMed:19240113, ECO:0000305|PubMed:21325339};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34612;
CC Evidence={ECO:0000305|PubMed:19240113, ECO:0000305|PubMed:21325339};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:19240113, ECO:0000269|PubMed:21325339}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:F59G1.1a};
CC IsoId=Q21054-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:F59G1.1b};
CC IsoId=Q21054-2; Sequence=VSP_045384;
CC Name=d {ECO:0000312|WormBase:F59G1.1d};
CC IsoId=Q21054-4; Sequence=VSP_045383;
CC -!- TISSUE SPECIFICITY: Expressed in pharyngeal intestinal valve,
CC intestinal rectal valve and hypodermis. {ECO:0000305|PubMed:19240113,
CC ECO:0000305|PubMed:21325339}.
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:0000250|UniProtKB:Q9R0E0}.
CC -!- DISRUPTION PHENOTYPE: Reduced brood size. Reduced glucosyl-ceramide
CC content and expression at cell surface. Increased expression of
CC sphingomyelins and sphingomyelin clustering at cell surface. Loss of
CC function in the germline leads to defects in oocyte formation and early
CC embryonic divisions and shortened body length. Loss of function in
CC somatic cells may lead to L1 arrest (PubMed:19240113, PubMed:21325339).
CC Double RNAi-mediated knockdown together with cgt-1 reduces the rate of
CC development and restores the basolateral cell membrane localization of
CC mig-14 in intestinal cells in a sgk-1 ok538 mutant background
CC (PubMed:26115433). {ECO:0000269|PubMed:19240113,
CC ECO:0000269|PubMed:21325339, ECO:0000269|PubMed:26115433}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 2 family. {ECO:0000305}.
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DR EMBL; DQ178632; ABD75711.1; -; mRNA.
DR EMBL; DQ178633; ABD75712.1; -; mRNA.
DR EMBL; DQ178634; ABD75713.1; -; mRNA.
DR EMBL; BX284602; CCD70149.1; -; Genomic_DNA.
DR EMBL; BX284602; CCD70150.1; -; Genomic_DNA.
DR EMBL; BX284602; CCD70152.1; -; Genomic_DNA.
DR RefSeq; NP_495181.2; NM_062780.5. [Q21054-2]
DR RefSeq; NP_495182.2; NM_062781.4. [Q21054-1]
DR RefSeq; NP_871996.1; NM_182196.3.
DR AlphaFoldDB; Q21054; -.
DR STRING; 6239.F59G1.1b.2; -.
DR SwissLipids; SLP:000000023; -.
DR CAZy; GT21; Glycosyltransferase Family 21.
DR EPD; Q21054; -.
DR PaxDb; Q21054; -.
DR PeptideAtlas; Q21054; -.
DR EnsemblMetazoa; F59G1.1a.1; F59G1.1a.1; WBGene00019127. [Q21054-1]
DR EnsemblMetazoa; F59G1.1b.1; F59G1.1b.1; WBGene00019127. [Q21054-2]
DR EnsemblMetazoa; F59G1.1b.2; F59G1.1b.2; WBGene00019127. [Q21054-2]
DR EnsemblMetazoa; F59G1.1d.1; F59G1.1d.1; WBGene00019127. [Q21054-4]
DR GeneID; 174001; -.
DR KEGG; cel:CELE_F59G1.1; -.
DR UCSC; F59G1.1b.1; c. elegans.
DR CTD; 174001; -.
DR WormBase; F59G1.1a; CE29810; WBGene00019127; cgt-3. [Q21054-1]
DR WormBase; F59G1.1b; CE29811; WBGene00019127; cgt-3. [Q21054-2]
DR WormBase; F59G1.1d; CE33409; WBGene00019127; cgt-3. [Q21054-4]
DR eggNOG; KOG2547; Eukaryota.
DR GeneTree; ENSGT00390000012898; -.
DR InParanoid; Q21054; -.
DR OMA; HGSMPFH; -.
DR OrthoDB; 793389at2759; -.
DR UniPathway; UPA00222; -.
DR PRO; PR:Q21054; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00019127; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0008120; F:ceramide glucosyltransferase activity; IBA:GO_Central.
DR GO; GO:0102769; F:dihydroceramide glucosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006679; P:glucosylceramide biosynthetic process; IGI:WormBase.
DR GO; GO:0002119; P:nematode larval development; IGI:WormBase.
DR GO; GO:0042661; P:regulation of mesodermal cell fate specification; IMP:UniProtKB.
DR GO; GO:1904508; P:regulation of protein localization to basolateral plasma membrane; IGI:WormBase.
DR GO; GO:1901048; P:transforming growth factor beta receptor signaling pathway involved in regulation of multicellular organism growth; IMP: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 Alternative splicing; Glycosyltransferase; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Reference proteome; Sphingolipid metabolism;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..459
FT /note="Ceramide glucosyltransferase 3"
FT /id="PRO_0000421283"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 367..387
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 415..435
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 156
FT /note="D1"
FT /evidence="ECO:0000305"
FT MOTIF 208
FT /note="D2"
FT /evidence="ECO:0000305"
FT MOTIF 302
FT /note="D3"
FT /evidence="ECO:0000305"
FT MOTIF 338..342
FT /note="(Q/R)XXRW"
FT /evidence="ECO:0000305"
FT ACT_SITE 302
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9R0E0"
FT VAR_SEQ 1..67
FT /note="Missing (in isoform d)"
FT /evidence="ECO:0000303|PubMed:17174523"
FT /id="VSP_045383"
FT VAR_SEQ 1..11
FT /note="MCKYGKSNLAA -> MEVAKAVATNLSTAANSTVLRT (in isoform
FT b)"
FT /evidence="ECO:0000303|PubMed:17174523"
FT /id="VSP_045384"
SQ SEQUENCE 459 AA; 51300 MW; 55E8F89E0441281D CRC64;
MCKYGKSNLA AVASSTSSII GAAAAAVAEA QPSASPSTSS SFLLLEVPFR HLLRLQPPPY
FIAGTRRMAA QLDVTTLIAI VGFVFVFCLY LIHIIALSYS KYRLHHKVKE DSSLPGVSII
KPIVGKDNNL YENIESFFTT QYHKYELLFC FNSSDDEAVE VVKCLMKKYP KVDAKLFFGG
ETVGLNPKIN NMMPAYRSAL YPLILVSDSG IFMRSDGVLD MATTMMSHEK MALVTQTPYC
KDREGFDAAF EQMYFGTSHG RIYLAGNCMD FVCSTGMSSM MKKEALDECG GISNFGGYLA
EDYFFGRELA NRGYKSAISS HPALQNSSSV SVSSFLDRIC RWVKLRIAML PHILLVEPLQ
DCFPSGLIMA FSLNHLVGLN IMPILILHTI YWFSMDYSLM NSMQNGKLSF SPLQFMLIWL
LRELTAPFVF IKALLQPTIQ WRNNVFHLAW GGQILPPKC
