UniProtKB - P17439 (GLCM_MOUSE)
Protein
Lysosomal acid glucosylceramidase
Gene
Gba
Organism
Mus musculus (Mouse)
Status
Functioni
Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramide/GlcCer into free ceramide and glucose (PubMed:24211208). Thereby, plays a central role in the degradation of complex lipids and the turnover of cellular membranes (PubMed:27378698). Through the production of ceramides, participates to the PKC-activated salvage pathway of ceramide formation (By similarity). Also plays a role in cholesterol metabolism (PubMed:24211208). May either catalyze the glucosylation of cholesterol, through a transglucosylation reaction that transfers glucose from glucosylceramide to cholesterol (PubMed:24211208). The short chain saturated C8:0-GlcCer and the mono-unsaturated C18:0-GlcCer being the most effective glucose donors for that transglucosylation reaction (By similarity). Under specific conditions, may alternatively catalyze the reverse reaction, transferring glucose from cholesteryl-beta-D-glucoside to ceramide (By similarity). Finally, may also hydrolyze cholesteryl-beta-D-glucoside to produce D-glucose and cholesterol (By similarity).By similarity2 Publications
Catalytic activityi
- EC:3.2.1.451 PublicationThis reaction proceeds in the forward1 Publication direction.
- EC:3.2.1.1041 Publication
Activity regulationi
Inhibited by conduritol B epoxide/CBE.1 Publication
: cholesterol metabolism Pathwayi
This protein is involved in the pathway cholesterol metabolism, which is part of Steroid metabolism.1 PublicationView all proteins of this organism that are known to be involved in the pathway cholesterol metabolism and in Steroid metabolism.
Pathwayi: Sphingolipid metabolism
This protein is involved in Sphingolipid metabolism.1 PublicationView all proteins of this organism that are known to be involved in Sphingolipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 254 | Proton donorBy similarity | 1 | |
Active sitei | 358 | NucleophileBy similarity | 1 |
GO - Molecular functioni
- glucosylceramidase activity Source: UniProtKB
- glucosyltransferase activity Source: UniProtKB
- hydrolase activity Source: MGI
- scavenger receptor binding Source: MGI
- signaling receptor binding Source: BHF-UCL
- steryl-beta-glucosidase activity Source: UniProtKB
GO - Biological processi
- autophagosome organization Source: ParkinsonsUK-UCL
- autophagy Source: UniProtKB
- beta-glucoside catabolic process Source: MGI
- cellular response to starvation Source: ParkinsonsUK-UCL
- cellular response to tumor necrosis factor Source: MGI
- ceramide biosynthetic process Source: MGI
- cholesterol metabolic process Source: UniProtKB
- glucosylceramide catabolic process Source: UniProtKB
- lipid glycosylation Source: UniProtKB
- lysosome organization Source: UniProtKB
- negative regulation of cellular protein metabolic process Source: ParkinsonsUK-UCL
- negative regulation of interleukin-6 production Source: MGI
- negative regulation of MAP kinase activity Source: MGI
- negative regulation of neuron death Source: MGI
- negative regulation of protein complex assembly Source: ParkinsonsUK-UCL
- positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization Source: ParkinsonsUK-UCL
- positive regulation of neuronal action potential Source: MGI
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: ParkinsonsUK-UCL
- positive regulation of protein complex disassembly Source: MGI
- positive regulation of protein dephosphorylation Source: MGI
- positive regulation of protein lipidation Source: MGI
- positive regulation of protein metabolic process Source: MGI
- positive regulation of proteolysis involved in cellular protein catabolic process Source: ParkinsonsUK-UCL
- regulation of cellular protein metabolic process Source: MGI
- regulation of protein metabolic process Source: ParkinsonsUK-UCL
- regulation of TOR signaling Source: UniProtKB
- regulation of water loss via skin Source: MGI
- response to dexamethasone Source: MGI
- response to estrogen Source: MGI
- response to pH Source: MGI
- response to testosterone Source: MGI
- response to thyroid hormone Source: MGI
- skin morphogenesis Source: MGI
- sphingosine biosynthetic process Source: MGI
- termination of signal transduction Source: MGI
Keywordsi
Molecular function | Glycosidase, Glycosyltransferase, Hydrolase, Transferase |
Biological process | Cholesterol metabolism, Lipid metabolism, Sphingolipid metabolism, Steroid metabolism, Sterol metabolism |
Enzyme and pathway databases
BRENDAi | 3.2.1.45 3474 |
Reactomei | R-MMU-1660662 Glycosphingolipid metabolism |
UniPathwayi | UPA00296 |
Protein family/group databases
CAZyi | GH30 Glycoside Hydrolase Family 30 |
Chemistry databases
SwissLipidsi | SLP:000001930 |
Names & Taxonomyi
Protein namesi | Recommended name: Lysosomal acid glucosylceramidaseCurated (EC:3.2.1.452 Publications)Short name: Lysosomal acid GCase1 Publication Alternative name(s): |
Gene namesi | Name:GbaImported |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:95665 Gba |
Subcellular locationi
Lysosome
- Lysosome membrane By similarity; Peripheral membrane protein By similarity; Lumenal side By similarity
Note: Interaction with saposin-C promotes membrane [?]association. Targeting to lysosomes occurs through an alternative MPR-independent mechanism via SCARB2.By similarity
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
Extracellular region or secreted
- extracellular space Source: MGI
Golgi apparatus
- Golgi apparatus Source: UniProtKB
- trans-Golgi network Source: UniProtKB
Lysosome
- lysosomal lumen Source: BHF-UCL
- lysosomal membrane Source: BHF-UCL
- lysosome Source: UniProtKB
Keywords - Cellular componenti
Lysosome, MembranePathology & Biotechi
Disruption phenotypei
Homozygous knockout mice die within 24 hours of birth (PubMed:1594045). They are under weight, respire abnormally and show rapidly progressing cyanosis (PubMed:1594045). Feeding and movement are also decreased in these mice (PubMed:1594045). Macrophages accumulating glucosylceramides in tubular lysosomal deposits are found in liver (in Kupffer cells), bone marrow, spleen and brain (PubMed:1594045). Hematopoietic stem cells conditional knockout of GBA, leads to widespread and organ-specific dysfunction of immune cells. Thymus shows the earliest alteration with features of impaired T-cell maturation, aberrant B-cell recruitment, enhanced antigen presentation, and impaired egress of mature thymocytes (PubMed:22665763).2 Publications
Chemistry databases
ChEMBLi | CHEMBL2278 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | By similarityAdd BLAST | 19 | |
ChainiPRO_0000012178 | 20 – 515 | Lysosomal acid glucosylceramidaseAdd BLAST | 496 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 23 ↔ 35 | By similarity | ||
Disulfide bondi | 37 ↔ 42 | By similarity | ||
Glycosylationi | 38 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 78 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 165 | N-linked (GlcNAc...) (high mannose) asparagine1 Publication | 1 | |
Glycosylationi | 289 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 480 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | P17439 |
jPOSTi | P17439 |
MaxQBi | P17439 |
PaxDbi | P17439 |
PeptideAtlasi | P17439 |
PRIDEi | P17439 |
PTM databases
GlyConnecti | 2339 |
iPTMneti | P17439 |
PhosphoSitePlusi | P17439 |
SwissPalmi | P17439 |
UniCarbKBi | P17439 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000028048 Expressed in 313 organ(s), highest expression level in embryo |
ExpressionAtlasi | P17439 baseline and differential |
Genevisiblei | P17439 MM |
Interactioni
Subunit structurei
Interacts with saposin-C.
Interacts with SCARB2.
Interacts with TCP1.
Interacts with GRN; this interaction prevents aggregation of GBA-SCARB2 complex via interaction with HSPA1A upon stress (PubMed:27789271).
By similarity1 PublicationGO - Molecular functioni
- scavenger receptor binding Source: MGI
- signaling receptor binding Source: BHF-UCL
Protein-protein interaction databases
IntActi | P17439, 4 interactors |
MINTi | P17439 |
STRINGi | 10090.ENSMUSP00000130660 |
Chemistry databases
BindingDBi | P17439 |
Family & Domainsi
Sequence similaritiesi
Belongs to the glycosyl hydrolase 30 family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG2566 Eukaryota COG5520 LUCA |
GeneTreei | ENSGT00390000009464 |
HOGENOMi | HOG000270031 |
InParanoidi | P17439 |
KOi | K01201 |
OMAi | MRHTIGA |
OrthoDBi | 644299at2759 |
PhylomeDBi | P17439 |
TreeFami | TF314254 |
Family and domain databases
Gene3Di | 2.60.40.1180, 1 hit |
InterProi | View protein in InterPro IPR033452 GH30_C IPR001139 Glyco_hydro_30 IPR033453 Glyco_hydro_30_TIM-barrel IPR013780 Glyco_hydro_b IPR017853 Glycoside_hydrolase_SF |
PANTHERi | PTHR11069 PTHR11069, 1 hit |
Pfami | View protein in Pfam PF02055 Glyco_hydro_30, 1 hit PF17189 Glyco_hydro_30C, 1 hit |
PRINTSi | PR00843 GLHYDRLASE30 |
SUPFAMi | SSF51445 SSF51445, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
P17439-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAARLIGFFL FQAVSWAYGA QPCIPKSFGY SSVVCVCNAS YCDSLDPVTL
60 70 80 90 100
PALGTFSRYE STRRGRRMEL SVGAIQANRT GTGLLLTLQP EKKFQKVKGF
110 120 130 140 150
GGAMTDATAL NILALSPPTQ KLLLRSYFST NGIEYNIIRV PMASCDFSIR
160 170 180 190 200
VYTYADTPND FQLSNFSLPE EDTKLKIPLI HQALKMSSRP ISLFASPWTS
210 220 230 240 250
PTWLKTNGRV NGKGSLKGQP GDIFHQTWAN YFVKFLDAYA KYGLRFWAVT
260 270 280 290 300
AENEPTAGLF TGYPFQCLGF TPEHQRDFIS RDLGPALANS SHDVKLLMLD
310 320 330 340 350
DQRLLLPRWA EVVLSDPEAA KYVHGIAVHW YMDFLAPAKA TLGETHRLFP
360 370 380 390 400
NTMLFASEAC VGSKFWEQSV RLGSWDRGMQ YSHSIITNLL YHVTGWTDWN
410 420 430 440 450
LALNPEGGPN WVRNFVDSPI IVDIPKDAFY KQPMFYHLGH FSKFIPEGSQ
460 470 480 490 500
RVALVASEST DLETVALLRP DGSAVVVVLN RSSEDVPLTI SDPDLGFLET
510
VSPGYSIHTY LWRRQ
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A0G2JDK2 | A0A0G2JDK2_MOUSE | Glucosylceramidase | Gba | 388 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M24119 mRNA Translation: AAA37671.1 AY115108 Genomic DNA Translation: AAM66757.1 AK082767 mRNA Translation: BAC38609.1 BC006663 mRNA Translation: AAH06663.1 M89949 Genomic DNA Translation: AAA37665.1 |
CCDSi | CCDS17493.1 |
PIRi | A32931 |
RefSeqi | NP_001070879.1, NM_001077411.2 NP_032120.1, NM_008094.5 |
Genome annotation databases
Ensembli | ENSMUST00000077367; ENSMUSP00000076589; ENSMUSG00000028048 ENSMUST00000167998; ENSMUSP00000130660; ENSMUSG00000028048 |
GeneIDi | 14466 |
KEGGi | mmu:14466 |
UCSCi | uc008pyb.2 mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M24119 mRNA Translation: AAA37671.1 AY115108 Genomic DNA Translation: AAM66757.1 AK082767 mRNA Translation: BAC38609.1 BC006663 mRNA Translation: AAH06663.1 M89949 Genomic DNA Translation: AAA37665.1 |
CCDSi | CCDS17493.1 |
PIRi | A32931 |
RefSeqi | NP_001070879.1, NM_001077411.2 NP_032120.1, NM_008094.5 |
3D structure databases
SMRi | P17439 |
ModBasei | Search... |
Protein-protein interaction databases
IntActi | P17439, 4 interactors |
MINTi | P17439 |
STRINGi | 10090.ENSMUSP00000130660 |
Chemistry databases
BindingDBi | P17439 |
ChEMBLi | CHEMBL2278 |
SwissLipidsi | SLP:000001930 |
Protein family/group databases
CAZyi | GH30 Glycoside Hydrolase Family 30 |
PTM databases
GlyConnecti | 2339 |
iPTMneti | P17439 |
PhosphoSitePlusi | P17439 |
SwissPalmi | P17439 |
UniCarbKBi | P17439 |
Proteomic databases
EPDi | P17439 |
jPOSTi | P17439 |
MaxQBi | P17439 |
PaxDbi | P17439 |
PeptideAtlasi | P17439 |
PRIDEi | P17439 |
Protocols and materials databases
DNASUi | 14466 |
Genome annotation databases
Ensembli | ENSMUST00000077367; ENSMUSP00000076589; ENSMUSG00000028048 ENSMUST00000167998; ENSMUSP00000130660; ENSMUSG00000028048 |
GeneIDi | 14466 |
KEGGi | mmu:14466 |
UCSCi | uc008pyb.2 mouse |
Organism-specific databases
CTDi | 2629 |
MGIi | MGI:95665 Gba |
Phylogenomic databases
eggNOGi | KOG2566 Eukaryota COG5520 LUCA |
GeneTreei | ENSGT00390000009464 |
HOGENOMi | HOG000270031 |
InParanoidi | P17439 |
KOi | K01201 |
OMAi | MRHTIGA |
OrthoDBi | 644299at2759 |
PhylomeDBi | P17439 |
TreeFami | TF314254 |
Enzyme and pathway databases
UniPathwayi | UPA00296 |
BRENDAi | 3.2.1.45 3474 |
Reactomei | R-MMU-1660662 Glycosphingolipid metabolism |
Miscellaneous databases
ChiTaRSi | Gba mouse |
PROi | PR:P17439 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000028048 Expressed in 313 organ(s), highest expression level in embryo |
ExpressionAtlasi | P17439 baseline and differential |
Genevisiblei | P17439 MM |
Family and domain databases
Gene3Di | 2.60.40.1180, 1 hit |
InterProi | View protein in InterPro IPR033452 GH30_C IPR001139 Glyco_hydro_30 IPR033453 Glyco_hydro_30_TIM-barrel IPR013780 Glyco_hydro_b IPR017853 Glycoside_hydrolase_SF |
PANTHERi | PTHR11069 PTHR11069, 1 hit |
Pfami | View protein in Pfam PF02055 Glyco_hydro_30, 1 hit PF17189 Glyco_hydro_30C, 1 hit |
PRINTSi | PR00843 GLHYDRLASE30 |
SUPFAMi | SSF51445 SSF51445, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GLCM_MOUSE | |
Accessioni | P17439Primary (citable) accession number: P17439 Secondary accession number(s): Q78NR7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | August 1, 1990 | |
Last modified: | October 16, 2019 | |
This is version 163 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Direct protein sequencing, Reference proteomeDocuments
- Glycosyl hydrolases
Classification of glycosyl hydrolase families and list of entries - SIMILARITY comments
Index of protein domains and families - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways