GBA2_MOUSE
ID GBA2_MOUSE Reviewed; 918 AA.
AC Q69ZF3; Q6PGM3; Q8BTN9;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Non-lysosomal glucosylceramidase {ECO:0000305};
DE Short=NLGase {ECO:0000303|PubMed:23250757};
DE EC=3.2.1.45 {ECO:0000269|PubMed:17080196};
DE AltName: Full=Beta-glucocerebrosidase 2;
DE Short=Beta-glucosidase 2;
DE AltName: Full=Bile acid beta-glucosidase GBA2 {ECO:0000305|PubMed:17080196};
DE AltName: Full=Bile acid glucosyl transferase GBA2 {ECO:0000250|UniProtKB:Q9HCG7};
DE AltName: Full=Cholesterol glucosyltransferase GBA2 {ECO:0000305|PubMed:26724485};
DE EC=2.4.1.- {ECO:0000269|PubMed:26724485};
DE AltName: Full=Cholesteryl-beta-glucosidase GBA2 {ECO:0000305|PubMed:26724485};
DE EC=3.2.1.- {ECO:0000269|PubMed:26724485};
DE AltName: Full=Glucosylceramidase 2;
DE AltName: Full=Non-lysosomal cholesterol glycosyltransferase {ECO:0000305};
DE AltName: Full=Non-lysosomal galactosylceramidase {ECO:0000305};
DE EC=3.2.1.46 {ECO:0000269|PubMed:32144204};
DE AltName: Full=Non-lysosomal glycosylceramidase {ECO:0000305};
GN Name=Gba2 {ECO:0000312|MGI:MGI:2654325};
GN Synonyms=Kiaa1605 {ECO:0000312|EMBL:BAD32491.1};
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 [LARGE SCALE MRNA].
RC TISSUE=Thymus;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=17080196; DOI=10.1172/jci29224;
RA Yildiz Y., Matern H., Thompson B., Allegood J.C., Warren R.L.,
RA Ramirez D.M.O., Hammer R.E., Hamra F.K., Matern S., Russell D.W.;
RT "Mutation of beta-glucosidase 2 causes glycolipid storage disease and
RT impaired male fertility.";
RL J. Clin. Invest. 116:2985-2994(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-893, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, 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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23250757; DOI=10.1074/jbc.m112.414714;
RA Korschen H.G., Yildiz Y., Raju D.N., Schonauer S., Bonigk W., Jansen V.,
RA Kremmer E., Kaupp U.B., Wachten D.;
RT "The non-lysosomal beta-glucosidase GBA2 is a non-integral membrane-
RT associated protein at the endoplasmic reticulum (ER) and Golgi.";
RL J. Biol. Chem. 288:3381-3393(2013).
RN [8]
RP FUNCTION.
RX PubMed=25803043; DOI=10.1371/journal.pgen.1005063;
RA Raju D., Schonauer S., Hamzeh H., Flynn K.C., Bradke F., Vom Dorp K.,
RA Doermann P., Yildiz Y., Troetschel C., Poetsch A., Breiden B., Sandhoff K.,
RA Koerschen H.G., Wachten D.;
RT "Accumulation of glucosylceramide in the absence of the beta-glucosidase
RT GBA2 alters cytoskeletal dynamics.";
RL PLoS Genet. 11:E1005063-E1005063(2015).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND PATHWAY.
RX PubMed=26724485; DOI=10.1194/jlr.m064923;
RA Marques A.R., Mirzaian M., Akiyama H., Wisse P., Ferraz M.J., Gaspar P.,
RA Ghauharali-van der Vlugt K., Meijer R., Giraldo P., Alfonso P., Irun P.,
RA Dahl M., Karlsson S., Pavlova E.V., Cox T.M., Scheij S., Verhoek M.,
RA Ottenhoff R., van Roomen C.P., Pannu N.S., van Eijk M., Dekker N.,
RA Boot R.G., Overkleeft H.S., Blommaart E., Hirabayashi Y., Aerts J.M.;
RT "Glucosylated cholesterol in mammalian cells and tissues: formation and
RT degradation by multiple cellular beta-glucosidases.";
RL J. Lipid Res. 57:451-463(2016).
RN [10]
RP ACTIVITY REGULATION.
RX PubMed=28258214; DOI=10.1074/jbc.m116.762831;
RA Schonauer S., Koerschen H.G., Penno A., Rennhack A., Breiden B.,
RA Sandhoff K., Gutbrod K., Doermann P., Raju D.N., Haberkant P., Gerl M.J.,
RA Bruegger B., Zigdon H., Vardi A., Futerman A.H., Thiele C., Wachten D.;
RT "Identification of a feedback loop involving beta-glucosidase 2 and its
RT product sphingosine sheds light on the molecular mechanisms in Gaucher
RT disease.";
RL J. Biol. Chem. 292:6177-6189(2017).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=32144204; DOI=10.1074/jbc.ra119.012502;
RA Akiyama H., Ide M., Nagatsuka Y., Sayano T., Nakanishi E., Uemura N.,
RA Yuyama K., Yamaguchi Y., Kamiguchi H., Takahashi R., Aerts J.M.F.G.,
RA Greimel P., Hirabayashi Y.;
RT "Glucocerebrosidases catalyze a transgalactosylation reaction that yields a
RT newly-identified brain sterol metabolite, galactosylated cholesterol.";
RL J. Biol. Chem. 295:5257-5277(2020).
CC -!- FUNCTION: Non-lysosomal glucosylceramidase that catalyzes the
CC hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-
CC (1<->1')-N-acylsphing-4-enine) to free glucose and ceramides (such as
CC N-acylsphing-4-enine) (PubMed:17080196, PubMed:23250757). GlcCers are
CC membrane glycosphingolipids that have a wide intracellular distribution
CC (PubMed:23250757). They are the main precursors of more complex
CC glycosphingolipids that play a role in cellular growth,
CC differentiation, adhesion, signaling, cytoskeletal dynamics and
CC membrane properties (PubMed:25803043). Also involved in the
CC transglucosylation of cholesterol, transferring glucose from GlcCer,
CC thereby modifying its water solubility and biological properties
CC (PubMed:26724485, PubMed:32144204). Under specific conditions, may
CC catalyze the reverse reaction, transferring glucose from cholesteryl-3-
CC beta-D-glucoside to ceramide (such as N-acylsphing-4-enine)
CC (PubMed:26724485, PubMed:32144204). May play a role in the metabolism
CC of bile acids (PubMed:17080196). Able to hydrolyze bile acid 3-O-
CC glucosides as well as to produce bile acid-glucose conjugates thanks to
CC a bile acid glucosyl transferase activity (PubMed:17080196). Catalyzes
CC the hydrolysis of galactosylceramides/GalCers (such as beta-D-
CC galactosyl-(1<->1')-N-acylsphing-4-enine), as well as galactosyl
CC transfer between GalCers and cholesterol in vitro with lower activity
CC compared with their activity against GlcCers (PubMed:32144204).
CC {ECO:0000269|PubMed:17080196, ECO:0000269|PubMed:23250757,
CC ECO:0000269|PubMed:25803043, ECO:0000269|PubMed:26724485,
CC ECO:0000269|PubMed:32144204, ECO:0000303|PubMed:23250757}.
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:17080196, ECO:0000269|PubMed:23250757};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13270;
CC Evidence={ECO:0000269|PubMed:17080196};
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:0000269|PubMed:32144204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14298;
CC Evidence={ECO:0000269|PubMed:32144204};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-(1->3)-O-lithocholate + H2O = D-glucose +
CC lithocholate; Xref=Rhea:RHEA:58344, ChEBI:CHEBI:4167,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:29744, ChEBI:CHEBI:142611;
CC Evidence={ECO:0000269|PubMed:17080196};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58345;
CC Evidence={ECO:0000305|PubMed:17080196};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-(1->3)-O-chenodeoxycholate + H2O =
CC chenodeoxycholate + D-glucose; Xref=Rhea:RHEA:58340,
CC ChEBI:CHEBI:4167, ChEBI:CHEBI:15377, ChEBI:CHEBI:36234,
CC ChEBI:CHEBI:142610; Evidence={ECO:0000250|UniProtKB:Q9HCG7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58341;
CC Evidence={ECO:0000250|UniProtKB:Q9HCG7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a dolichyl beta-D-glucosyl phosphate + chenodeoxycholate = a
CC dolichyl phosphate + beta-D-glucosyl-(1->3)-O-chenodeoxycholate +
CC H(+); Xref=Rhea:RHEA:59104, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9528,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36234, ChEBI:CHEBI:57525,
CC ChEBI:CHEBI:57683, ChEBI:CHEBI:142610;
CC Evidence={ECO:0000250|UniProtKB:Q9HCG7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59105;
CC Evidence={ECO:0000250|UniProtKB:Q9HCG7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + octyl beta-D-glucose = beta-D-glucosyl-
CC (1->3)-O-chenodeoxycholate + octan-1-ol; Xref=Rhea:RHEA:59108,
CC ChEBI:CHEBI:16188, ChEBI:CHEBI:36234, ChEBI:CHEBI:41128,
CC ChEBI:CHEBI:142610; Evidence={ECO:0000250|UniProtKB:Q9HCG7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59109;
CC Evidence={ECO:0000250|UniProtKB:Q9HCG7};
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:26724485, ECO:0000269|PubMed:32144204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11957;
CC Evidence={ECO:0000269|PubMed:26724485, ECO:0000269|PubMed:32144204};
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:26724485, ECO:0000305|PubMed:32144204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58265;
CC Evidence={ECO:0000269|PubMed:26724485, ECO:0000305|PubMed:32144204};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58266;
CC Evidence={ECO:0000269|PubMed:26724485, ECO:0000305|PubMed:32144204};
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:0000305|PubMed:32144204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58325;
CC Evidence={ECO:0000305|PubMed:32144204};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58326;
CC Evidence={ECO:0000305|PubMed:32144204};
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:0000305|PubMed:32144204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70236;
CC Evidence={ECO:0000305|PubMed:32144204};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70237;
CC Evidence={ECO:0000305|PubMed:32144204};
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:Q9HCG7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70256;
CC Evidence={ECO:0000250|UniProtKB:Q9HCG7};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70257;
CC Evidence={ECO:0000250|UniProtKB:Q9HCG7};
CC -!- ACTIVITY REGULATION: Enzymatic activity is dependent on membrane
CC association and requires the presence of lipids (PubMed:23250757).
CC Inhibited by N-(adamantanemethyloxypentyl)-deoxynojirimycin/AMP-DNM
CC (PubMed:26724485). Inhibited by its product sphingosine/N-acylsphing-4-
CC enine in a feedback loop (PubMed:28258214). Also inhibited by other
CC non-acetylated sphingoid bases and their derivatives but not by
CC sphingosine-1-phosphate and complex sphingolipids (PubMed:28258214).
CC {ECO:0000269|PubMed:23250757, ECO:0000269|PubMed:26724485,
CC ECO:0000269|PubMed:28258214}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is between 6.0 and 7.0. {ECO:0000269|PubMed:26724485};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:17080196, ECO:0000269|PubMed:23250757,
CC ECO:0000269|PubMed:26724485, ECO:0000305|PubMed:32144204}.
CC -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC {ECO:0000269|PubMed:26724485, ECO:0000305|PubMed:32144204}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:23250757}; Peripheral membrane protein
CC {ECO:0000269|PubMed:23250757}; Cytoplasmic side
CC {ECO:0000269|PubMed:23250757}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:23250757}; Peripheral membrane protein
CC {ECO:0000269|PubMed:23250757}; Cytoplasmic side
CC {ECO:0000269|PubMed:23250757}. Note=Localization to the plasma membrane
CC and alternative topologies have also been reported.
CC {ECO:0000250|UniProtKB:Q9HCG7}.
CC -!- TISSUE SPECIFICITY: Widely expressed at low level (PubMed:17080196).
CC Highly expressed in testis and brain (PubMed:17080196). Ubiquitously
CC expressed in the brain (at protein level) (PubMed:23250757). Expressed
CC by Sertoli cells (at protein level) (PubMed:17080196).
CC {ECO:0000269|PubMed:17080196, ECO:0000269|PubMed:23250757}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout mice display an accumulation
CC of glucosylceramides in testis, brain and liver (PubMed:17080196). The
CC accumulation of glucosylceramides in Sertoli cells alters sperm shape
CC and males exhibit impaired fertility (PubMed:17080196). Despite the
CC bile acid glucosidase and transferase activities measured in vitro,
CC bile acid metabolism is normal in knockout mice (PubMed:17080196). No
CC obvious neurological symptoms, organomegaly or lifespan alteration are
CC observed (PubMed:17080196). Cholesterol metabolism and protein
CC glycosylation are also normal in these mice (PubMed:17080196).
CC {ECO:0000269|PubMed:17080196}.
CC -!- SIMILARITY: Belongs to the non-lysosomal glucosylceramidase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD32491.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK173213; BAD32491.1; ALT_INIT; mRNA.
DR EMBL; AK089192; BAC40785.1; -; mRNA.
DR EMBL; AL732626; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC056935; AAH56935.1; -; mRNA.
DR CCDS; CCDS18103.1; -.
DR RefSeq; NP_766280.2; NM_172692.3.
DR AlphaFoldDB; Q69ZF3; -.
DR SMR; Q69ZF3; -.
DR BioGRID; 230933; 1.
DR STRING; 10090.ENSMUSP00000030189; -.
DR BindingDB; Q69ZF3; -.
DR ChEMBL; CHEMBL5614; -.
DR DrugCentral; Q69ZF3; -.
DR SwissLipids; SLP:000001383; -.
DR CAZy; GH116; Glycoside Hydrolase Family 116.
DR iPTMnet; Q69ZF3; -.
DR PhosphoSitePlus; Q69ZF3; -.
DR SwissPalm; Q69ZF3; -.
DR EPD; Q69ZF3; -.
DR jPOST; Q69ZF3; -.
DR MaxQB; Q69ZF3; -.
DR PaxDb; Q69ZF3; -.
DR PeptideAtlas; Q69ZF3; -.
DR PRIDE; Q69ZF3; -.
DR ProteomicsDB; 273415; -.
DR Antibodypedia; 11711; 111 antibodies from 18 providers.
DR DNASU; 230101; -.
DR Ensembl; ENSMUST00000030189; ENSMUSP00000030189; ENSMUSG00000028467.
DR GeneID; 230101; -.
DR KEGG; mmu:230101; -.
DR UCSC; uc008sqi.2; mouse.
DR CTD; 57704; -.
DR MGI; MGI:2654325; Gba2.
DR VEuPathDB; HostDB:ENSMUSG00000028467; -.
DR eggNOG; KOG2119; Eukaryota.
DR GeneTree; ENSGT00390000010998; -.
DR HOGENOM; CLU_006322_1_1_1; -.
DR InParanoid; Q69ZF3; -.
DR OMA; HDLGAPN; -.
DR OrthoDB; 207392at2759; -.
DR PhylomeDB; Q69ZF3; -.
DR TreeFam; TF313888; -.
DR BRENDA; 3.2.1.45; 3474.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR UniPathway; UPA00222; -.
DR UniPathway; UPA00296; -.
DR BioGRID-ORCS; 230101; 3 hits in 73 CRISPR screens.
DR PRO; PR:Q69ZF3; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q69ZF3; protein.
DR Bgee; ENSMUSG00000028467; Expressed in medial dorsal nucleus of thalamus and 243 other tissues.
DR ExpressionAtlas; Q69ZF3; baseline and differential.
DR Genevisible; Q69ZF3; MM.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0042406; C:extrinsic component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0090498; C:extrinsic component of Golgi membrane; IDA:UniProtKB.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
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:0050295; F:steryl-beta-glucosidase activity; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0021954; P:central nervous system neuron development; ISS:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IMP:UniProtKB.
DR GO; GO:0006680; P:glucosylceramide catabolic process; IDA:UniProtKB.
DR GO; GO:0016139; P:glycoside catabolic process; ISO:MGI.
DR GO; GO:0030259; P:lipid glycosylation; IDA:UniProtKB.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IMP:UniProtKB.
DR GO; GO:0097035; P:regulation of membrane lipid distribution; IMP:UniProtKB.
DR GO; GO:0031113; P:regulation of microtubule polymerization; IMP:UniProtKB.
DR Gene3D; 1.50.10.10; -; 1.
DR InterPro; IPR008928; 6-hairpin_glycosidase_sf.
DR InterPro; IPR012341; 6hp_glycosidase-like_sf.
DR InterPro; IPR014551; B_Glucosidase_GBA2-typ.
DR InterPro; IPR006775; GH116_catalytic.
DR InterPro; IPR024462; GH116_N.
DR Pfam; PF04685; DUF608; 1.
DR Pfam; PF12215; Glyco_hydr_116N; 1.
DR PIRSF; PIRSF028944; Beta_gluc_GBA2; 1.
DR SUPFAM; SSF48208; SSF48208; 1.
PE 1: Evidence at protein level;
KW Cholesterol metabolism; Endoplasmic reticulum; Glycosidase;
KW Glycosyltransferase; Golgi apparatus; Hydrolase; Lipid metabolism;
KW Membrane; Phosphoprotein; Reference proteome; Sphingolipid metabolism;
KW Steroid metabolism; Sterol metabolism; Transferase.
FT CHAIN 1..918
FT /note="Non-lysosomal glucosylceramidase"
FT /id="PRO_0000283759"
FT REGION 886..918
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 893
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 385
FT /note="V -> I (in Ref. 2; BAC40785)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 918 AA; 103294 MW; EABE7B50B96B0B59 CRC64;
MVTCVPASEQ VGCAERDSQV YCEDTGGTEA VRVTDCGSPE DSGPQDEPSY CNSEDSGQLM
ASYEGKARGY QVPPFGWRIC LAHEFAEKRR PFQANNISLS NLVKHLGMGL RYLKWWYRKT
HVEKKTPFID MLNSLPLRQI YGCPLGGIGG GTITRGWRGQ FCRWQLNPGM YQHQTVIADQ
FIVCLRRDGR TVYQQVLSLE LPNVLRSWNW GLCGYFAFYH ALYPRAWTVY QLPGQNVTLT
CRQVTPILPH DYQDSSLPVG VFVWDVENEG DETLDVSITF SMRNGLGGED DAAGSLWNEP
FRLEQGGTTV QGLLLHHPTP PNPYTMAVAA RCTADTTVTH TTAFDPNGTG QQVWQDLLQD
GQLDSPAGQS TPTQKGEGIA GAVCVSSKLL PRSRCCLEFS LAWDMPKIMF GAKSQVHYRR
YTRFFGSDGD VAPALSHYAL CHYADWEDRI SAWQNPVLDD RTLPAWYKSA LFNELYFLAD
GGTVWLEVPA DSLPEGLGGS MRQLRSTLQD YGRFGYLEGQ EYRMYNTYDV HFYASFALVM
LWPKLELSLQ YDMALATLKE DLTRRRYLMS GVVAPVKRRN VIPHDIGDPD DEPWLRVNAY
LIHDTADWKD LNLKFVLQIY RDYYLTGDQG FLEDMWPVCL AVMESEMKFD KDQDGLIENG
GYADQTYDAW VTTGPSAYCG GLWLAAVAVM VQMAVLCGAQ DVQERFASIL CRGREAYERL
LWNGRYYNYD SSSHPQSRSI MSDQCAGQWF LRACGLGEGD TEVFPTLHVV RALQTIFELN
VQAFAGGAMG AVNGMHPHGV PDRSSVQSDE VWVGVVYGLA ATMIQEGLTW EGFRTAEGCY
RTVWERLGLA FQTPEAYCQQ QVFRSLAYMR PLSIWAMQLA LQQQQHKKSR RPSVTQGTGL
STQPECGPKR SLANLNSE
