Reviewed, UniProtKB/Swiss-Prot Q9HCG7 (GBA2_HUMAN)

Names and origin

Protein names

Recommended name:
    Non-lysosomal glucosylceramidase
      Short name=NLGase
    EC=3.2.1.45
Alternative name(s):
    Glucosylceramidase 2
    Beta-glucocerebrosidase 2
      Short name=Beta-glucosidase 2

Gene names

Name:	GBA2
Synonyms:	KIAA1605
ORF Names:	AD035

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	927 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Non-lysosomal glucosylceramidase that catalyzes the conversion of glucosylceramide to free glucose and ceramide. Involved in sphingomyelin generation and prevention of glycolipid accumulation. May also catalyze the hydrolysis of bile acid 3-O-glucosides, however, the relevance of such activity is unclear in vivo. Ref.9
Catalytic activity	D-glucosyl-N-acylsphingosine + H2O = D-glucose + N-acylsphingosine. Ref.1
Subcellular location	Cell membrane; Single-pass membrane protein. Note: Not localized to lipid rafts. Ref.9
Tissue specificity	Widely expressed. Highly expressed in brain, heart, skeletal muscle, kidney and placenta and expressed at lower level in liver. Ref.1
Sequence similarities	Belongs to the non-lysosomal glucosylceramidase family.
Biophysicochemical properties	Kinetic parameters: KM=1.7 µM for 3-beta-D-glucosido-lithocholic KM=6.2 µM for 3-beta-D-glucosido-chenodeoxycholic KM=210 µM for beta-D-glucoside
Sequence caution	The sequence AAG44660.1 differs from that shown. Reason: Frameshift at positions 649 and 691.

Ontologies

Keywords
Biological process	Lipid metabolism Sphingolipid metabolism
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane
Molecular function	Glycosidase Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	O-glycoside catabolic process Ref.1 Ref.9 Inferred from direct assay. Source: UniProtKB bile acid metabolic process Ref.1 Ref.9 Inferred from direct assay. Source: UniProtKB glucosylceramide catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Ref.1 Ref.9 Inferred from direct assay. Source: UniProtKB microsome Ref.1 Traceable author statement. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW smooth endoplasmic reticulum Ref.1 Traceable author statement. Source: UniProtKB
Molecular function	beta-glucosidase activity Ref.1 Inferred from direct assay. Source: UniProtKB glucosylceramidase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9HCG7-1)

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: Q9HCG7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     836-927: GLTWEGFQTA...KEAMANLSPE → LLPSGFCLWV...VEVALQRVPS

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9HCG7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-287: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 927	927	Non-lysosomal glucosylceramidase		PRO_0000283758
Regions
	Topological domain	1 – 687	687	Extracellular Potential
	Transmembrane	688 – 708	21	Potential
	Topological domain	709 – 927	219	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	105	1	N-linked (GlcNAc...) Potential
	Glycosylation	245	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 287	287	Missing in isoform 3.		VSP_024383
	Alternative sequence	836 – 927	92	GLTWE…NLSPE → LLPSGFCLWVIVISSTCWEL LEGKDSTASIYPVEVALQRV PS in isoform 2.		VSP_024384
Experimental info
	Sequence conflict	60	1	C → Y in BAB55430. Ref.3
	Sequence conflict	222	1	C → R in BAB55430. Ref.3
	Sequence conflict	482	1	N → K in BAB55430. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 3, 2007. Version 2. Checksum: 1F6879D6E20A2B1D	FASTA	927	104,649
	10 20 30 40 50 60 MGTQDPGNMG TGVPASEQIS CAKEDPQVYC PEETGGTKDV QVTDCKSPED SRPPKETDCC 70 80 90 100 110 120 NPEDSGQLMV SYEGKAMGYQ VPPFGWRICL AHEFTEKRKP FQANNVSLSN MIKHIGMGLR 130 140 150 160 170 180 YLQWWYRKTH VEKKTPFIDM INSVPLRQIY GCPLGGIGGG TITRGWRGQF CRWQLNPGMY 190 200 210 220 230 240 QHRTVIADQF TVCLRREGQT VYQQVLSLER PSVLRSWNWG LCGYFAFYHA LYPRAWTVYQ 250 260 270 280 290 300 LPGQNVTLTC RQITPILPHD YQDSSLPVGV FVWDVENEGD EALDVSIMFS MRNGLGGGDD 310 320 330 340 350 360 APGGLWNEPF CLERSGETVR GLLLHHPTLP NPYTMAVAAR VTAATTVTHI TAFDPDSTGQ 370 380 390 400 410 420 QVWQDLLQDG QLDSPTGQST PTQKGVGIAG AVCVSSKLRP RGQCRLEFSL AWDMPRIMFG 430 440 450 460 470 480 AKGQVHYRRY TRFFGQDGDA APALSHYALC RYAEWEERIS AWQSPVLDDR SLPAWYKSAL 490 500 510 520 530 540 FNELYFLADG GTVWLEVLED SLPEELGRNM CHLRPTLRDY GRFGYLEGQE YRMYNTYDVH 550 560 570 580 590 600 FYASFALIML WPKLELSLQY DMALATLRED LTRRRYLMSG VMAPVKRRNV IPHDIGDPDD 610 620 630 640 650 660 EPWLRVNAYL IHDTADWKDL NLKFVLQVYR DYYLTGDQNF LKDMWPVCLA VMESEMKFDK 670 680 690 700 710 720 DHDGLIENGG YADQTYDGWV TTGPSAYCGG LWLAAVAVMV QMAALCGAQD IQDKFSSILS 730 740 750 760 770 780 RGQEAYERLL WNGRYYNYDS SSRPQSRSVM SDQCAGQWFL KACGLGEGDT EVFPTQHVVR 790 800 810 820 830 840 ALQTIFELNV QAFAGGAMGA VNGMQPHGVP DKSSVQSDEV WVGVVYGLAA TMIQEGLTWE 850 860 870 880 890 900 GFQTAEGCYR TVWERLGLAF QTPEAYCQQR VFRSLAYMRP LSIWAMQLAL QQQQHKKASW 910 920 PKVKQGTGLR TGPMFGPKEA MANLSPE
	Isoform 2. Checksum: 1AF652DAF751EAA5	FASTA	877	98,737
	10 20 30 40 50 60 MGTQDPGNMG TGVPASEQIS CAKEDPQVYC PEETGGTKDV QVTDCKSPED SRPPKETDCC 70 80 90 100 110 120 NPEDSGQLMV SYEGKAMGYQ VPPFGWRICL AHEFTEKRKP FQANNVSLSN MIKHIGMGLR 130 140 150 160 170 180 YLQWWYRKTH VEKKTPFIDM INSVPLRQIY GCPLGGIGGG TITRGWRGQF CRWQLNPGMY 190 200 210 220 230 240 QHRTVIADQF TVCLRREGQT VYQQVLSLER PSVLRSWNWG LCGYFAFYHA LYPRAWTVYQ 250 260 270 280 290 300 LPGQNVTLTC RQITPILPHD YQDSSLPVGV FVWDVENEGD EALDVSIMFS MRNGLGGGDD 310 320 330 340 350 360 APGGLWNEPF CLERSGETVR GLLLHHPTLP NPYTMAVAAR VTAATTVTHI TAFDPDSTGQ 370 380 390 400 410 420 QVWQDLLQDG QLDSPTGQST PTQKGVGIAG AVCVSSKLRP RGQCRLEFSL AWDMPRIMFG 430 440 450 460 470 480 AKGQVHYRRY TRFFGQDGDA APALSHYALC RYAEWEERIS AWQSPVLDDR SLPAWYKSAL 490 500 510 520 530 540 FNELYFLADG GTVWLEVLED SLPEELGRNM CHLRPTLRDY GRFGYLEGQE YRMYNTYDVH 550 560 570 580 590 600 FYASFALIML WPKLELSLQY DMALATLRED LTRRRYLMSG VMAPVKRRNV IPHDIGDPDD 610 620 630 640 650 660 EPWLRVNAYL IHDTADWKDL NLKFVLQVYR DYYLTGDQNF LKDMWPVCLA VMESEMKFDK 670 680 690 700 710 720 DHDGLIENGG YADQTYDGWV TTGPSAYCGG LWLAAVAVMV QMAALCGAQD IQDKFSSILS 730 740 750 760 770 780 RGQEAYERLL WNGRYYNYDS SSRPQSRSVM SDQCAGQWFL KACGLGEGDT EVFPTQHVVR 790 800 810 820 830 840 ALQTIFELNV QAFAGGAMGA VNGMQPHGVP DKSSVQSDEV WVGVVYGLAA TMIQELLPSG 850 860 870 FCLWVIVISS TCWELLEGKD STASIYPVEV ALQRVPS
	Isoform 3. Checksum: C4DA432626E5B7FD	FASTA	640	72,111
	10 20 30 40 50 60 MFSMRNGLGG GDDAPGGLWN EPFCLERSGE TVRGLLLHHP TLPNPYTMAV AARVTAATTV 70 80 90 100 110 120 THITAFDPDS TGQQVWQDLL QDGQLDSPTG QSTPTQKGVG IAGAVCVSSK LRPRGQCRLE 130 140 150 160 170 180 FSLAWDMPRI MFGAKGQVHY RRYTRFFGQD GDAAPALSHY ALCRYAEWEE RISAWQSPVL 190 200 210 220 230 240 DDRSLPAWYK SALFNELYFL ADGGTVWLEV LEDSLPEELG RNMCHLRPTL RDYGRFGYLE 250 260 270 280 290 300 GQEYRMYNTY DVHFYASFAL IMLWPKLELS LQYDMALATL REDLTRRRYL MSGVMAPVKR 310 320 330 340 350 360 RNVIPHDIGD PDDEPWLRVN AYLIHDTADW KDLNLKFVLQ VYRDYYLTGD QNFLKDMWPV 370 380 390 400 410 420 CLAVMESEMK FDKDHDGLIE NGGYADQTYD GWVTTGPSAY CGGLWLAAVA VMVQMAALCG 430 440 450 460 470 480 AQDIQDKFSS ILSRGQEAYE RLLWNGRYYN YDSSSRPQSR SVMSDQCAGQ WFLKACGLGE 490 500 510 520 530 540 GDTEVFPTQH VVRALQTIFE LNVQAFAGGA MGAVNGMQPH GVPDKSSVQS DEVWVGVVYG 550 560 570 580 590 600 LAATMIQEGL TWEGFQTAEG CYRTVWERLG LAFQTPEAYC QQRVFRSLAY MRPLSIWAMQ 610 620 630 640 LALQQQQHKK ASWPKVKQGT GLRTGPMFGP KEAMANLSPE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of human bile acid beta -glucosidase." Matern H., Boermans H., Lottspeich F., Matern S. J. Biol. Chem. 276:37929-37933(2001) [PubMed: 11489889] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 39-46; 619-636 AND 919-927, ENZYME ACTIVITY, TISSUE SPECIFICITY. Tissue: Liver.
[2]	"Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O. DNA Res. 7:273-281(2000) [PubMed: 10997877] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Kidney and Trachea.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Melanoma.
[5]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORM 1). Tissue: Lymph.
[7]	Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z. Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-780 (ISOFORM 3). Tissue: Adrenal gland.
[8]	"Purification and characterization of a microsomal bile acid beta-glucosidase from human liver." Matern H., Heinemann H., Legler G., Matern S. J. Biol. Chem. 272:11261-11267(1997) [PubMed: 9111029] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[9]	"Identification of the non-lysosomal glucosylceramidase as beta-glucosidase 2." Boot R.G., Verhoek M., Donker-Koopman W., Strijland A., van Marle J., Overkleeft H.S., Wennekes T., Aerts J.M.F.G. J. Biol. Chem. 282:1305-1312(2007) [PubMed: 17105727] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ309567 mRNA. Translation: CAC83792.1. AB046825 mRNA. Translation: BAB13431.1. Different initiation. AK027884 mRNA. Translation: BAB55430.1. AL834306 mRNA. Translation: CAD38976.1. AL133410 Genomic DNA. Translation: CAI10981.1. AL133410 Genomic DNA. Translation: CAI10982.1. AL133410 Genomic DNA. Translation: CAI10983.1. BC011363 mRNA. Translation: AAH11363.1. AF258662 mRNA. Translation: AAG44660.1. Frameshift.
IPI	IPI00100668. IPI00645032. IPI00844444.
RefSeq	NP_065995.1.
UniGene	Hs.443134
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q9HCG7.
Proteomic databases
PRIDE	Q9HCG7.
Genome annotation databases
Ensembl	ENST00000378088; ENSP00000367328; ENSG00000070610; Homo sapiens. [Genome view] ENST00000378094; ENSP00000367334; ENSG00000070610; Homo sapiens. [Genome view] ENST00000378103; ENSP00000367343; ENSG00000070610; Homo sapiens. [Genome view]
GeneID	57704.
KEGG	hsa:57704.
UCSC	uc003zxw.1. human.
Organism-specific databases
CTD	57704.
GeneCards	GC09M035726.
HGNC	HGNC:18986. GBA2.
HPA	HPA024026.
MIM	609471. gene.
PharmGKB	PA38773.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9HCG7.
OMA	NYTAYQD.
Enzyme and pathway databases
BRENDA	3.2.1.45. 247.
Gene expression databases
ArrayExpress	Q9HCG7.
Bgee	Q9HCG7.
CleanEx	HS_GBA2.
Genevestigator	Q9HCG7.
Family and domain databases
InterPro	IPR014551. Beta_glucosidase_GBA2-type. IPR006775. Glucosylceramidase. [Graphical view]
Pfam	PF04685. DUF608. 1 hit. [Graphical view]
PIRSF	PIRSF028944. Beta_gluc_GBA2. 1 hit.
ProtoNet	Search...
Other Resources
NextBio	64578.
SOURCE	Search...

Entry information

Entry name

GBA2_HUMAN

Accession

Primary (citable) accession number: Q9HCG7
Secondary accession number(s): Q5TCV6 , Q96A51, Q96LY1, Q96SJ2, Q9H2L8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 3, 2007
Last sequence update:	April 3, 2007
Last modified:	November 3, 2009
This is version 53 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.