ID   GBA3_PONAB              Reviewed;         469 AA.
AC   Q5RF65;
DT   11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   24-JAN-2024, entry version 95.
DE   RecName: Full=Cytosolic beta-glucosidase {ECO:0000305};
DE            EC=3.2.1.21 {ECO:0000250|UniProtKB:Q9H227};
DE   AltName: Full=Cytosolic galactosylceramidase {ECO:0000305};
DE            EC=3.2.1.46 {ECO:0000250|UniProtKB:Q9H227};
DE   AltName: Full=Cytosolic glucosylceramidase {ECO:0000305};
DE            EC=3.2.1.45 {ECO:0000250|UniProtKB:Q9H227};
DE   AltName: Full=Cytosolic glycosylceramidase {ECO:0000250|UniProtKB:Q9H227};
DE            Short=Cytosolic GCase {ECO:0000250|UniProtKB:Q9H227};
GN   Name=GBA3 {ECO:0000250|UniProtKB:Q9H227};
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Neutral cytosolic beta-glycosidase with a broad substrate
CC       specificity that could play a role in the catabolism of
CC       glycosylceramides. Has a significant glucosylceramidase activity in
CC       vitro. However, that activity is relatively low and its significance in
CC       vivo is not clear. Hydrolyzes galactosylceramides/GalCers,
CC       glucosylsphingosines/GlcSphs and galactosylsphingosines/GalSphs.
CC       However, the in vivo relevance of these activities is unclear. It can
CC       also hydrolyze a broad variety of dietary glycosides including
CC       phytoestrogens, flavonols, flavones, flavanones and cyanogens in vitro
CC       and could therefore play a role in the metabolism of xenobiotics.
CC       Possesses transxylosylase activity in vitro using xylosylated
CC       ceramides/XylCers (such as beta-D-xylosyl-(1<->1')-N-acylsphing-4-
CC       enine) as xylosyl donors and cholesterol as acceptor. Could also play a
CC       role in the catabolism of cytosolic sialyl free N-glycans.
CC       {ECO:0000250|UniProtKB:Q9H227}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Hydrolysis of terminal, non-reducing beta-D-glucosyl residues
CC         with release of beta-D-glucose.; EC=3.2.1.21;
CC         Evidence={ECO:0000250|UniProtKB:Q9H227};
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:Q9H227};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13270;
CC         Evidence={ECO:0000250|UniProtKB:Q9H227};
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:Q9H227};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14298;
CC         Evidence={ECO:0000250|UniProtKB:Q9H227};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=beta-D-glucosyl-(1<->1)-sphing-4-enine + H2O = D-glucose +
CC         sphing-4-enine; Xref=Rhea:RHEA:59288, ChEBI:CHEBI:4167,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:57756, ChEBI:CHEBI:83992;
CC         Evidence={ECO:0000250|UniProtKB:Q9H227};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59289;
CC         Evidence={ECO:0000250|UniProtKB:Q9H227};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=beta-D-glucosyl-(1<->1)-N-octadecanoylsphing-4-enine + H2O =
CC         D-glucose + N-octadecanoylsphing-4-enine; Xref=Rhea:RHEA:59284,
CC         ChEBI:CHEBI:4167, ChEBI:CHEBI:15377, ChEBI:CHEBI:72961,
CC         ChEBI:CHEBI:84719; Evidence={ECO:0000250|UniProtKB:Q9H227};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59285;
CC         Evidence={ECO:0000250|UniProtKB:Q9H227};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=beta-D-galactosyl-(1<->1)-sphing-4-enine + H2O = D-galactose +
CC         sphing-4-enine; Xref=Rhea:RHEA:43908, ChEBI:CHEBI:4139,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:57756, ChEBI:CHEBI:57934;
CC         Evidence={ECO:0000250|UniProtKB:Q9H227};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43909;
CC         Evidence={ECO:0000250|UniProtKB:Q9H227};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=beta-D-galactosyl-(1<->1')-N-octadecanoylsphing-4-enine + H2O
CC         = D-galactose + N-octadecanoylsphing-4-enine; Xref=Rhea:RHEA:59292,
CC         ChEBI:CHEBI:4139, ChEBI:CHEBI:15377, ChEBI:CHEBI:72961,
CC         ChEBI:CHEBI:84720; Evidence={ECO:0000250|UniProtKB:Q9H227};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59293;
CC         Evidence={ECO:0000250|UniProtKB:Q9H227};
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:Q9H227};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70240;
CC         Evidence={ECO:0000250|UniProtKB:Q9H227};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70241;
CC         Evidence={ECO:0000250|UniProtKB:Q9H227};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:Q9H227}.
CC   -!- PTM: The N-terminus is blocked. {ECO:0000250|UniProtKB:Q9H227}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 1 family. Klotho
CC       subfamily. {ECO:0000305}.
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DR   EMBL; CR857296; CAH89592.1; -; mRNA.
DR   RefSeq; NP_001124705.1; NM_001131233.1.
DR   AlphaFoldDB; Q5RF65; -.
DR   SMR; Q5RF65; -.
DR   STRING; 9601.ENSPPYP00000016355; -.
DR   CAZy; GH1; Glycoside Hydrolase Family 1.
DR   Ensembl; ENSPPYT00000017020.3; ENSPPYP00000016355.2; ENSPPYG00000014639.3.
DR   GeneID; 100171553; -.
DR   KEGG; pon:100171553; -.
DR   CTD; 57733; -.
DR   eggNOG; KOG0626; Eukaryota.
DR   GeneTree; ENSGT00940000160460; -.
DR   HOGENOM; CLU_001859_1_3_1; -.
DR   InParanoid; Q5RF65; -.
DR   OMA; DPSWPIC; -.
DR   OrthoDB; 3373839at2759; -.
DR   TreeFam; TF314803; -.
DR   Proteomes; UP000001595; Chromosome 4.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0004565; F:beta-galactosidase activity; ISS:UniProtKB.
DR   GO; GO:0008422; F:beta-glucosidase activity; ISS:UniProtKB.
DR   GO; GO:0004336; F:galactosylceramidase activity; ISS:UniProtKB.
DR   GO; GO:0004348; F:glucosylceramidase activity; ISS:UniProtKB.
DR   GO; GO:0017042; F:glycosylceramidase activity; ISS:UniProtKB.
DR   GO; GO:0102483; F:scopolin beta-glucosidase activity; IEA:UniProtKB-EC.
DR   GO; GO:1901805; P:beta-glucoside catabolic process; ISS:UniProtKB.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR   GO; GO:0006683; P:galactosylceramide catabolic process; ISS:UniProtKB.
DR   GO; GO:0006680; P:glucosylceramide catabolic process; ISS:UniProtKB.
DR   Gene3D; 3.20.20.80; Glycosidases; 1.
DR   InterPro; IPR001360; Glyco_hydro_1.
DR   InterPro; IPR033132; Glyco_hydro_1_N_CS.
DR   InterPro; IPR017853; Glycoside_hydrolase_SF.
DR   PANTHER; PTHR10353:SF291; CYTOSOLIC BETA-GLUCOSIDASE; 1.
DR   PANTHER; PTHR10353; GLYCOSYL HYDROLASE; 1.
DR   Pfam; PF00232; Glyco_hydro_1; 1.
DR   PRINTS; PR00131; GLHYDRLASE1.
DR   SUPFAM; SSF51445; (Trans)glycosidases; 1.
DR   PROSITE; PS00653; GLYCOSYL_HYDROL_F1_2; 1.
PE   2: Evidence at transcript level;
KW   Cytoplasm; Glycosidase; Hydrolase; Lipid metabolism; Reference proteome.
FT   CHAIN           1..469
FT                   /note="Cytosolic beta-glucosidase"
FT                   /id="PRO_0000063909"
FT   ACT_SITE        165
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        373
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255"
FT   BINDING         17
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         120
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         164
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         309
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         417
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         424..425
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   469 AA;  53747 MW;  EC6DFA9543EA6843 CRC64;
     MAFPVGFGWA AATAAYQVEG GWDADGKGPC VWDTFTHQGG ERVFKNQTGD VACGSYTLWE
     EDLKCIKQLG LTHYRFSLSW SRLLPDGTTG FINQKGIDYY NKIIDDLLKN GVTPIVTLYH
     FDLPQALEDQ GGWLSEAIIE SFDKYAQFCF STFGDRVKKW ITINEANVLS VMSYDLGMFP
     PGIPHFGTGG YQAAHNLIKA HARSWHSYNS LFRKEQKGMV SLSLFAVWLE PADPNSVSDQ
     EAAKRAITFH LDLFAKPIFI DGDYPEIVKS QIASMSQKQG YPSSRLPEFT EEEKKMIKGT
     ADFFAVQYYT TRLIKYQENK KGELGILQDA EIEFFPDPSW KNVDWIYVVP WGVRKLLKYI
     KDTYNNPVIY ITENGFPQSD PAPLDDTQRW EYFRQTFQEL FKAIQLDKVN LQVYCAWSLL
     DNFEWNQGYS SRFGLFHVDF EDPARPRVPY TSAKEYAKVI RNNGLEAHL
//