GBA
entrez
2629
canonical
uniprot
P04062
canonical
ensembl
ENSG00000177628
resolver
ensp
ENSP00000314508
resolver
ensp
ENSP00000357357
resolver
ensp
ENSP00000397986
resolver
ensp
ENSP00000402577
resolver
ensp
ENSP00000522419
resolver
genesymbol
GBA
resolver
genesymbol
GBA1
resolver
genesymbol_syn
GBA
resolver
genesymbol_syn
GC
resolver
genesymbol_syn
GLUC
resolver
hgnc
HGNC:4177
resolver
uniprot
A0A068F658
resolver
uniprot
A8K796
resolver
uniprot
B7Z5G2
resolver
uniprot
B7Z6S1
resolver
uniprot
B7Z6S9
resolver
uniprot
J3KQG4
resolver
uniprot
J3KQK9
resolver
uniprot
Q16545
resolver
uniprot
Q4VX22
resolver
uniprot
Q6I9R6
resolver
uniprot
Q9UMJ8
resolver
uniprot_entry
A0A068F658_HUMAN
resolver
uniprot_entry
B7Z6S9_HUMAN
resolver
uniprot_entry
GBA1_HUMAN
resolver
uniprot_sec
A8K796
resolver
uniprot_sec
B7Z5G2
resolver
uniprot_sec
B7Z6S1
resolver
uniprot_sec
J3KQG4
resolver
uniprot_sec
J3KQK9
resolver
uniprot_sec
Q16545
resolver
uniprot_sec
Q4VX22
resolver
uniprot_sec
Q6I9R6
resolver
uniprot_sec
Q9UMJ8
resolver
activity_regulation
ACTIVITY REGULATION: Synergistically activated by saposin-A and saposin-C, two saposin peptides produced by proteolytic processing of prosaposin/PSAP (PubMed:9201993). Saposin-C activates GBA1 through its recruitment to membranes (PubMed:10781797, PubMed:9201993). The membrane structure and composition in anionic phospholipids are also important for the activation (PubMed:10781797, PubMed:9201993). Activated by PKC in the salvage pathway of ceramide formation (PubMed:19279011). Inhibited by conduritol B epoxide/CBE (PubMed:24211208, PubMed:26724485). {ECO:0000269|PubMed:10781797, ECO:0000269|PubMed:19279011, ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485, ECO:0000269|PubMed:9201993}.
uniprot
proteins
amino_acid_sequence
MEFSSPSREECPKPLSRVSIMAGSLTGLLLLQAVSWASGARPCIPKSFGYSSVVCVCNATYCDSFDPPTFPALGTFSRYESTRSGRRMELSMGPIQANHTGTGLLLTLQPEQKFQKVKGFGGAMTDAAALNILALSPPAQNLLLKSYFSEEGIGYNIIRVPMASCDFSIRTYTYADTPDDFQLHNFSLPEEDTKLKIPLIHRALQLAQRPVSLLASPWTSPTWLKTNGAVNGKGSLKGQPGDIYHQTWARYFVKFLDAYAEHKLQFWAVTAENEPSAGLLSGYPFQCLGFTPEHQRDFIARDLGPTLANSTHHNVRLLMLDDQRLLLPHWAKVVLTDPEAAKYVHGIAVHWYLDFLAPAKATLGETHRLFPNTMLFASEACVGSKFWEQSVRLGSWDRGMQYSHSIITNLLYHVVGWTDWNLALNPEGGPNWVRNFVDSPIIVDITKDTFYKQPMFYHLGHFSKFIPEGSQRVGLVASQKNDLDAVALMHPDGSAVVVVLNRSSKDVPLTIKDPAVGFLETISPGYSIHTYLWRRQ
uniprot
proteins
disease_involvement
DISEASE: Gaucher disease (GD) [MIM:230800]: An autosomal recessive lysosomal storage disease due to deficient activity of lysosomal beta-glucocerebrosidase, and characterized by accumulation of glucosylceramide in the reticulo-endothelial system. GD is a multisystem disease historically divided into three main subtypes on the basis of the presence of neurologic involvement, age at onset and progression rate: type 1 is the non-neuropathic form, type 2 is the acute neuropathic form with early onset and rapid neurologic deterioration, type 3 is the chronic neuropathic form with slow progression of neurologic features. GD shows a marked phenotypic diversity ranging from adult asymptomatic forms, at the mild end, to perinatal lethal forms at the severe end of the disease spectrum. Formal diagnosis of Gaucher disease is based on the measurement of glucocerebrosidase levels in circulating leukocytes and molecular genetic analysis. {ECO:0000269|PubMed:10352942, ECO:0000269|PubMed:10447266, ECO:0000269|PubMed:10744424, ECO:0000269|PubMed:11933202, ECO:0000269|PubMed:11992489, ECO:0000269|PubMed:15292921, ECO:0000269|PubMed:15826241, ECO:0000269|PubMed:15916907, ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:17620502, ECO:0000269|PubMed:18332251, ECO:0000269|PubMed:1972019, ECO:0000269|PubMed:1974409, ECO:0000269|PubMed:19846850, ECO:0000269|PubMed:7475546, ECO:0000269|PubMed:7627184, ECO:0000269|PubMed:7627192, ECO:0000269|PubMed:8076951, ECO:0000269|PubMed:8294033, ECO:0000269|PubMed:8294487, ECO:0000269|PubMed:8432537, ECO:0000269|PubMed:8829654, ECO:0000269|PubMed:8829663, ECO:0000269|PubMed:8937765, ECO:0000269|PubMed:9061570, ECO:0000269|PubMed:9182788, ECO:0000269|PubMed:9217217, ECO:0000269|PubMed:9516376, ECO:0000269|PubMed:9554454, ECO:0000269|PubMed:9650766}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Gaucher disease 1 (GD1) [MIM:230800]: A form of Gaucher disease, an autosomal recessive lysosomal storage disease due to deficient activity of lysosomal beta-glucocerebrosidase, and characterized by accumulation of glucosylceramide in the reticulo-endothelial system. GD1 is characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved. {ECO:0000269|PubMed:10206680, ECO:0000269|PubMed:10340647, ECO:0000269|PubMed:10360404, ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:11933202, ECO:0000269|PubMed:12204005, ECO:0000269|PubMed:1301953, ECO:0000269|PubMed:1487244, ECO:0000269|PubMed:15605411, ECO:0000269|PubMed:1864608, ECO:0000269|PubMed:1899336, ECO:0000269|PubMed:21098288, ECO:0000269|PubMed:22658918, ECO:0000269|PubMed:2269438, ECO:0000269|PubMed:24022302, ECO:0000269|PubMed:24434810, ECO:0000269|PubMed:24577513, ECO:0000269|PubMed:2508065, ECO:0000269|PubMed:27825739, ECO:0000269|PubMed:32547927, ECO:0000269|PubMed:36776904, ECO:0000269|PubMed:7655857, ECO:0000269|PubMed:7915932, ECO:0000269|PubMed:7916532, ECO:0000269|PubMed:8294487, ECO:0000269|PubMed:8432537, ECO:0000269|PubMed:8547070, ECO:0000269|PubMed:8598642, ECO:0000269|PubMed:8790604, ECO:0000269|PubMed:8829663, ECO:0000269|PubMed:8889591, ECO:0000269|PubMed:9061570, ECO:0000269|PubMed:9153297, ECO:0000269|PubMed:9240741, ECO:0000269|PubMed:9295080, ECO:0000269|PubMed:9554746, ECO:0000269|PubMed:9683600, ECO:0000269|PubMed:9856561, ECO:0000269|Ref.14}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Gaucher disease 2 (GD2) [MIM:230900]: The most severe form of Gaucher disease, an autosomal recessive lysosomal storage disease due to deficient activity of lysosomal beta-glucocerebrosidase, and characterized by accumulation of glucosylceramide in the reticulo-endothelial system. GD2 is an acute neuronopathic form that manifests soon after birth, with death generally occurring before patients reach two years of age. Clinical features include hepatosplenomegaly, developmental regression, growth arrest, and rapidly progressing neurologic deterioration. {ECO:0000269|PubMed:10360404, ECO:0000269|PubMed:10649495, ECO:0000269|PubMed:10679038, ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:11933202, ECO:0000269|PubMed:12204005, ECO:0000269|PubMed:15690354, ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:21098288, ECO:0000269|PubMed:2269438, ECO:0000269|PubMed:24022302, ECO:0000269|PubMed:2464926, ECO:0000269|PubMed:27825739, ECO:0000269|PubMed:32547927, ECO:0000269|PubMed:7627192, ECO:0000269|PubMed:7981693, ECO:0000269|PubMed:8112750, ECO:0000269|PubMed:8294487, ECO:0000269|PubMed:8598642, ECO:0000269|PubMed:9153297, ECO:0000269|PubMed:9240741, ECO:0000269|PubMed:9279145, ECO:0000269|PubMed:9554454, ECO:0000269|PubMed:9554746, ECO:0000269|PubMed:9637431, ECO:0000269|PubMed:9851895, ECO:0000269|PubMed:9856561}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Gaucher disease 3 (GD3) [MIM:231000]: A form of Gaucher disease, an autosomal recessive lysosomal storage disease due to deficient activity of lysosomal beta-glucocerebrosidase, and characterized by accumulation of glucosylceramide in the reticulo-endothelial system. GD3 is a subacute neuronopathic form characterized by later onset and slower progression compared to Gaucher disease 2. {ECO:0000269|PubMed:10360404, ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:11933202, ECO:0000269|PubMed:12204005, ECO:0000269|PubMed:1487244, ECO:0000269|PubMed:24022302, ECO:0000269|PubMed:2508065, ECO:0000269|PubMed:32547927, ECO:0000269|PubMed:34106956, ECO:0000269|PubMed:8294487, ECO:0000269|PubMed:8598642, ECO:0000269|PubMed:8780099, ECO:0000269|PubMed:9683600}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Gaucher disease 3C (GD3C) [MIM:231005]: A variant of subacute neuronopathic Gaucher disease 3 associated with cardiovascular calcifications. {ECO:0000269|PubMed:9040001}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Gaucher disease perinatal lethal (GDPL) [MIM:608013]: Distinct form of Gaucher disease type 2, characterized by fetal onset. Hydrops fetalis, in utero fetal death and neonatal distress are prominent features. When hydrops is absent, neurologic involvement begins in the first week and leads to death within 3 months. Hepatosplenomegaly is a major sign, and is associated with ichthyosis, arthrogryposis, and facial dysmorphism. {ECO:0000269|PubMed:10352942, ECO:0000269|PubMed:11933202}. Note=The disease is caused by variants affecting the gene represented in this entry. Perinatal lethal Gaucher disease is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non-immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders. {ECO:0000269|PubMed:10352942}.; DISEASE: Parkinson disease (PARK) [MIM:168600]: A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features. {ECO:0000269|PubMed:12847165, ECO:0000269|PubMed:16148263, ECO:0000269|PubMed:17620502, ECO:0000269|PubMed:18332251, ECO:0000269|PubMed:19286695, ECO:0000269|PubMed:19846850}. Note=Disease susceptibility may be associated with variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.4.1.-
uniprot
proteins
ec_number
3.2.1.-
uniprot
proteins
ec_number
3.2.1.45
uniprot
proteins
ec_number
3.2.1.46
uniprot
proteins
function
FUNCTION: Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine) into free ceramides (such as N-acylsphing-4-enine) and glucose (PubMed:15916907, PubMed:24211208, PubMed:32144204, PubMed:39395789, PubMed:9201993). Plays a central role in the degradation of complex lipids and the turnover of cellular membranes (PubMed:27378698). Through the production of ceramides, participates in the PKC-activated salvage pathway of ceramide formation (PubMed:19279011). Catalyzes the glucosylation of cholesterol, through a transglucosylation reaction where glucose is transferred from GlcCer to cholesterol (PubMed:24211208, PubMed:26724485, PubMed:32144204). GlcCer containing mono-unsaturated fatty acids (such as beta-D-glucosyl-N-(9Z-octadecenoyl)-sphing-4-enine) are preferred as glucose donors for cholesterol glucosylation when compared with GlcCer containing same chain length of saturated fatty acids (such as beta-D-glucosyl-N-octadecanoyl-sphing-4-enine) (PubMed:24211208). Under specific conditions, may alternatively catalyze the reverse reaction, transferring glucose from cholesteryl 3-beta-D-glucoside to ceramide (Probable) (PubMed:26724485). Can also hydrolyze cholesteryl 3-beta-D-glucoside producing glucose and cholesterol (PubMed:24211208, PubMed:26724485, PubMed:39395789). Catalyzes the hydrolysis of galactosylceramides/GalCers (such as beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine), as well as the transfer of galactose between GalCers and cholesterol in vitro, but with lower activity than with GlcCers (PubMed:32144204). Contrary to GlcCer and GalCer, xylosylceramide/XylCer (such as beta-D-xyosyl-(1<->1')-N-acylsphing-4-enine) is not a good substrate for hydrolysis, however it is a good xylose donor for transxylosylation activity to form cholesteryl 3-beta-D-xyloside (PubMed:33361282). Can also metabolize plant glycosyl phytosterols such as glucosylstigmasterol (PubMed:39395789). {ECO:0000269|PubMed:15916907, ECO:0000269|PubMed:19279011, ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485, ECO:0000269|PubMed:27378698, ECO:0000269|PubMed:32144204, ECO:0000269|PubMed:33361282, ECO:0000269|PubMed:39395789, ECO:0000269|PubMed:9201993, ECO:0000305|PubMed:32144204}.
uniprot
proteins
mass_dalton
59716
uniprot
proteins
mutagenesis
MUTAGEN 43; /note="C->S: Loss of glucosylceramidase activity."; /evidence="ECO:0000269|PubMed:16293621"; MUTAGEN 57; /note="C->S: Loss of glucosylceramidase activity."; /evidence="ECO:0000269|PubMed:16293621"; MUTAGEN 62; /note="C->S: Loss of glucosylceramidase activity."; /evidence="ECO:0000269|PubMed:16293621"; MUTAGEN 379; /note="E->G: 1000-fold decreases of glucosylceramidase activity."; /evidence="ECO:0000269|PubMed:7908905"; MUTAGEN 482; /note="D->E: Loss of glucosylceramidase activity."; /evidence="ECO:0000269|PubMed:8294487"; MUTAGEN 482; /note="D->G: Decreased glucosylceramidase activity."; /evidence="ECO:0000269|PubMed:8294487"; MUTAGEN 482; /note="D->S: Severe decrease of glucosylceramidase activity."; /evidence="ECO:0000269|PubMed:8294487"; MUTAGEN 501; /note="N->D: Loss of glucosylceramidase activity."; /evidence="ECO:0000269|PubMed:8294487"; MUTAGEN 501; /note="N->Q: Loss of glucosylceramidase activity."; /evidence="ECO:0000269|PubMed:8294487
uniprot
proteins
pathway_participation
PATHWAY: Steroid metabolism; cholesterol metabolism. {ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485}.; PATHWAY: Sphingolipid metabolism. {ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485, ECO:0000269|PubMed:9201993}.
uniprot
proteins
protein_family
Glycosyl hydrolase 30 family
uniprot
proteins
pubmed
10206680
uniprot
proteins
pubmed
10340647
uniprot
proteins
pubmed
10352942
uniprot
proteins
pubmed
10360404
uniprot
proteins
pubmed
10447266
uniprot
proteins
pubmed
10527671
uniprot
proteins
pubmed
10649495
uniprot
proteins
pubmed
10679038
uniprot
proteins
pubmed
10744424
uniprot
proteins
pubmed
10781797
uniprot
proteins
pubmed
10796875
uniprot
proteins
pubmed
11903352
uniprot
proteins
pubmed
11933202
uniprot
proteins
pubmed
11992489
uniprot
proteins
pubmed
12204005
uniprot
proteins
pubmed
12694238
uniprot
proteins
pubmed
12754519
uniprot
proteins
pubmed
12792654
uniprot
proteins
pubmed
12847165
uniprot
proteins
pubmed
1301953
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
1487244
uniprot
proteins
pubmed
15292921
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15605411
uniprot
proteins
pubmed
15690354
uniprot
proteins
pubmed
1572652
uniprot
proteins
pubmed
15817452
uniprot
proteins
pubmed
15826241
uniprot
proteins
pubmed
15916907
uniprot
proteins
pubmed
16148263
uniprot
proteins
pubmed
16293621
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17139081
uniprot
proteins
pubmed
17187079
uniprot
proteins
pubmed
17620502
uniprot
proteins
pubmed
17897319
uniprot
proteins
pubmed
18022370
uniprot
proteins
pubmed
18332251
uniprot
proteins
pubmed
1848227
uniprot
proteins
pubmed
1864608
uniprot
proteins
pubmed
1899336
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19279011
uniprot
proteins
pubmed
19286695
uniprot
proteins
pubmed
1972019
uniprot
proteins
pubmed
1974409
uniprot
proteins
pubmed
19846850
uniprot
proteins
pubmed
21098288
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22658918
uniprot
proteins
pubmed
2269438
uniprot
proteins
pubmed
23266198
uniprot
proteins
pubmed
24022302
uniprot
proteins
pubmed
24211208
uniprot
proteins
pubmed
24434810
uniprot
proteins
pubmed
24577513
uniprot
proteins
pubmed
2464926
uniprot
proteins
pubmed
2508065
uniprot
proteins
pubmed
26528954
uniprot
proteins
pubmed
26724485
uniprot
proteins
pubmed
27378698
uniprot
proteins
pubmed
27789271
uniprot
proteins
pubmed
27825739
uniprot
proteins
pubmed
2914709
uniprot
proteins
pubmed
3001061
uniprot
proteins
pubmed
32144204
uniprot
proteins
pubmed
32547927
uniprot
proteins
pubmed
33361282
uniprot
proteins
pubmed
3359914
uniprot
proteins
pubmed
34106956
uniprot
proteins
pubmed
3456607
uniprot
proteins
pubmed
36776904
uniprot
proteins
pubmed
3687939
uniprot
proteins
pubmed
3864160
uniprot
proteins
pubmed
39395789
uniprot
proteins
pubmed
6091633
uniprot
proteins
pubmed
7475546
uniprot
proteins
pubmed
7627184
uniprot
proteins
pubmed
7627192
uniprot
proteins
pubmed
7655857
uniprot
proteins
pubmed
7908905
uniprot
proteins
pubmed
7915932
uniprot
proteins
pubmed
7916532
uniprot
proteins
pubmed
7981693
uniprot
proteins
pubmed
8076951
uniprot
proteins
pubmed
8112750
uniprot
proteins
pubmed
8118460
uniprot
proteins
pubmed
8294033
uniprot
proteins
pubmed
8294487
uniprot
proteins
pubmed
8432537
uniprot
proteins
pubmed
8547070
uniprot
proteins
pubmed
8598642
uniprot
proteins
pubmed
8780099
uniprot
proteins
pubmed
8790604
uniprot
proteins
pubmed
8829654
uniprot
proteins
pubmed
8829663
uniprot
proteins
pubmed
8889578
uniprot
proteins
pubmed
8889591
uniprot
proteins
pubmed
8937765
uniprot
proteins
pubmed
9040001
uniprot
proteins
pubmed
9061570
uniprot
proteins
pubmed
9153297
uniprot
proteins
pubmed
9182788
uniprot
proteins
pubmed
9201993
uniprot
proteins
pubmed
9217217
uniprot
proteins
pubmed
9240741
uniprot
proteins
pubmed
9279145
uniprot
proteins
pubmed
9295080
uniprot
proteins
pubmed
9331372
uniprot
proteins
pubmed
9516376
uniprot
proteins
pubmed
9554454
uniprot
proteins
pubmed
9554746
uniprot
proteins
pubmed
9637431
uniprot
proteins
pubmed
9650766
uniprot
proteins
pubmed
9683600
uniprot
proteins
pubmed
9851895
uniprot
proteins
pubmed
9856561
uniprot
proteins
sequence_length
536
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:17187079, ECO:0000269|PubMed:17897319, ECO:0000269|PubMed:18022370}; Peripheral membrane protein {ECO:0000269|PubMed:10781797, ECO:0000269|PubMed:18022370, ECO:0000269|PubMed:1848227}; Lumenal side {ECO:0000269|PubMed:18022370}. Note=Interaction with saposin-C promotes membrane association (PubMed:10781797). Targeting to lysosomes occurs through an alternative MPR-independent mechanism via SCARB2 (PubMed:18022370). {ECO:0000269|PubMed:10781797, ECO:0000269|PubMed:18022370}.
uniprot
proteins