ID   B7Z731_HUMAN            Unreviewed;       423 AA.
AC   B7Z731;
DT   03-MAR-2009, integrated into UniProtKB/TrEMBL.
DT   03-MAR-2009, sequence version 1.
DT   27-MAR-2024, entry version 66.
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:BAH13467.1};
RN   [1] {ECO:0000313|EMBL:BAH13467.1}
RP   NUCLEOTIDE SEQUENCE.
RC   TISSUE=Synovial membrane tissue {ECO:0000313|EMBL:BAH13467.1};
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; AK301374; BAH13467.1; -; mRNA.
DR   AlphaFoldDB; B7Z731; -.
DR   Allergome; 8244; Hom s Glucocerebrosidase.
DR   MaxQB; B7Z731; -.
DR   PeptideAtlas; B7Z731; -.
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:0016757; F:glycosyltransferase activity; IEA:UniProtKB-KW.
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; 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; GLUCOSYLCERAMIDASE; 1.
DR   PANTHER; PTHR11069:SF23; LYSOSOMAL ACID GLUCOSYLCERAMIDASE; 1.
DR   Pfam; PF02055; Glyco_hydro_30; 1.
DR   Pfam; PF17189; Glyco_hydro_30C; 1.
DR   PRINTS; PR00843; GLHYDRLASE30.
DR   SUPFAM; SSF51445; (Trans)glycosidases; 1.
DR   SUPFAM; SSF51011; Glycosyl hydrolase domain; 1.
PE   2: Evidence at transcript level;
KW   Glycosidase {ECO:0000256|RuleBase:RU361188};
KW   Glycosyltransferase {ECO:0000256|ARBA:ARBA00022676};
KW   Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|RuleBase:RU361188};
KW   Lipid metabolism {ECO:0000256|RuleBase:RU361188};
KW   Signal {ECO:0000256|ARBA:ARBA00022729};
KW   Sphingolipid metabolism {ECO:0000256|ARBA:ARBA00022919,
KW   ECO:0000256|RuleBase:RU361188};
KW   Transferase {ECO:0000256|ARBA:ARBA00022676}.
FT   DOMAIN          26..353
FT                   /note="Glycosyl hydrolase family 30 TIM-barrel"
FT                   /evidence="ECO:0000259|Pfam:PF02055"
FT   DOMAIN          356..418
FT                   /note="Glycosyl hydrolase family 30 beta sandwich"
FT                   /evidence="ECO:0000259|Pfam:PF17189"
SQ   SEQUENCE   423 AA;  47535 MW;  A4B5D6AAB39D04CC CRC64;
     MEFSSPSREE CPKPLSRVSV MAGSLTGLLL LQAVSWASGI GYNIIRVPMA SCDFSIRTYT
     YADTPDDFQL HNFSLPEEDT KLKIPLIHRA LQLALRPVSL LASPWTSPTW LKTNGAVNGK
     GSLKGQPGDI YHQTWARYFV KFLDAYAEHK LQFWAVTAEN EPSAGLLSGY PFQCLGFTPE
     HQRDFIARDL GPTLANSTHH NVRLLMLDDQ RLLLPHWAKV VLTDPEAAKY VHGIAVHWYL
     DFLAPAKATL GETHRLFPNT MLFASEACVG SKFWEQSVRL GSWDRGMQYS HSIITNLLYH
     VVGWTDWNLA LNPEGGPNWV RNFVDSPIIV DITKDTFYKQ PMFYHLGHFS KFIPEGSQRV
     GLVASQKNDL DAVALMHPDG SAVVVVLNRS SKDVPLTIKD PAVGFLETIS PGYSIHTYLW
     RRQ
//