Reviewed, UniProtKB/Swiss-Prot Q9H227 (GBA3_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	469 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.
Catalytic activity	Hydrolysis of terminal, non-reducing beta-D-glucose residues with release of beta-D-glucose.
Enzyme regulation	Inhibited by 2,4-dinitrophenyl-2-fluoro-2-deoxy-beta-D-glucopyranoside and sodium taurocholate.
Subcellular location	Cytoplasm › cytosol.
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.
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 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.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Glycosidase Hydrolase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	glycoside catabolic process Ref.2 Inferred from direct assay. Source: UniProtKB
Molecular function	beta-galactosidase activity Ref.2 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 469

469

Cytosolic beta-glucosidase

Sites

Active site

165

1

Proton donor Potential

Active site

373

1

Nucleophile Potential

Natural variations

Alternative sequence

95 – 401

307

Missing in isoform 2.

Natural variant

106

1

D → N Rare polymorphism.

Natural variant

213

1

R → P: dbSNP rs17612341.

Natural variant

354

1

C → R: dbSNP rs16873108.

Experimental info

Mutagenesis

168

1

V → Y: No change in temperature or pH dependence. Decrease in specific activity

Mutagenesis

225

1

F → S: Decrease in specific activity

Mutagenesis

308

1

Y → F or A: Decrease in specific activity

Sequence conflict

29

1

P → L in AAH70188. Ref.6

Sequence conflict

134

1

L → W in AAG39217. Ref.3

Sequence conflict

309

1

Y → C in BAD96683. Ref.5

Sequence conflict

321

1

K → R in BAD96683. Ref.5

Sequence conflict

326

1

I → T in CAC08178. Ref.2

Secondary structure

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469

Helix Strand Turn

Details...

Beta strand

8 – 12

5

Helix

15 – 18

4

Helix

24 – 26

3

Helix

31 – 38

8

Beta strand

40 – 43

4

Helix

44 – 46

3

Beta strand

49 – 51

3

Turn

55 – 57

3

Helix

59 – 69

11

Beta strand

72 – 77

6

Helix

80 – 83

4

Helix

94 – 109

16

Beta strand

113 – 121

9

Helix

125 – 129

5

Helix

132 – 134

3

Helix

138 – 153

16

Turn

154 – 156

3

Beta strand

159 – 164

6

Helix

166 – 174

9

Turn

186 – 188

3

Helix

189 – 211

23

Helix

213 – 216

4

Beta strand

219 – 221

3

Beta strand

223 – 233

11

Helix

237 – 250

14

Helix

252 – 259

8

Helix

266 – 278

13

Helix

291 – 297

7

Beta strand

302 – 316

15

Helix

326 – 330

5

Beta strand

332 – 335

4

Helix

351 – 363

13

Beta strand

369 – 374

6

Beta strand

378 – 381

4

Helix

387 – 405

19

Beta strand

411 – 417

7

Helix

425 – 430

6

Beta strand

435 – 438

4

Beta strand

447 – 449

3

Helix

451 – 462

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 11, 2005. Version 2. Checksum: 9036455485CE2E2F	FASTA	469	53,696
	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
	Isoform 2 [UniParc]. Checksum: AC2A05DB957E6997		162	18,265
	10 20 30 40 50 60 MAFPAGFGWA AATAAYQVEG GWDADGKGPC VWDTFTHQGG ERVFKNQTGD VACGSYTLWE 70 80 90 100 110 120 EDLKCIKQLG LTHYRFSLSW SRLLPDGTTG FINQKAIQLD KVNLQVYCAW SLLDNFEWNQ 130 140 150 160 GYSSRFGLFH VDFEDPARPR VPYTSAKEYA KIIRNNGLEA HL

References

	« Hide 'large scale' referencesShow '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: 11043382] [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: 11389701] [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: 11784319] [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: 15489334] [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: 12667141] [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: 12594539] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]	"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: 15322500] [Abstract] Cited for: VARIANT ASN-106.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

RefSeq

NP_001121904.1.
NP_066024.1.

UniGene

Hs.653107

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2E9L	X-ray	1.60	A	1-469	[»]
2E9M	X-ray	1.80	A	1-469	[»]
2JFE	X-ray	2.70	X	1-469	[»]

ModBase

Search...

Genome annotation databases

Ensembl

ENSG00000176201. Homo sapiens. [Contig view]

GeneID

57733.

Organism-specific databases

H-InvDB

HIX0004133.

HGNC

HGNC:19069. GBA3.

MIM

606619. gene.

PharmGKB