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Q9H227 (GBA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytosolic beta-glucosidase

EC=3.2.1.21
Alternative name(s):
Cytosolic beta-glucosidase-like protein 1
Gene names
Name:GBA3
Synonyms:CBG, CBGL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length469 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Glycosidase probably involved in the intestinal absorption and metabolism of dietary flavonoid glycosides. Able to hydrolyze a broad variety of glycosides including phytoestrogens, flavonols, flavones, flavanones and cyanogens. Possesses beta-glycosylceramidase activity and may be involved in a nonlysosomal catabolic pathway of glycosylceramide. Ref.3 Ref.8 Ref.9

Catalytic activity

Hydrolysis of terminal, non-reducing beta-D-glucosyl residues with release of beta-D-glucose.

Enzyme regulation

Inhibited by 2,4-dinitrophenyl-2-fluoro-2-deoxy-beta-D-glucopyranoside and sodium taurocholate. Ref.2 Ref.3

Subcellular location

Cytoplasmcytosol Ref.8 Ref.9.

Tissue specificity

Present in small intestine (at protein level). Expressed in liver, small intestine, colon, spleen and kidney. Down-regulated in renal cell carcinomas and hepatocellular carcinomas. Ref.1 Ref.8

Post-translational modification

The N-terminus is blocked.

Sequence similarities

Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.

Biophysicochemical properties

Kinetic parameters:

KM=40 µM for 4-methylumbelliferyl-beta-D-glucopyranoside Ref.2 Ref.3

KM=50 µM for 4-methylumbelliferyl-beta-D-galactopyranoside

KM=370 µM for 4-nitrophenyl-beta-D-fucopyranoside

KM=570 µM for 4-nitrophenyl-alpha-D-arabinopyranoside

KM=1.76 mM for 4-nitrophenyl-beta-D-glucopyranoside

KM=3.14 mM for 4-nitrophenyl-beta-D-galactopyranoside

KM=1.58 mM for 4-nitrophenyl-beta-D-xylopyranoside

KM=52.6 mM for 4-nitrophenyl-beta-L-arabinopyranoside

KM=35 µM for genistein-7-glucoside

KM=118 µM for daidzein-7-glucoside

KM=31.8 µM for quercetin-4'-glucoside

KM=42.2 µM for quercetin-7-glucoside

KM=21.5 µM for apigenin-7-glucoside

KM=10 µM for luteolin-4'-glucoside

KM=50 µM for luteolin-7-glucoside

KM=432 µM for naringenin-7-glucoside

KM=253 µM for eriodictyol-7-glucoside

Vmax=10 µmol/min/mg enzyme toward 4-nitrophenyl-beta-D-glucopyranoside

Vmax=1.73 µmol/min/mg enzyme toward genistein-7-glucoside

Vmax=2.75 µmol/min/mg enzyme toward daidzein-7-glucoside

Vmax=1.19 µmol/min/mg enzyme toward quercetin-4'-glucoside

Vmax=0.77 µmol/min/mg enzyme toward quercetin-7-glucoside

Vmax=1.30 µmol/min/mg enzyme toward apigenin-7-glucoside

Vmax=1.30 µmol/min/mg enzyme toward luteolin-4'-glucoside

Vmax=2.85 µmol/min/mg enzyme toward luteolin-7-glucoside

Vmax=0.93 µmol/min/mg enzyme toward naringenin-7-glucoside

Vmax=0.90 µmol/min/mg enzyme toward eriodictyol-7-glucoside

pH dependence:

Optimum pH is 6.5. Active from pH 5 to 7.5. Activity decreases sharply with increasing acidity and is less than 4% at pH 4.

Temperature dependence:

Optimum temperature is 50 degrees Celsius. Stable more than 24 hours at 37 degrees Celsius. Loses activity at 58 degrees Celsius.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9H227-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9H227-2)

The sequence of this isoform differs from the canonical sequence as follows:
     95-401: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 469469Cytosolic beta-glucosidase
PRO_0000063908

Regions

Region424 – 4252Substrate binding By similarity

Sites

Active site1651Proton donor Potential
Active site3731Nucleophile Potential
Binding site171Substrate
Binding site1201Substrate
Binding site1641Substrate
Binding site3091Substrate
Binding site4171Substrate

Natural variations

Alternative sequence95 – 401307Missing in isoform 2.
VSP_015835
Natural variant1061D → N Rare polymorphism. Ref.12
VAR_023587
Natural variant1721M → I.
Corresponds to variant rs36090352 [ dbSNP | Ensembl ].
VAR_049298
Natural variant2131R → P.
Corresponds to variant rs17612341 [ dbSNP | Ensembl ].
VAR_023588
Natural variant3541C → R.
Corresponds to variant rs16873108 [ dbSNP | Ensembl ].
VAR_023589

Experimental info

Mutagenesis1651E → D: Reduces catalytic activity 2-fold. Ref.9 Ref.11
Mutagenesis1651E → Q: Loss of catalytic activity. Ref.9 Ref.11
Mutagenesis1681V → Y: No change in temperature or pH dependence. Decrease in specific activity. Ref.7
Mutagenesis2251F → S: Decrease in specific activity. Ref.7
Mutagenesis3081Y → F or A: Decrease in specific activity. Ref.7
Mutagenesis3731E → D: Reduces catalytic activity 2-fold. Ref.9
Mutagenesis3731E → Q: Loss of catalytic activity. Ref.9
Sequence conflict291P → L in AAH70188. Ref.6
Sequence conflict1341L → W in AAG39217. Ref.3
Sequence conflict3091Y → C in BAD96683. Ref.5
Sequence conflict3211K → R in BAD96683. Ref.5
Sequence conflict3261I → T in CAC08178. Ref.2

Secondary structure

................................................................................ 469
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 11, 2005. Version 2.
Checksum: 9036455485CE2E2F

FASTA46953,696
        10         20         30         40         50         60 
MAFPAGFGWA AATAAYQVEG GWDADGKGPC VWDTFTHQGG ERVFKNQTGD VACGSYTLWE 

        70         80         90        100        110        120 
EDLKCIKQLG LTHYRFSLSW SRLLPDGTTG FINQKGIDYY NKIIDDLLKN GVTPIVTLYH 

       130        140        150        160        170        180 
FDLPQTLEDQ GGWLSEAIIE SFDKYAQFCF STFGDRVKQW ITINEANVLS VMSYDLGMFP 

       190        200        210        220        230        240 
PGIPHFGTGG YQAAHNLIKA HARSWHSYDS LFRKKQKGMV SLSLFAVWLE PADPNSVSDQ 

       250        260        270        280        290        300 
EAAKRAITFH LDLFAKPIFI DGDYPEVVKS QIASMSQKQG YPSSRLPEFT EEEKKMIKGT 

       310        320        330        340        350        360 
ADFFAVQYYT TRLIKYQENK KGELGILQDA EIEFFPDPSW KNVDWIYVVP WGVCKLLKYI 

       370        380        390        400        410        420 
KDTYNNPVIY ITENGFPQSD PAPLDDTQRW EYFRQTFQEL FKAIQLDKVN LQVYCAWSLL 

       430        440        450        460 
DNFEWNQGYS SRFGLFHVDF EDPARPRVPY TSAKEYAKII RNNGLEAHL 

« Hide

Isoform 2 [UniParc].

Checksum: AC2A05DB957E6997
Show »

FASTA16218,265

References

« Hide 'large scale' references
[1]"Molecular cloning and expression of a novel klotho-related protein."
Yahata K., Mori K., Arai H., Koide S., Ogawa Y., Mukoyama M., Sugawara A., Ozaki S., Tanaka I., Nabeshima Y., Nakao K.
J. Mol. Med. 78:389-394(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Fetal liver.
[2]"Cloning and characterization of human liver cytosolic beta-glycosidase."
de Graaf M., van Veen I.C., van der Meulen-Muileman I.H., Gerritsen W.R., Pinedo H.M., Haisma H.J.
Biochem. J. 356:907-910(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
Tissue: Liver.
[3]"Functional expression of human liver cytosolic beta-glucosidase in Pichia pastoris. Insights into its role in the metabolism of dietary glucosides."
Berrin J.-G., McLauchlan W.R., Needs P., Williamson G., Puigserver A., Kroon P.A., Juge N.
Eur. J. Biochem. 269:249-258(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, BLOCKAGE OF N-TERMINUS, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
Tissue: Liver.
[4]Hays W.S., VanderJagt D.J., Glew R.H., Johnston D.E.
Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[5]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Small intestine.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Kidney and Liver.
[7]"Substrate (aglycone) specificity of human cytosolic beta-glucosidase."
Berrin J.-G., Czjzek M., Kroon P.A., McLauchlan W.R., Puigserver A., Williamson G., Juge N.
Biochem. J. 373:41-48(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF VAL-168; PHE-225 AND TYR-308.
[8]"Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans."
Nemeth K., Plumb G.W., Berrin J.-G., Juge N., Jacob R., Naim H.Y., Williamson G., Swallow D.M., Kroon P.A.
Eur. J. Nutr. 42:29-42(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]"Klotho-related protein is a novel cytosolic neutral beta-glycosylceramidase."
Hayashi Y., Okino N., Kakuta Y., Shikanai T., Tani M., Narimatsu H., Ito M.
J. Biol. Chem. 282:30889-30900(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH GLUCOSE AND GALACTOSE, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF GLU-165 AND GLU-373.
[10]"The crystal structure of human cytosolic beta-glucosidase unravels the substrate aglycone specificity of a family 1 glycoside hydrolase."
Tribolo S., Berrin J.G., Kroon P.A., Czjzek M., Juge N.
J. Mol. Biol. 370:964-975(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
[11]"Crystal structure of the covalent intermediate of human cytosolic beta-glucosidase."
Noguchi J., Hayashi Y., Baba Y., Okino N., Kimura M., Ito M., Kakuta Y.
Biochem. Biophys. Res. Commun. 374:549-552(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH GLUCOSE, MUTAGENESIS OF GLU-165.
[12]"Mutations in the gene encoding cytosolic beta-glucosidase in Gaucher disease."
Beutler E., Beutler L., West C.
J. Lab. Clin. Med. 144:65-68(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASN-106.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB017913 mRNA. Translation: BAB18741.1.
AJ278964 mRNA. Translation: CAC08178.1.
AF317840 mRNA. Translation: AAG39217.1.
AF323990 mRNA. Translation: AAL37305.1.
AK222963 mRNA. Translation: BAD96683.1.
BC029362 mRNA. Translation: AAH29362.1.
BC070188 mRNA. Translation: AAH70188.1.
BC101829 mRNA. Translation: AAI01830.1.
BC109377 mRNA. Translation: AAI09378.1.
RefSeqNP_001121904.1. NM_001128432.2.
NP_001264154.1. NM_001277225.1.
NP_066024.1. NM_020973.4.
UniGeneHs.653107.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2E9LX-ray1.60A1-469[»]
2E9MX-ray1.80A1-469[»]
2JFEX-ray2.70X1-469[»]
2ZOXX-ray1.90A1-469[»]
3VKKX-ray2.00A1-469[»]
ProteinModelPortalQ9H227.
SMRQ9H227. Positions 1-466.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121753. 2 interactions.
IntActQ9H227. 1 interaction.

Chemistry

BindingDBQ9H227.
ChEMBLCHEMBL3865.

Protein family/group databases

CAZyGH1. Glycoside Hydrolase Family 1.

PTM databases

PhosphoSiteQ9H227.

Polymorphism databases

DMDM77416427.

Proteomic databases

PRIDEQ9H227.

Protocols and materials databases

DNASU57733.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID57733.
KEGGhsa:57733.
UCSCuc031sdv.1. human. [Q9H227-1]
uc031sdw.1. human. [Q9H227-2]

Organism-specific databases

CTD57733.
GeneCardsGC04P022694.
HGNCHGNC:19069. GBA3.
MIM606619. gene.
neXtProtNX_Q9H227.
PharmGKBPA134861643.
GenAtlasSearch...

Phylogenomic databases

HOVERGENHBG053101.
InParanoidQ9H227.
KOK05350.
PhylomeDBQ9H227.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
SABIO-RKQ9H227.

Gene expression databases

CleanExHS_GBA3.
GenevestigatorQ9H227.

Family and domain databases

Gene3D3.20.20.80. 1 hit.
InterProIPR001360. Glyco_hydro_1.
IPR018120. Glyco_hydro_1_AS.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PANTHERPTHR10353. PTHR10353. 1 hit.
PfamPF00232. Glyco_hydro_1. 1 hit.
[Graphical view]
PRINTSPR00131. GLHYDRLASE1.
SUPFAMSSF51445. SSF51445. 1 hit.
PROSITEPS00653. GLYCOSYL_HYDROL_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9H227.
GeneWikiGBA3.
GenomeRNAi57733.
NextBio64698.
PROQ9H227.
SOURCESearch...

Entry information

Entry nameGBA3_HUMAN
AccessionPrimary (citable) accession number: Q9H227
Secondary accession number(s): Q32LY7 expand/collapse secondary AC list , Q3MIH4, Q53GG8, Q6NSF4, Q8NHT8, Q9H3T4, Q9H4C6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: October 11, 2005
Last modified: April 16, 2014
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries