ID   GBA1_BOVIN              Reviewed;         536 AA.
AC   Q2KHZ8;
DT   20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT   07-MAR-2006, sequence version 1.
DT   24-JAN-2024, entry version 98.
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=GBA1; Synonyms=GBA {ECO:0000250|UniProtKB:P04062};
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Heart ventricle;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (JAN-2006) 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:76302; 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       GBA1-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; BC112823; AAI12824.1; -; mRNA.
DR   RefSeq; NP_001039886.1; NM_001046421.2.
DR   AlphaFoldDB; Q2KHZ8; -.
DR   SMR; Q2KHZ8; -.
DR   STRING; 9913.ENSBTAP00000060772; -.
DR   BindingDB; Q2KHZ8; -.
DR   ChEMBL; CHEMBL1275219; -.
DR   CAZy; GH30; Glycoside Hydrolase Family 30.
DR   GlyCosmos; Q2KHZ8; 6 sites, No reported glycans.
DR   PaxDb; 9913-ENSBTAP00000019765; -.
DR   GeneID; 537087; -.
DR   KEGG; bta:537087; -.
DR   CTD; 2629; -.
DR   eggNOG; KOG2566; Eukaryota.
DR   InParanoid; Q2KHZ8; -.
DR   OrthoDB; 3473901at2759; -.
DR   UniPathway; UPA00296; -.
DR   PRO; PR:Q2KHZ8; -.
DR   Proteomes; UP000009136; Unplaced.
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   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; 2.
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_0000278648"
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        208
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|UniProtKB:P04062"
FT   DISULFID        57..62
FT                   /evidence="ECO:0000250|UniProtKB:P04062"
SQ   SEQUENCE   536 AA;  59855 MW;  1260A9C428E5D3FE CRC64;
     MELSSPSREE YPMPRGRVGI MAASLMGLLL LHTVSWVSGA RPCSPKSFGY SSVVCVCNGT
     YCDSLDPLTL PDPGTFSRFE STRSGRRMEL SLGTIQANRT GTGLLLTLQP DQKFQKVKGF
     GGAMTDAAAL NILALSPAAR NLLLKSYFSE EGIEYNIIRV PMASCDFSIR TYTYDDSPDD
     FQLLNFSLPE EDVKLKIPLI HQALELANRS VSLFASPWTS PTWLKTNGAV NGKGTLKGQA
     GDLYHKTWAR YFVKFLDAYA EHKLRFWAVT AENEPTAGLL TGYPFQCLGF TPEHQRDFIA
     RDLGPILANS THRDVRLLML DDQRLLLPRW AQVVLADPEA AKYVHGIAVH WYLDFLAPAK
     ATLGETHRLF PNTMLFASEA CVGSKFWEQS VRLGSWDRGM RYSHSIITNL LYHVVGWTDW
     NLALNPEGGP NWVRNFVDSP IIVDIAKDTF YKQPMFYHLG HFSKFIPEGS QRVGLVASKK
     SDLDTVALLR PDGSAVAVVL NRSSKDVPLT IKDPAVGFME TVSPGYSIHT YLWRRQ
//