GLCM_PONAB
ID GLCM_PONAB Reviewed; 536 AA.
AC Q5R8E3; Q5RBT6;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Lysosomal acid glucosylceramidase {ECO:0000305};
DE EC=3.2.1.45 {ECO:0000250|UniProtKB:P04062};
DE AltName: Full=Acid beta-glucosidase;
DE AltName: Full=Beta-glucocerebrosidase;
DE AltName: Full=Cholesterol glucosyltransferase {ECO:0000250|UniProtKB:P04062};
DE Short=SGTase {ECO:0000250|UniProtKB:P04062};
DE EC=2.4.1.- {ECO:0000250|UniProtKB:P04062};
DE AltName: Full=Cholesteryl-beta-glucosidase {ECO:0000250|UniProtKB:P04062};
DE EC=3.2.1.- {ECO:0000250|UniProtKB:P04062};
DE AltName: Full=D-glucosyl-N-acylsphingosine glucohydrolase;
DE AltName: Full=Lysosomal cholesterol glycosyltransferase {ECO:0000305};
DE AltName: Full=Lysosomal galactosylceramidase {ECO:0000305};
DE EC=3.2.1.46 {ECO:0000250|UniProtKB:P04062};
DE AltName: Full=Lysosomal glycosylceramidase {ECO:0000305};
DE Flags: Precursor;
GN Name=GBA {ECO:0000250|UniProtKB:P04062};
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Glucosylceramidase that catalyzes, within the lysosomal
CC compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta-
CC D-glucosyl-(1<->1')-N-acylsphing-4-enine) into free ceramides (such as
CC N-acylsphing-4-enine) and glucose. Plays a central role in the
CC degradation of complex lipids and the turnover of cellular membranes.
CC Through the production of ceramides, participates in the PKC-activated
CC salvage pathway of ceramide formation. Catalyzes the glucosylation of
CC cholesterol, through a transglucosylation reaction where glucose is
CC transferred from GlcCer to cholesterol. GlcCer containing mono-
CC unsaturated fatty acids (such as beta-D-glucosyl-N-(9Z-octadecenoyl)-
CC sphing-4-enine) are preferred as glucose donors for cholesterol
CC glucosylation when compared with GlcCer containing same chain length of
CC saturated fatty acids (such as beta-D-glucosyl-N-octadecanoyl-sphing-4-
CC enine). Under specific conditions, may alternatively catalyze the
CC reverse reaction, transferring glucose from cholesteryl 3-beta-D-
CC glucoside to ceramide. Can also hydrolyze cholesteryl 3-beta-D-
CC glucoside producing glucose and cholesterol. Catalyzes the hydrolysis
CC of galactosylceramides/GalCers (such as beta-D-galactosyl-(1<->1')-N-
CC acylsphing-4-enine), as well as the transfer of galactose between
CC GalCers and cholesterol in vitro, but with lower activity than with
CC GlcCers. Contrary to GlcCer and GalCer, xylosylceramide/XylCer (such as
CC beta-D-xyosyl-(1<->1')-N-acylsphing-4-enine) is not a good substrate
CC for hydrolysis, however it is a good xylose donor for transxylosylation
CC activity to form cholesteryl 3-beta-D-xyloside.
CC {ECO:0000250|UniProtKB:P04062}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine + H2O = an N-
CC acylsphing-4-enine + D-glucose; Xref=Rhea:RHEA:13269,
CC ChEBI:CHEBI:4167, ChEBI:CHEBI:15377, ChEBI:CHEBI:22801,
CC ChEBI:CHEBI:52639; EC=3.2.1.45;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13270;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine + H2O = an
CC N-acylsphing-4-enine + D-galactose; Xref=Rhea:RHEA:14297,
CC ChEBI:CHEBI:4139, ChEBI:CHEBI:15377, ChEBI:CHEBI:18390,
CC ChEBI:CHEBI:52639; EC=3.2.1.46;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14298;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesteryl 3-beta-D-glucoside + H2O = cholesterol + D-
CC glucose; Xref=Rhea:RHEA:11956, ChEBI:CHEBI:4167, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:17495;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11957;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine + cholesterol
CC = an N-acylsphing-4-enine + cholesteryl 3-beta-D-glucoside;
CC Xref=Rhea:RHEA:58264, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495,
CC ChEBI:CHEBI:22801, ChEBI:CHEBI:52639;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58265;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58266;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-N-(9Z-octadecenoyl)-sphing-4E-enine +
CC cholesterol = cholesteryl 3-beta-D-glucoside + N-(9Z-octadecenoyl)-
CC sphing-4-enine; Xref=Rhea:RHEA:58324, ChEBI:CHEBI:16113,
CC ChEBI:CHEBI:17495, ChEBI:CHEBI:77996, ChEBI:CHEBI:139140;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58325;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58326;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-N-octanoylsphing-4E-enine + cholesterol =
CC cholesteryl 3-beta-D-glucoside + N-octanoylsphing-4-enine;
CC Xref=Rhea:RHEA:70303, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495,
CC ChEBI:CHEBI:45815, ChEBI:CHEBI:65222;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70304;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70305;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-N-dodecanoylsphing-4-enine + cholesterol =
CC cholesteryl 3-beta-D-glucoside + N-dodecanoylsphing-4-enine;
CC Xref=Rhea:RHEA:70307, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495,
CC ChEBI:CHEBI:72956, ChEBI:CHEBI:76297;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70308;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70309;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-(1<->1)-N-octadecanoylsphing-4-enine +
CC cholesterol = cholesteryl 3-beta-D-glucoside + N-octadecanoylsphing-
CC 4-enine; Xref=Rhea:RHEA:70311, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495,
CC ChEBI:CHEBI:72961, ChEBI:CHEBI:84719;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70312;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70313;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-(1<->1')-N-(15Z-tetracosenoyl)-sphing-4-enine
CC + cholesterol = cholesteryl 3-beta-D-glucoside + N-(15Z-
CC tetracosenoyl)-sphing-4-enine; Xref=Rhea:RHEA:70315,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:17495, ChEBI:CHEBI:74450,
CC ChEBI:CHEBI:84746; Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70316;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70317;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine +
CC cholesterol = an N-acylsphing-4-enine + cholesteryl 3-beta-D-
CC galactoside; Xref=Rhea:RHEA:70235, ChEBI:CHEBI:16113,
CC ChEBI:CHEBI:18390, ChEBI:CHEBI:52639, ChEBI:CHEBI:189066;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70236;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70237;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(beta-D-galactosyl)-N-dodecanoylsphing-4-enine + cholesterol
CC = cholesteryl 3-beta-D-galactoside + N-dodecanoylsphing-4-enine;
CC Xref=Rhea:RHEA:70255, ChEBI:CHEBI:16113, ChEBI:CHEBI:72956,
CC ChEBI:CHEBI:73432, ChEBI:CHEBI:189066;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70256;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70257;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-xylosyl-(1<->1')-N-acylsphing-4-enine + cholesterol =
CC an N-acylsphing-4-enine + cholesteryl 3-beta-D-xyloside;
CC Xref=Rhea:RHEA:70239, ChEBI:CHEBI:16113, ChEBI:CHEBI:52639,
CC ChEBI:CHEBI:189067, ChEBI:CHEBI:189068;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70240;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-xylosyl-(1<->1')-N-(9Z-octadecenoyl)-sphing-4-enine +
CC cholesterol = cholesteryl 3-beta-D-xyloside + N-(9Z-octadecenoyl)-
CC sphing-4-enine; Xref=Rhea:RHEA:70251, ChEBI:CHEBI:16113,
CC ChEBI:CHEBI:77996, ChEBI:CHEBI:189067, ChEBI:CHEBI:189081;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70252;
CC Evidence={ECO:0000250|UniProtKB:P04062};
CC -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC {ECO:0000250|UniProtKB:P04062}.
CC -!- PATHWAY: Sphingolipid metabolism. {ECO:0000250|UniProtKB:P04062}.
CC -!- SUBUNIT: Interacts with saposin-C. Interacts with SCARB2. Interacts
CC with TCP1. Interacts with GRN; this interaction prevents aggregation of
CC GBA-SCARB2 complex via interaction with HSPA1A upon stress (By
CC similarity). {ECO:0000250|UniProtKB:P04062}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:P04062};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P04062}; Lumenal
CC side {ECO:0000250|UniProtKB:P04062}. Note=Interaction with saposin-C
CC promotes membrane association. Targeting to lysosomes occurs through an
CC alternative MPR-independent mechanism via SCARB2.
CC {ECO:0000250|UniProtKB:P04062}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 30 family. {ECO:0000305}.
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DR EMBL; CR858547; CAH90774.1; -; mRNA.
DR EMBL; CR859809; CAH91967.1; -; mRNA.
DR RefSeq; NP_001127488.1; NM_001134016.1.
DR RefSeq; NP_001128784.1; NM_001135312.1.
DR AlphaFoldDB; Q5R8E3; -.
DR SMR; Q5R8E3; -.
DR STRING; 9601.ENSPPYP00000000872; -.
DR CAZy; GH30; Glycoside Hydrolase Family 30.
DR Ensembl; ENSPPYT00000000903; ENSPPYP00000000872; ENSPPYG00000000751.
DR GeneID; 100174563; -.
DR GeneID; 100189687; -.
DR KEGG; pon:100174563; -.
DR CTD; 2629; -.
DR eggNOG; KOG2566; Eukaryota.
DR GeneTree; ENSGT00390000009464; -.
DR HOGENOM; CLU_014379_1_2_1; -.
DR InParanoid; Q5R8E3; -.
DR OrthoDB; 644299at2759; -.
DR UniPathway; UPA00296; -.
DR Proteomes; UP000001595; Chromosome 1.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0004336; F:galactosylceramidase activity; IEA:RHEA.
DR GO; GO:0004348; F:glucosylceramidase activity; ISS:UniProtKB.
DR GO; GO:0046527; F:glucosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0050295; F:steryl-beta-glucosidase activity; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; ISS:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; ISS:UniProtKB.
DR GO; GO:0006680; P:glucosylceramide catabolic process; ISS:UniProtKB.
DR GO; GO:0030259; P:lipid glycosylation; ISS:UniProtKB.
DR GO; GO:0007040; P:lysosome organization; ISS:UniProtKB.
DR GO; GO:0032006; P:regulation of TOR signaling; ISS:UniProtKB.
DR InterPro; IPR033452; GH30_C.
DR InterPro; IPR001139; Glyco_hydro_30.
DR InterPro; IPR033453; Glyco_hydro_30_TIM-barrel.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR PANTHER; PTHR11069; PTHR11069; 1.
DR Pfam; PF02055; Glyco_hydro_30; 1.
DR Pfam; PF17189; Glyco_hydro_30C; 1.
DR PRINTS; PR00843; GLHYDRLASE30.
DR SUPFAM; SSF51445; SSF51445; 1.
PE 2: Evidence at transcript level;
KW Cholesterol metabolism; Disulfide bond; Glycoprotein; Glycosidase;
KW Glycosyltransferase; Hydrolase; Lipid metabolism; Lysosome; Membrane;
KW Reference proteome; Signal; Sphingolipid metabolism; Steroid metabolism;
KW Sterol metabolism; Transferase.
FT SIGNAL 1..39
FT /evidence="ECO:0000250"
FT CHAIN 40..536
FT /note="Lysosomal acid glucosylceramidase"
FT /id="PRO_0000278649"
FT ACT_SITE 274
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT ACT_SITE 379
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 501
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 43..55
FT /evidence="ECO:0000250"
FT DISULFID 57..62
FT /evidence="ECO:0000250"
FT CONFLICT 61
FT /note="Y -> C (in Ref. 1; CAH90774)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="R -> H (in Ref. 1; CAH90774)"
FT /evidence="ECO:0000305"
FT CONFLICT 478
FT /note="S -> G (in Ref. 1; CAH90774)"
FT /evidence="ECO:0000305"
FT CONFLICT 534
FT /note="R -> C (in Ref. 1; CAH90774)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 536 AA; 59682 MW; E4D6A3B89FAFE8CF CRC64;
MEFSSPSREE CPKPSGRVNI MAGSLTGLLL LQAVSWASGA RPCIPKSFGY SSVVCVCNAT
YCDSLDPLTF PALGTFSRYE STRSGRRMEL STGTIQANHT GTGLLLTLQP EQKFQKVKGF
GGAMTDAAAL NILALSPPAQ NLLLKSYFSE EGIGYNIIRV PMASCDFSIR TYTYADTPDD
FQLHNFSLPE EDTKLKIPLI HRALQLARRP VSLLASPWTS PTWLKTNGAV NGKGSLKGQP
GDIYHQTWAR YFVKFLDAYA EHKLQFWAVT AENEPSAGLL SGYPFQCLGF TPEHQRDFIA
RDLGPTLANS THHNVRLLML DDQRLLLPHW AKVVLTDPEA AKYVHGIAVH WYLDFLAPAK
ATLGETHHLF PNTMLFASEA CVGSKFWEQS VRLGSWDRGM QYSHSIITNL LYHVVGWTDW
NLALNPEGGP NWVRNFVDSP IIVDITKDTF YKQPMFYHLG HFSKFIPEGS QRVGLVASQK
NDLDTVALMH PDGSAVVVVL NRSSKDVPLT IKDPAVGFLE TISPGYSIHT YLWRRQ
