ID   GBA1_MOUSE              Reviewed;         515 AA.
AC   P17439; Q78NR7;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   27-MAR-2024, entry version 186.
DE   RecName: Full=Lysosomal acid glucosylceramidase {ECO:0000305};
DE            Short=Lysosomal acid GCase {ECO:0000303|PubMed:24211208};
DE            EC=3.2.1.45 {ECO:0000269|PubMed:1594045, ECO:0000269|PubMed:24211208};
DE   AltName: Full=Acid beta-glucosidase;
DE   AltName: Full=Beta-glucocerebrosidase;
DE   AltName: Full=Cholesterol glucosyltransferase {ECO:0000305|PubMed:24211208};
DE            Short=SGTase {ECO:0000303|PubMed:24211208};
DE            EC=2.4.1.- {ECO:0000269|PubMed:24211208};
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:0000312|MGI:MGI:95665};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2740343; DOI=10.1073/pnas.86.13.5049;
RA   O'Neill R.R., Tokoru T., Kozak C.A., Brady R.O.;
RT   "Comparison of the chromosomal localization of murine and human
RT   glucocerebrosidase genes and of the deduced amino acid sequences.";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:5049-5053(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129/SvJ;
RA   Sinclair G., Wilson M.D., McKinnel L., Koop B.F., Choy F.Y.M.;
RT   "Comparative sequence analysis of the mouse and human GBA locus.";
RL   Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18.
RC   STRAIN=BALB/cJ;
RX   PubMed=1317175; DOI=10.1016/s0006-291x(05)80049-x;
RA   Carstea E.D., Murray G.J., O'Neill R.R.;
RT   "Molecular and functional characterization of the murine glucocerebrosidase
RT   gene.";
RL   Biochem. Biophys. Res. Commun. 184:1477-1483(1992).
RN   [6]
RP   PROTEIN SEQUENCE OF 210-217, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=OF1; TISSUE=Hippocampus;
RA   Lubec G., Sunyer B., Chen W.-Q.;
RL   Submitted (JAN-2009) to UniProtKB.
RN   [7]
RP   CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=1594045; DOI=10.1038/357407a0;
RA   Tybulewicz V.L., Tremblay M.L., LaMarca M.E., Willemsen R.,
RA   Stubblefield B.K., Winfield S., Zablocka B., Sidransky E., Martin B.M.,
RA   Huang S.P.;
RT   "Animal model of Gaucher's disease from targeted disruption of the mouse
RT   glucocerebrosidase gene.";
RL   Nature 357:407-410(1992).
RN   [8]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-165.
RC   TISSUE=Epidermis;
RX   PubMed=16170054; DOI=10.1074/mcp.m500203-mcp200;
RA   Uematsu R., Furukawa J., Nakagawa H., Shinohara Y., Deguchi K., Monde K.,
RA   Nishimura S.;
RT   "High throughput quantitative glycomics and glycoform-focused proteomics of
RT   murine dermis and epidermis.";
RL   Mol. Cell. Proteomics 4:1977-1989(2005).
RN   [9]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-289.
RX   PubMed=19349973; DOI=10.1038/nbt.1532;
RA   Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA   Schiess R., Aebersold R., Watts J.D.;
RT   "Mass-spectrometric identification and relative quantification of N-linked
RT   cell surface glycoproteins.";
RL   Nat. Biotechnol. 27:378-386(2009).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [11]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=22665763; DOI=10.1073/pnas.1200941109;
RA   Liu J., Halene S., Yang M., Iqbal J., Yang R., Mehal W.Z., Chuang W.L.,
RA   Jain D., Yuen T., Sun L., Zaidi M., Mistry P.K.;
RT   "Gaucher disease gene GBA functions in immune regulation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:10018-10023(2012).
RN   [12]
RP   FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND ACTIVITY REGULATION.
RX   PubMed=24211208; DOI=10.1016/j.bbrc.2013.10.145;
RA   Akiyama H., Kobayashi S., Hirabayashi Y., Murakami-Murofushi K.;
RT   "Cholesterol glucosylation is catalyzed by transglucosylation reaction of
RT   beta-glucosidase 1.";
RL   Biochem. Biophys. Res. Commun. 441:838-843(2013).
RN   [13]
RP   INTERACTION WITH GRN.
RX   PubMed=27789271; DOI=10.1016/j.ebiom.2016.10.010;
RA   Jian J., Tian Q.Y., Hettinghouse A., Zhao S., Liu H., Wei J., Grunig G.,
RA   Zhang W., Setchell K.D.R., Sun Y., Overkleeft H.S., Chan G.L., Liu C.J.;
RT   "Progranulin Recruits HSP70 to beta-Glucocerebrosidase and Is Therapeutic
RT   Against Gaucher Disease.";
RL   EBioMedicine 13:212-224(2016).
RN   [14]
RP   FUNCTION.
RX   PubMed=27378698; DOI=10.1093/hmg/ddw185;
RA   Magalhaes J., Gegg M.E., Migdalska-Richards A., Doherty M.K.,
RA   Whitfield P.D., Schapira A.H.;
RT   "Autophagic lysosome reformation dysfunction in glucocerebrosidase
RT   deficient cells: relevance to Parkinson disease.";
RL   Hum. Mol. Genet. 25:3432-3445(2016).
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 (PubMed:24211208). Plays a central
CC       role in the degradation of complex lipids and the turnover of cellular
CC       membranes (PubMed:27378698). Through the production of ceramides,
CC       participates in the PKC-activated salvage pathway of ceramide formation
CC       (By similarity). Catalyzes the glucosylation of cholesterol, through a
CC       transglucosylation reaction where glucose is transferred from GlcCer to
CC       cholesterol (PubMed:24211208). GlcCer containing mono-unsaturated fatty
CC       acids (such as beta-D-glucosyl-N-(9Z-octadecenoyl)-sphing-4-enine) are
CC       preferred as glucose donors for cholesterol glucosylation when compared
CC       with GlcCer containing same chain length of saturated fatty acids (such
CC       as beta-D-glucosyl-N-octadecanoyl-sphing-4-enine) (By similarity).
CC       Under specific conditions, may alternatively catalyze the reverse
CC       reaction, transferring glucose from cholesteryl 3-beta-D-glucoside to
CC       ceramide (By similarity). Can also hydrolyze cholesteryl 3-beta-D-
CC       glucoside producing glucose and cholesterol (By similarity). Catalyzes
CC       the hydrolysis of galactosylceramides/GalCers (such as beta-D-
CC       galactosyl-(1<->1')-N-acylsphing-4-enine), as well as the transfer of
CC       galactose between GalCers and cholesterol in vitro, but with lower
CC       activity than with GlcCers (By similarity). Contrary to GlcCer and
CC       GalCer, xylosylceramide/XylCer (such as beta-D-xyosyl-(1<->1')-N-
CC       acylsphing-4-enine) is not a good substrate for hydrolysis, however it
CC       is a good xylose donor for transxylosylation activity to form
CC       cholesteryl 3-beta-D-xyloside (By similarity).
CC       {ECO:0000250|UniProtKB:P04062, ECO:0000269|PubMed:24211208,
CC       ECO:0000269|PubMed:27378698}.
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:0000269|PubMed:24211208};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13270;
CC         Evidence={ECO:0000305|PubMed:24211208};
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:0000269|PubMed:24211208};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11957;
CC         Evidence={ECO:0000305|PubMed:24211208};
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:0000269|PubMed:24211208};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58265;
CC         Evidence={ECO:0000305|PubMed:24211208};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58266;
CC         Evidence={ECO:0000305};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=beta-D-glucosyl-(1<->1')-N-hexadecanoylsphing-4-enine +
CC         cholesterol = cholesteryl 3-beta-D-glucoside + N-hexadecanoylsphing-
CC         4-enine; Xref=Rhea:RHEA:58316, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495,
CC         ChEBI:CHEBI:72959, ChEBI:CHEBI:84716;
CC         Evidence={ECO:0000269|PubMed:24211208};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58317;
CC         Evidence={ECO:0000305|PubMed:24211208};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58318;
CC         Evidence={ECO:0000305};
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   -!- ACTIVITY REGULATION: Inhibited by conduritol B epoxide/CBE.
CC       {ECO:0000269|PubMed:24211208}.
CC   -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC       {ECO:0000269|PubMed:24211208}.
CC   -!- PATHWAY: Sphingolipid metabolism. {ECO:0000269|PubMed:24211208}.
CC   -!- SUBUNIT: Interacts with saposin-C. Interacts with SCARB2. Interacts
CC       with TCP1 (By similarity). Interacts with GRN; this interaction
CC       prevents aggregation of GBA1-SCARB2 complex via interaction with HSPA1A
CC       upon stress (PubMed:27789271). {ECO:0000250|UniProtKB:P04062,
CC       ECO:0000269|PubMed:27789271}.
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
CC       an alternative MPR-independent mechanism via SCARB2.
CC       {ECO:0000250|UniProtKB:P04062}.
CC   -!- DISRUPTION PHENOTYPE: Homozygous knockout mice die within 24 hours of
CC       birth (PubMed:1594045). They are under weight, respire abnormally and
CC       show rapidly progressing cyanosis (PubMed:1594045). Feeding and
CC       movement are also decreased in these mice (PubMed:1594045). Macrophages
CC       accumulating glucosylceramides in tubular lysosomal deposits are found
CC       in liver (in Kupffer cells), bone marrow, spleen and brain
CC       (PubMed:1594045). Hematopoietic stem cells conditional knockout of
CC       GBA1, leads to widespread and organ-specific dysfunction of immune
CC       cells. Thymus shows the earliest alteration with features of impaired
CC       T-cell maturation, aberrant B-cell recruitment, enhanced antigen
CC       presentation, and impaired egress of mature thymocytes
CC       (PubMed:22665763). {ECO:0000269|PubMed:1594045,
CC       ECO:0000269|PubMed:22665763}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 30 family. {ECO:0000305}.
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DR   EMBL; M24119; AAA37671.1; -; mRNA.
DR   EMBL; AY115108; AAM66757.1; -; Genomic_DNA.
DR   EMBL; AK082767; BAC38609.1; -; mRNA.
DR   EMBL; BC006663; AAH06663.1; -; mRNA.
DR   EMBL; M89949; AAA37665.1; -; Genomic_DNA.
DR   CCDS; CCDS17493.1; -.
DR   PIR; A32931; A32931.
DR   RefSeq; NP_001070879.1; NM_001077411.2.
DR   RefSeq; NP_032120.1; NM_008094.5.
DR   AlphaFoldDB; P17439; -.
DR   SMR; P17439; -.
DR   BioGRID; 199844; 11.
DR   IntAct; P17439; 3.
DR   STRING; 10090.ENSMUSP00000130660; -.
DR   BindingDB; P17439; -.
DR   ChEMBL; CHEMBL2278; -.
DR   SwissLipids; SLP:000001930; -.
DR   CAZy; GH30; Glycoside Hydrolase Family 30.
DR   GlyConnect; 2339; 3 N-Linked glycans (3 sites).
DR   GlyCosmos; P17439; 5 sites, 3 glycans.
DR   GlyGen; P17439; 5 sites, 3 N-linked glycans (3 sites).
DR   iPTMnet; P17439; -.
DR   PhosphoSitePlus; P17439; -.
DR   SwissPalm; P17439; -.
DR   EPD; P17439; -.
DR   jPOST; P17439; -.
DR   MaxQB; P17439; -.
DR   PaxDb; 10090-ENSMUSP00000130660; -.
DR   PeptideAtlas; P17439; -.
DR   ProteomicsDB; 268831; -.
DR   Pumba; P17439; -.
DR   Antibodypedia; 1678; 565 antibodies from 34 providers.
DR   DNASU; 14466; -.
DR   Ensembl; ENSMUST00000077367.11; ENSMUSP00000076589.5; ENSMUSG00000028048.12.
DR   Ensembl; ENSMUST00000167998.2; ENSMUSP00000130660.2; ENSMUSG00000028048.12.
DR   GeneID; 14466; -.
DR   KEGG; mmu:14466; -.
DR   UCSC; uc008pyb.2; mouse.
DR   AGR; MGI:95665; -.
DR   CTD; 2629; -.
DR   MGI; MGI:95665; Gba1.
DR   VEuPathDB; HostDB:ENSMUSG00000028048; -.
DR   eggNOG; KOG2566; Eukaryota.
DR   GeneTree; ENSGT00390000009464; -.
DR   HOGENOM; CLU_014379_1_2_1; -.
DR   InParanoid; P17439; -.
DR   OMA; FGGIAWH; -.
DR   OrthoDB; 3473901at2759; -.
DR   PhylomeDB; P17439; -.
DR   TreeFam; TF314254; -.
DR   BRENDA; 3.2.1.45; 3474.
DR   Reactome; R-MMU-9840310; Glycosphingolipid catabolism.
DR   UniPathway; UPA00296; -.
DR   BioGRID-ORCS; 14466; 6 hits in 80 CRISPR screens.
DR   ChiTaRS; Gba; mouse.
DR   PRO; PR:P17439; -.
DR   Proteomes; UP000000589; Chromosome 3.
DR   RNAct; P17439; Protein.
DR   Bgee; ENSMUSG00000028048; Expressed in esophagus and 289 other cell types or tissues.
DR   ExpressionAtlas; P17439; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IDA:MGI.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR   GO; GO:0043202; C:lysosomal lumen; IDA:BHF-UCL.
DR   GO; GO:0005765; C:lysosomal membrane; IDA:BHF-UCL.
DR   GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR   GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR   GO; GO:0008422; F:beta-glucosidase activity; IDA:MGI.
DR   GO; GO:0004336; F:galactosylceramidase activity; IEA:RHEA.
DR   GO; GO:0004348; F:glucosylceramidase activity; IDA:UniProtKB.
DR   GO; GO:0046527; F:glucosyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0016787; F:hydrolase activity; IDA:MGI.
DR   GO; GO:0005124; F:scavenger receptor binding; ISO:MGI.
DR   GO; GO:0005102; F:signaling receptor binding; IPI:BHF-UCL.
DR   GO; GO:0050295; F:steryl-beta-glucosidase activity; ISS:UniProtKB.
DR   GO; GO:0019882; P:antigen processing and presentation; IMP:MGI.
DR   GO; GO:1905037; P:autophagosome organization; IMP:ARUK-UCL.
DR   GO; GO:0006914; P:autophagy; IMP:UniProtKB.
DR   GO; GO:1901805; P:beta-glucoside catabolic process; ISO:MGI.
DR   GO; GO:0048854; P:brain morphogenesis; IMP:MGI.
DR   GO; GO:0048469; P:cell maturation; IMP:MGI.
DR   GO; GO:0009267; P:cellular response to starvation; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:MGI.
DR   GO; GO:0007417; P:central nervous system development; IMP:MGI.
DR   GO; GO:0046513; P:ceramide biosynthetic process; ISO:MGI.
DR   GO; GO:0021694; P:cerebellar Purkinje cell layer formation; IMP:MGI.
DR   GO; GO:0008203; P:cholesterol metabolic process; IDA:UniProtKB.
DR   GO; GO:0008340; P:determination of adult lifespan; IMP:MGI.
DR   GO; GO:0061436; P:establishment of skin barrier; ISO:MGI.
DR   GO; GO:0006680; P:glucosylceramide catabolic process; IDA:UniProtKB.
DR   GO; GO:0006678; P:glucosylceramide metabolic process; IMP:MGI.
DR   GO; GO:0071425; P:hematopoietic stem cell proliferation; IMP:MGI.
DR   GO; GO:0048872; P:homeostasis of number of cells; IMP:MGI.
DR   GO; GO:0030259; P:lipid glycosylation; IDA:UniProtKB.
DR   GO; GO:0019915; P:lipid storage; IMP:MGI.
DR   GO; GO:0072676; P:lymphocyte migration; IMP:MGI.
DR   GO; GO:0007040; P:lysosome organization; IMP:UniProtKB.
DR   GO; GO:0014004; P:microglia differentiation; IMP:MGI.
DR   GO; GO:0061518; P:microglial cell proliferation; IMP:MGI.
DR   GO; GO:0007005; P:mitochondrion organization; IMP:MGI.
DR   GO; GO:0000423; P:mitophagy; IMP:MGI.
DR   GO; GO:0061744; P:motor behavior; IMP:MGI.
DR   GO; GO:0032715; P:negative regulation of interleukin-6 production; ISO:MGI.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR   GO; GO:0051248; P:negative regulation of protein metabolic process; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0050877; P:nervous system process; IMP:MGI.
DR   GO; GO:0050905; P:neuromuscular process; IMP:MGI.
DR   GO; GO:0051402; P:neuron apoptotic process; IMP:MGI.
DR   GO; GO:1904925; P:positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization; IMP:ARUK-UCL.
DR   GO; GO:1904457; P:positive regulation of neuronal action potential; ISO:MGI.
DR   GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0035307; P:positive regulation of protein dephosphorylation; ISO:MGI.
DR   GO; GO:1903061; P:positive regulation of protein lipidation; ISO:MGI.
DR   GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; ISO:MGI.
DR   GO; GO:1903052; P:positive regulation of proteolysis involved in protein catabolic process; IMP:ARUK-UCL.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:MGI.
DR   GO; GO:0021859; P:pyramidal neuron differentiation; IMP:MGI.
DR   GO; GO:0042391; P:regulation of membrane potential; IMP:MGI.
DR   GO; GO:0051246; P:regulation of protein metabolic process; IMP:ARUK-UCL.
DR   GO; GO:0032006; P:regulation of TOR signaling; IMP:UniProtKB.
DR   GO; GO:0022904; P:respiratory electron transport chain; IMP:MGI.
DR   GO; GO:0071548; P:response to dexamethasone; ISO:MGI.
DR   GO; GO:0043627; P:response to estrogen; ISO:MGI.
DR   GO; GO:0009268; P:response to pH; ISO:MGI.
DR   GO; GO:0033574; P:response to testosterone; ISO:MGI.
DR   GO; GO:0097066; P:response to thyroid hormone; ISO:MGI.
DR   GO; GO:0098773; P:skin epidermis development; ISO:MGI.
DR   GO; GO:0046512; P:sphingosine biosynthetic process; ISO:MGI.
DR   GO; GO:0033077; P:T cell differentiation in thymus; IMP:MGI.
DR   GO; GO:0023021; P:termination of signal transduction; ISO:MGI.
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.
DR   Genevisible; P17439; MM.
PE   1: Evidence at protein level;
KW   Cholesterol metabolism; Direct protein sequencing; Disulfide bond;
KW   Glycoprotein; Glycosidase; Glycosyltransferase; Hydrolase;
KW   Lipid metabolism; Lysosome; Membrane; Reference proteome; Signal;
KW   Sphingolipid metabolism; Steroid metabolism; Sterol metabolism;
KW   Transferase.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000250"
FT   CHAIN           20..515
FT                   /note="Lysosomal acid glucosylceramidase"
FT                   /id="PRO_0000012178"
FT   ACT_SITE        254
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        358
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        38
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        78
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        165
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16170054"
FT   CARBOHYD        289
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19349973"
FT   CARBOHYD        480
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        23..35
FT                   /evidence="ECO:0000250|UniProtKB:P04062"
FT   DISULFID        37..42
FT                   /evidence="ECO:0000250|UniProtKB:P04062"
SQ   SEQUENCE   515 AA;  57622 MW;  7CCD9176085FE2CB CRC64;
     MAARLIGFFL FQAVSWAYGA QPCIPKSFGY SSVVCVCNAS YCDSLDPVTL PALGTFSRYE
     STRRGRRMEL SVGAIQANRT GTGLLLTLQP EKKFQKVKGF GGAMTDATAL NILALSPPTQ
     KLLLRSYFST NGIEYNIIRV PMASCDFSIR VYTYADTPND FQLSNFSLPE EDTKLKIPLI
     HQALKMSSRP ISLFASPWTS PTWLKTNGRV NGKGSLKGQP GDIFHQTWAN YFVKFLDAYA
     KYGLRFWAVT AENEPTAGLF TGYPFQCLGF TPEHQRDFIS RDLGPALANS SHDVKLLMLD
     DQRLLLPRWA EVVLSDPEAA KYVHGIAVHW YMDFLAPAKA TLGETHRLFP NTMLFASEAC
     VGSKFWEQSV RLGSWDRGMQ YSHSIITNLL YHVTGWTDWN LALNPEGGPN WVRNFVDSPI
     IVDIPKDAFY KQPMFYHLGH FSKFIPEGSQ RVALVASEST DLETVALLRP DGSAVVVVLN
     RSSEDVPLTI SDPDLGFLET VSPGYSIHTY LWRRQ
//