{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q69ZF3","secondaryAccessions":["Q6PGM3","Q8BTN9"],"uniProtkbId":"GBA2_MOUSE","entryAudit":{"firstPublicDate":"2007-04-03","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2007-04-03","entryVersion":141,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Mus musculus","commonName":"Mouse","taxonId":10090,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Glires","Rodentia","Myomorpha","Muroidea","Muridae","Murinae","Mus","Mus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Non-lysosomal glucosylceramidase"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"23250757"}],"value":"NLGase"}],"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17080196"}],"value":"3.2.1.45"}]},"alternativeNames":[{"fullName":{"value":"Beta-glucocerebrosidase 2"},"shortNames":[{"value":"Beta-glucosidase 2"}]},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"17080196"}],"value":"Bile acid beta-glucosidase GBA2"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9HCG7"}],"value":"Bile acid glucosyl transferase GBA2"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"26724485"}],"value":"Cholesterol glucosyltransferase GBA2"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26724485"}],"value":"2.4.1.-"}]},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"26724485"}],"value":"Cholesteryl-beta-glucosidase GBA2"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26724485"}],"value":"3.2.1.-"}]},{"fullName":{"value":"Glucosylceramidase 2"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Non-lysosomal cholesterol glycosyltransferase"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Non-lysosomal galactosylceramidase"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32144204"}],"value":"3.2.1.46"}]},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Non-lysosomal glycosylceramidase"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"MGI","id":"MGI:2654325"}],"value":"Gba2"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"BAD32491.1"}],"value":"Kiaa1605"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17080196"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23250757"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25803043"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26724485"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32144204"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"23250757"}],"value":"Non-lysosomal glucosylceramidase that catalyzes the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine) to free glucose and ceramides (such as N-acylsphing-4-enine) (PubMed:17080196, PubMed:23250757). GlcCers are membrane glycosphingolipids that have a wide intracellular distribution (PubMed:23250757). They are the main precursors of more complex glycosphingolipids that play a role in cellular growth, differentiation, adhesion, signaling, cytoskeletal dynamics and membrane properties (PubMed:25803043). Also involved in the transglucosylation of cholesterol, transferring glucose from GlcCer, thereby modifying its water solubility and biological properties (PubMed:26724485, PubMed:32144204). Under specific conditions, may catalyze the reverse reaction, transferring glucose from cholesteryl-3-beta-D-glucoside to ceramide (such as N-acylsphing-4-enine) (PubMed:26724485, PubMed:32144204). May play a role in the metabolism of bile acids (PubMed:17080196). Able to hydrolyze bile acid 3-O-glucosides as well as to produce bile acid-glucose conjugates thanks to a bile acid glucosyl transferase activity (PubMed:17080196). Catalyzes the hydrolysis of galactosylceramides/GalCers (such as beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine), as well as galactosyl transfer between GalCers and cholesterol in vitro with lower activity compared with their activity against GlcCers (PubMed:32144204)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine + H2O = an N-acylsphing-4-enine + 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association and requires the presence of lipids (PubMed:23250757). Inhibited by N-(adamantanemethyloxypentyl)-deoxynojirimycin/AMP-DNM (PubMed:26724485). Inhibited by its product sphingosine/N-acylsphing-4-enine in a feedback loop (PubMed:28258214). Also inhibited by other non-acetylated sphingoid bases and their derivatives but not by sphingosine-1-phosphate and complex sphingolipids (PubMed:28258214)"}],"commentType":"ACTIVITY REGULATION"},{"commentType":"BIOPHYSICOCHEMICAL PROPERTIES","phDependence":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26724485"}],"value":"Optimum pH is between 6.0 and 7.0."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17080196"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23250757"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26724485"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"32144204"}],"value":"Lipid metabolism; sphingolipid metabolism"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26724485"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"32144204"}],"value":"Steroid metabolism; cholesterol metabolism"}],"commentType":"PATHWAY"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9HCG7"}],"value":"Localization to the plasma membrane and alternative topologies have also been reported"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23250757"}],"value":"Endoplasmic reticulum membrane","id":"SL-0097"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23250757"}],"value":"Peripheral membrane protein","id":"SL-9903"},"orientation":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23250757"}],"value":"Cytoplasmic side","id":"SL-9910"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23250757"}],"value":"Golgi apparatus membrane","id":"SL-0134"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23250757"}],"value":"Peripheral membrane protein","id":"SL-9903"},"orientation":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23250757"}],"value":"Cytoplasmic side","id":"SL-9910"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17080196"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23250757"}],"value":"Widely expressed at low level (PubMed:17080196). Highly expressed in testis and brain (PubMed:17080196). Ubiquitously expressed in the brain (at protein level) (PubMed:23250757). Expressed by Sertoli cells (at protein level) (PubMed:17080196)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17080196"}],"value":"Homozygous knockout mice display an accumulation of glucosylceramides in testis, brain and liver (PubMed:17080196). The accumulation of glucosylceramides in Sertoli cells alters sperm shape and males exhibit impaired fertility (PubMed:17080196). Despite the bile acid glucosidase and transferase activities measured in vitro, bile acid metabolism is normal in knockout mice (PubMed:17080196). No obvious neurological symptoms, organomegaly or lifespan alteration are observed (PubMed:17080196). Cholesterol metabolism and protein glycosylation are also normal in these mice (PubMed:17080196)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the non-lysosomal glucosylceramidase family"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"BAD32491.1","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":918,"modifier":"EXACT"}},"description":"Non-lysosomal glucosylceramidase","featureId":"PRO_0000283759"},{"type":"Region","location":{"start":{"value":886,"modifier":"EXACT"},"end":{"value":918,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":892,"modifier":"EXACT"},"end":{"value":904,"modifier":"EXACT"}},"description":"Polar residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Modified residue","location":{"start":{"value":893,"modifier":"EXACT"},"end":{"value":893,"modifier":"EXACT"}},"description":"Phosphoserine","evidences":[{"evidenceCode":"ECO:0007744","source":"PubMed","id":"21183079"}]},{"type":"Sequence conflict","location":{"start":{"value":385,"modifier":"EXACT"},"end":{"value":385,"modifier":"EXACT"}},"description":"in Ref. 2; BAC40785","evidences":[{"evidenceCode":"ECO:0000305"}],"alternativeSequence":{"originalSequence":"V","alternativeSequences":["I"]}}],"keywords":[{"id":"KW-0153","category":"Biological process","name":"Cholesterol metabolism"},{"id":"KW-0256","category":"Cellular component","name":"Endoplasmic reticulum"},{"id":"KW-0326","category":"Molecular function","name":"Glycosidase"},{"id":"KW-0328","category":"Molecular function","name":"Glycosyltransferase"},{"id":"KW-0333","category":"Cellular component","name":"Golgi apparatus"},{"id":"KW-0378","category":"Molecular function","name":"Hydrolase"},{"id":"KW-0443","category":"Biological process","name":"Lipid metabolism"},{"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"id":"KW-0597","category":"PTM","name":"Phosphoprotein"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0746","category":"Biological process","name":"Sphingolipid metabolism"},{"id":"KW-0753","category":"Biological process","name":"Steroid metabolism"},{"id":"KW-1207","category":"Biological process","name":"Sterol metabolism"},{"id":"KW-0808","category":"Molecular function","name":"Transferase"}],"references":[{"referenceNumber":1,"citation":{"id":"15368895","citationType":"journal article","authors":["Okazaki N.","Kikuno R.","Ohara R.","Inamoto S.","Koseki H.","Hiraoka S.","Saga Y.","Seino S.","Nishimura M.","Kaisho T.","Hoshino K.","Kitamura H.","Nagase T.","Ohara O.","Koga H."],"citationCrossReferences":[{"database":"PubMed","id":"15368895"},{"database":"DOI","id":"10.1093/dnares/11.3.205"}],"title":"Prediction of the coding sequences of mouse homologues of KIAA gene: IV. 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