ID   B4DHT6_HUMAN            Unreviewed;       341 AA.
AC   B4DHT6;
DT   23-SEP-2008, integrated into UniProtKB/TrEMBL.
DT   23-SEP-2008, sequence version 1.
DT   27-MAR-2024, entry version 67.
DE   RecName: Full=Glucosylceramidase {ECO:0000256|RuleBase:RU361188};
DE            EC=3.2.1.45 {ECO:0000256|RuleBase:RU361188};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606 {ECO:0000313|EMBL:BAG58248.1};
RN   [1] {ECO:0000313|EMBL:BAG58248.1}
RP   NUCLEOTIDE SEQUENCE.
RC   TISSUE=Caudate nucleus {ECO:0000313|EMBL:BAG58248.1};
RA   Wakamatsu A., Yamamoto J., Kimura K., Ishii S., Watanabe K., Sugiyama A.,
RA   Murakawa K., Kaida T., Tsuchiya K., Fukuzumi Y., Kumagai A., Oishi Y.,
RA   Yamamoto S., Ono Y., Komori Y., Yamazaki M., Kisu Y., Nishikawa T.,
RA   Sugano S., Nomura N., Isogai T.;
RT   "NEDO human cDNA sequencing project focused on splicing variants.";
RL   Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases.
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:0000256|ARBA:ARBA00033703};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70256;
CC         Evidence={ECO:0000256|ARBA:ARBA00033703};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70257;
CC         Evidence={ECO:0000256|ARBA:ARBA00033703};
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:0000256|ARBA:ARBA00033698};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14298;
CC         Evidence={ECO:0000256|ARBA:ARBA00033698};
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:0000256|ARBA:ARBA00033611};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70236;
CC         Evidence={ECO:0000256|ARBA:ARBA00033611};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70237;
CC         Evidence={ECO:0000256|ARBA:ARBA00033611};
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:0000256|ARBA:ARBA00001013};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13270;
CC         Evidence={ECO:0000256|ARBA:ARBA00001013};
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:0000256|ARBA:ARBA00033647};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58265;
CC         Evidence={ECO:0000256|ARBA:ARBA00033647};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58266;
CC         Evidence={ECO:0000256|ARBA:ARBA00033647};
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:0000256|ARBA:ARBA00033608};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70240;
CC         Evidence={ECO:0000256|ARBA:ARBA00033608};
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:76302; Evidence={ECO:0000256|ARBA:ARBA00035592};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70316;
CC         Evidence={ECO:0000256|ARBA:ARBA00035592};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70317;
CC         Evidence={ECO:0000256|ARBA:ARBA00035592};
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:0000256|ARBA:ARBA00033636};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70312;
CC         Evidence={ECO:0000256|ARBA:ARBA00033636};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70313;
CC         Evidence={ECO:0000256|ARBA:ARBA00033636};
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:0000256|ARBA:ARBA00033685};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58325;
CC         Evidence={ECO:0000256|ARBA:ARBA00033685};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58326;
CC         Evidence={ECO:0000256|ARBA:ARBA00033685};
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:0000256|ARBA:ARBA00033694};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70308;
CC         Evidence={ECO:0000256|ARBA:ARBA00033694};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70309;
CC         Evidence={ECO:0000256|ARBA:ARBA00033694};
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:0000256|ARBA:ARBA00033641};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70304;
CC         Evidence={ECO:0000256|ARBA:ARBA00033641};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70305;
CC         Evidence={ECO:0000256|ARBA:ARBA00033641};
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:0000256|ARBA:ARBA00033633};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70252;
CC         Evidence={ECO:0000256|ARBA:ARBA00033633};
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:0000256|ARBA:ARBA00033646};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11957;
CC         Evidence={ECO:0000256|ARBA:ARBA00033646};
CC   -!- PATHWAY: Sphingolipid metabolism. {ECO:0000256|ARBA:ARBA00004991}.
CC   -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC       {ECO:0000256|ARBA:ARBA00004731}.
CC   -!- SUBCELLULAR LOCATION: Lysosome membrane
CC       {ECO:0000256|ARBA:ARBA00004207}; Peripheral membrane protein
CC       {ECO:0000256|ARBA:ARBA00004207}; Lumenal side
CC       {ECO:0000256|ARBA:ARBA00004207}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 30 family.
CC       {ECO:0000256|ARBA:ARBA00005382, ECO:0000256|RuleBase:RU361188}.
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DR   EMBL; AK295259; BAG58248.1; -; mRNA.
DR   AlphaFoldDB; B4DHT6; -.
DR   Allergome; 8244; Hom s Glucocerebrosidase.
DR   PeptideAtlas; B4DHT6; -.
DR   PhylomeDB; B4DHT6; -.
DR   UniPathway; UPA00296; -.
DR   GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004336; F:galactosylceramidase activity; IEA:RHEA.
DR   GO; GO:0004348; F:glucosylceramidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0050295; F:steryl-beta-glucosidase activity; IEA:RHEA.
DR   GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0006665; P:sphingolipid metabolic process; IEA:UniProtKB-KW.
DR   Gene3D; 3.20.20.80; Glycosidases; 1.
DR   InterPro; IPR001139; Glyco_hydro_30.
DR   InterPro; IPR033453; Glyco_hydro_30_TIM-barrel.
DR   InterPro; IPR017853; Glycoside_hydrolase_SF.
DR   PANTHER; PTHR11069; GLUCOSYLCERAMIDASE; 1.
DR   PANTHER; PTHR11069:SF34; GLUCOSYLCERAMIDASE; 1.
DR   Pfam; PF02055; Glyco_hydro_30; 1.
DR   PRINTS; PR00843; GLHYDRLASE30.
DR   SUPFAM; SSF51445; (Trans)glycosidases; 1.
PE   2: Evidence at transcript level;
KW   Glycosidase {ECO:0000256|RuleBase:RU361188};
KW   Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|RuleBase:RU361188};
KW   Lipid metabolism {ECO:0000256|RuleBase:RU361188};
KW   Signal {ECO:0000256|ARBA:ARBA00022729, ECO:0000256|SAM:SignalP};
KW   Sphingolipid metabolism {ECO:0000256|RuleBase:RU361188}.
FT   SIGNAL          1..37
FT                   /evidence="ECO:0000256|SAM:SignalP"
FT   CHAIN           38..341
FT                   /note="Glucosylceramidase"
FT                   /evidence="ECO:0000256|SAM:SignalP"
FT                   /id="PRO_5002800808"
FT   DOMAIN          65..338
FT                   /note="Glycosyl hydrolase family 30 TIM-barrel"
FT                   /evidence="ECO:0000259|Pfam:PF02055"
SQ   SEQUENCE   341 AA;  38476 MW;  EB9B41EAABC5141A CRC64;
     MEFSSPSREE CPKPSGRVSI MAGSLTGLLL LQAVSWASDE CLQPLQEQKQ WALDGAEYRT
     IQANCTGTGI GYNIIWVPMA SCDFSIRTYT YADTPDDFQL HNFSLPEEDT KLKIPLIHRA
     LQLAQRPVSL LASPWTSPTR LKTKGAGNGK GPLKGQPRDI YHQTWARYIV KFLDAYAEHK
     LQFWAVTAEN EPSAGLLSGY PFQCLGFTPE HQRDFIARDL GPTLANGTHH NVRLLMLDDQ
     RLLLPHWAKV VLTDPEAAKY VHGIAVHWYL DFLAPAKATL RETHHLFPNT MLFASEACVG
     SKFWEQSVRL GSWDRGMQYS HSIITNLLYH VVGWTDWNPS L
//