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P04062

- GLCM_HUMAN

UniProt

P04062 - GLCM_HUMAN

Protein

Glucosylceramidase

Gene

GBA

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 189 (01 Oct 2014)
      Sequence version 3 (09 Nov 2004)
      Previous versions | rss
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    Functioni

    Catalytic activityi

    D-glucosyl-N-acylsphingosine + H2O = D-glucose + N-acylsphingosine.

    Enzyme regulationi

    Requires saposin-C and anionic phospholipids for activity.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei274 – 2741Proton donor
    Active sitei379 – 3791Nucleophile

    GO - Molecular functioni

    1. glucosylceramidase activity Source: BHF-UCL
    2. protein binding Source: UniProtKB
    3. receptor binding Source: BHF-UCL

    GO - Biological processi

    1. carbohydrate metabolic process Source: InterPro
    2. cell death Source: UniProtKB-KW
    3. cellular response to tumor necrosis factor Source: BHF-UCL
    4. ceramide biosynthetic process Source: BHF-UCL
    5. glucosylceramide catabolic process Source: BHF-UCL
    6. glycosphingolipid metabolic process Source: Reactome
    7. negative regulation of inflammatory response Source: BHF-UCL
    8. negative regulation of interleukin-6 production Source: BHF-UCL
    9. negative regulation of MAP kinase activity Source: BHF-UCL
    10. positive regulation of protein dephosphorylation Source: BHF-UCL
    11. regulation of water loss via skin Source: Ensembl
    12. response to estrogen Source: Ensembl
    13. response to glucocorticoid Source: Ensembl
    14. response to pH Source: Ensembl
    15. response to testosterone Source: Ensembl
    16. response to thyroid hormone Source: Ensembl
    17. skin morphogenesis Source: Ensembl
    18. small molecule metabolic process Source: Reactome
    19. sphingolipid metabolic process Source: Reactome
    20. sphingosine biosynthetic process Source: BHF-UCL
    21. termination of signal transduction Source: BHF-UCL

    Keywords - Molecular functioni

    Glycosidase, Hydrolase

    Keywords - Biological processi

    Lipid metabolism, Sphingolipid metabolism

    Enzyme and pathway databases

    BRENDAi3.2.1.45. 2681.
    ReactomeiREACT_116105. Glycosphingolipid metabolism.

    Protein family/group databases

    CAZyiGH30. Glycoside Hydrolase Family 30.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Glucosylceramidase (EC:3.2.1.45)
    Alternative name(s):
    Acid beta-glucosidase
    Alglucerase
    Beta-glucocerebrosidase
    Short name:
    Beta-GC
    D-glucosyl-N-acylsphingosine glucohydrolase
    Imiglucerase
    Gene namesi
    Name:GBA
    Synonyms:GC, GLUC
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:4177. GBA.

    Subcellular locationi

    Lysosome membrane 3 Publications; Peripheral membrane protein 3 Publications; Lumenal side 3 Publications
    Note: Interaction with saposin-C promotes membrane association. Targeting to lysosomes occurs through an alternative MPR-independent mechanism via SCARB2.

    GO - Cellular componenti

    1. extracellular vesicular exosome Source: UniProt
    2. lysosomal lumen Source: BHF-UCL
    3. lysosomal membrane Source: UniProtKB

    Keywords - Cellular componenti

    Lysosome, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Gaucher disease (GD) [MIM:230800]: A lysosomal storage disease due to deficient activity of beta-glucocerebrosidase and characterized by accumulation of glucosylceramide in the reticulo-endothelial system. Different clinical forms are recognized depending on the presence (neuronopathic forms) or absence of central nervous system involvement, severity and age of onset.32 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti54 – 541V → L in GD. 1 Publication
    VAR_003255
    Natural varianti55 – 551C → S in GD; neuronopathic and perinatal lethal forms; loss of activity. 2 Publications
    VAR_032394
    Natural varianti63 – 631D → N in GD1; very low activity. 1 Publication
    VAR_032395
    Natural varianti76 – 761F → V in GD. 1 Publication
    VAR_003256
    Natural varianti80 – 801E → K in GD2. 1 Publication
    Corresponds to variant rs1141808 [ dbSNP | Ensembl ].
    VAR_009033
    Natural varianti82 – 821T → I in GD.
    VAR_003257
    Natural varianti85 – 851G → E in GD. 2 Publications
    VAR_003258
    Natural varianti87 – 871R → Q in GD; 20% of normal activity.
    VAR_032197
    Natural varianti87 – 871R → W in GD; mild. 3 Publications
    Corresponds to variant rs1141814 [ dbSNP | Ensembl ].
    VAR_003259
    Natural varianti118 – 1181K → N in GD; mild; 8% of normal activity; increases susceptibility to proteolytic degradation. 1 Publication
    VAR_003260
    Natural varianti129 – 1291A → T in GD. 1 Publication
    VAR_032397
    Natural varianti146 – 1461S → L in GD; type 2. 1 Publication
    VAR_009034
    Natural varianti152 – 1521G → E in GD. 1 Publication
    VAR_003261
    Natural varianti156 – 1561N → D in GD. 1 Publication
    VAR_032398
    Natural varianti158 – 1581I → S in GD1; very low activity. 1 Publication
    VAR_032399
    Natural varianti158 – 1581I → T in GD.
    VAR_003262
    Natural varianti159 – 1591R → Q in GD; type 2; 13% of normal activity. 1 Publication
    VAR_003263
    Natural varianti159 – 1591R → W in GD; severe. 3 Publications
    VAR_003264
    Natural varianti161 – 1611P → L in GD; 16% of normal activity.
    VAR_032198
    Natural varianti161 – 1611P → S in GD; mild.
    VAR_003265
    Natural varianti162 – 1621M → V in GD; loss of activity; increases susceptibility to proteolytic degradation.
    VAR_032199
    Natural varianti166 – 1661D → V in GD; 9% of normal activity; increases susceptibility to proteolytic degradation.
    VAR_032200
    Natural varianti170 – 1701R → C in GD1 and GD2; also found in a patient with Parkinson disease. 3 Publications
    VAR_009035
    Natural varianti170 – 1701R → L in GD. 1 Publication
    VAR_009036
    Natural varianti173 – 1731T → I in GD. 1 Publication
    VAR_032400
    Natural varianti173 – 1731T → P in GD. 2 Publications
    VAR_003266
    Natural varianti175 – 1751A → E in GD. 1 Publication
    VAR_032401
    Natural varianti179 – 1791D → H in GD.
    VAR_003267
    Natural varianti196 – 1961K → Q in GD; severe.
    VAR_003268
    Natural varianti198 – 1981P → L in GD. 1 Publication
    VAR_009037
    Natural varianti198 – 1981P → T in GD. 1 Publication
    VAR_032402
    Natural varianti200 – 2001I → N in GD; 5% of normal activity.
    VAR_032201
    Natural varianti200 – 2001I → S in GD.
    VAR_010059
    Natural varianti201 – 2011H → P in GD. 1 Publication
    VAR_032403
    Natural varianti209 – 2091R → C in GD. 1 Publication
    VAR_032404
    Natural varianti209 – 2091R → P in GD. 1 Publication
    VAR_003269
    Natural varianti213 – 2131L → F in GD; 12% of normal activity.
    VAR_032202
    Natural varianti215 – 2151A → D in GD. 1 Publication
    VAR_003270
    Natural varianti217 – 2171P → S in GD; type 2. 1 Publication
    VAR_003271
    Natural varianti221 – 2211P → L in GD1; very low activity. 1 Publication
    VAR_032405
    Natural varianti221 – 2211P → T in GD. 1 Publication
    VAR_003272
    Natural varianti223 – 2231W → R in GD; gene conversion. 1 Publication
    VAR_003273
    Natural varianti224 – 2241L → F in GD; 4% of normal activity; increases susceptibility to proteolytic degradation.
    VAR_032203
    Natural varianti227 – 2271N → K in GD; gene conversion.
    Corresponds to variant rs381418 [ dbSNP | Ensembl ].
    VAR_003275
    Natural varianti227 – 2271N → S in GD; type 2. 3 Publications
    Corresponds to variant rs364897 [ dbSNP | Ensembl ].
    VAR_003274
    Natural varianti228 – 2281G → V in GD. 1 Publication
    VAR_010060
    Natural varianti229 – 2291A → E in GD; type 2.
    VAR_009038
    Natural varianti229 – 2291A → T in GD. 1 Publication
    VAR_032406
    Natural varianti230 – 2301V → E in GD1; very low activity. 1 Publication
    VAR_032407
    Natural varianti230 – 2301V → G in GD1; gene conversion. 2 Publications
    Corresponds to variant rs381427 [ dbSNP | Ensembl ].
    VAR_003276
    Natural varianti232 – 2321G → E in GD; also found in a patient with Parkinson disease; 7% of normal activity. 1 Publication
    VAR_032204
    Natural varianti234 – 2341G → E in GD; severe. 1 Publication
    VAR_003277
    Natural varianti234 – 2341G → W in GD. 1 Publication
    VAR_009039
    Natural varianti235 – 2351S → P in GD; type 2; gene conversion. 2 Publications
    Corresponds to variant rs1064644 [ dbSNP | Ensembl ].
    VAR_003278
    Natural varianti237 – 2371K → E in GD; severe; loss of activity; increases susceptibility to proteolytic degradation. 1 Publication
    VAR_032205
    Natural varianti241 – 2411G → E in GD.
    VAR_010061
    Natural varianti241 – 2411G → R in GD; type 1 and type 2; gene conversion. 7 Publications
    VAR_003279
    Natural varianti244 – 2441Y → C in GD. 1 Publication
    VAR_010062
    Natural varianti251 – 2511Y → H in GD.
    VAR_003280
    Natural varianti252 – 2521F → I in GD; type 2; gene conversion. 6 Publications
    Corresponds to variant rs381737 [ dbSNP | Ensembl ].
    VAR_003281
    Natural varianti255 – 2551F → Y in GD; mild. 1 Publication
    VAR_003282
    Natural varianti270 – 2701T → R in GD. 1 Publication
    VAR_032408
    Natural varianti276 – 2761S → P in GD.
    VAR_003283
    Natural varianti290 – 2901F → L in GD; perinatal lethal form. 1 Publication
    VAR_032409
    Natural varianti294 – 2941H → Q in GD1; also found in Gaucher disease type 2. 1 Publication
    VAR_009040
    Natural varianti296 – 2961R → Q in GD; type 2; also found in a patient with Parkinson disease. 3 Publications
    VAR_003284
    Natural varianti298 – 2981F → L in GD; type 2; 4% of normal activity. 1 Publication
    VAR_009041
    Natural varianti303 – 3031L → I in GD; 5% of normal activity.
    VAR_032206
    Natural varianti304 – 3041G → D in GD.
    VAR_010063
    Natural varianti305 – 3051P → R in GD; mild.
    VAR_003285
    Natural varianti310 – 3101S → N in GD; less than 5% of normal activity. 1 Publication
    VAR_010064
    Natural varianti324 – 3241R → C in GD; type 1. 3 Publications
    VAR_003286
    Natural varianti324 – 3241R → H in GD; type 2.
    VAR_009042
    Natural varianti328 – 3281P → L in GD; mild.
    VAR_003287
    Natural varianti342 – 3421K → I in GD.
    VAR_003288
    Natural varianti343 – 3431Y → C in GD; type 2; 16% of normal activity; increases susceptibility to proteolytic degradation.
    VAR_009043
    Natural varianti348 – 3481A → V in GD.
    VAR_003289
    Natural varianti350 – 3501H → R in perinatal lethal GD. 1 Publication
    VAR_009044
    Natural varianti351 – 3511W → C in GD; mild.
    VAR_003290
    Natural varianti352 – 3521Y → H in GD. 1 Publication
    VAR_003291
    Natural varianti354 – 3541D → H in GD.
    VAR_003292
    Natural varianti357 – 3571A → D in GD.
    VAR_003293
    Natural varianti362 – 3621T → I in GD; 6% of normal activity.
    VAR_003294
    Natural varianti363 – 3631L → P in GD.
    VAR_003295
    Natural varianti364 – 3641G → R in GD; type 2. 1 Publication
    VAR_003296
    Natural varianti365 – 3651E → K in GD; mild; 42% of normal activity. 1 Publication
    Corresponds to variant rs2230288 [ dbSNP | Ensembl ].
    VAR_003297
    Natural varianti380 – 3801A → T in GD. 2 Publications
    VAR_009045
    Natural varianti381 – 3811C → G in GD; type 2; loss of activity.
    VAR_003298
    Natural varianti388 – 3881E → K in GD; 12% of normal activity.
    VAR_032207
    Natural varianti391 – 3911V → L in GD. 1 Publication
    VAR_010065
    Natural varianti392 – 3921R → G in GD. 1 Publication
    VAR_010066
    Natural varianti392 – 3921R → W in GD; 5% of normal activity.
    VAR_032208
    Natural varianti398 – 3981R → Q in GD; mild. 1 Publication
    VAR_003299
    Natural varianti400 – 4001M → I in GD. 1 Publication
    Corresponds to variant rs149487315 [ dbSNP | Ensembl ].
    VAR_032412
    Natural varianti402 – 4021Y → C in GD; 8% of normal activity; increases susceptibility to proteolytic degradation.
    VAR_032209
    Natural varianti403 – 4031S → T in GD; mild.
    VAR_003300
    Natural varianti405 – 4051S → G in GD. 1 Publication
    VAR_010067
    Natural varianti405 – 4051S → N in GD. 1 Publication
    VAR_009046
    Natural varianti408 – 4081T → M in GD. 2 Publications
    Corresponds to variant rs2230289 [ dbSNP | Ensembl ].
    VAR_003301
    Natural varianti409 – 4091N → S in GD1; common mutation; associated with susceptibility to Parkinson disease; alters interaction with saposin-C; mild. 11 Publications
    Corresponds to variant rs76763715 [ dbSNP | Ensembl ].
    VAR_003302
    Natural varianti410 – 4101L → V in GD; 15% of normal activity; increases susceptibility to proteolytic degradation.
    VAR_032210
    Natural varianti414 – 4141V → L in GD; mild. 1 Publication
    VAR_010068
    Natural varianti416 – 4161G → S in GD; mild. 2 Publications
    VAR_003303
    Natural varianti417 – 4171W → G in GD. 1 Publication
    VAR_003304
    Natural varianti419 – 4191D → A in GD; type 2; also found in a patient with Parkinson disease. 1 Publication
    VAR_003305
    Natural varianti419 – 4191D → H in GD; 4% of normal activity.
    VAR_032211
    Natural varianti419 – 4191D → N in GD. 1 Publication
    VAR_003306
    Natural varianti421 – 4211N → K in GD; 22% of normal activity.
    VAR_032212
    Natural varianti426 – 4261P → L in GD. 1 Publication
    VAR_010069
    Natural varianti428 – 4281G → E in GD; type 2. 1 Publication
    VAR_003307
    Natural varianti429 – 4291G → R in GD; 17% of normal activity.
    VAR_032213
    Natural varianti430 – 4301P → L in GD. 1 Publication
    VAR_003308
    Natural varianti431 – 4311N → I in GD; type 2. 1 Publication
    VAR_003309
    Natural varianti432 – 4321W → R in GD. 1 Publication
    VAR_009047
    Natural varianti433 – 4331V → L in GD; severe; 12% of normal activity. 2 Publications
    VAR_003310
    Natural varianti435 – 4351N → T in GD1; mild. 1 Publication
    VAR_003311
    Natural varianti436 – 4361F → S in GD; 6% of normal activity; alters protein stability and increases susceptibility to proteolytic degradation.
    VAR_032214
    Natural varianti437 – 4371V → F in perinatal lethal GD. 1 Publication
    VAR_009048
    Natural varianti437 – 4371V → L in GD3. 1 Publication
    VAR_010070
    Natural varianti438 – 4381D → N in GD; type 1 and type 2; 14% of normal activity; increases susceptibility to proteolytic degradation. 2 Publications
    VAR_003312
    Natural varianti438 – 4381D → Y in GD. 1 Publication
    VAR_032413
    Natural varianti440 – 4401P → L in GD1. 2 Publications
    VAR_010071
    Natural varianti441 – 4411I → F in GD; type 3. 1 Publication
    VAR_032414
    Natural varianti441 – 4411I → T in GD; mild. 1 Publication
    VAR_010072
    Natural varianti448 – 4481D → H in GD; type 1 and type neuronopathic; at homozygosity it causes GD3C; also found in a patient with Parkinson disease; gene conversion; very low activity; alters protein stability. 9 Publications
    Corresponds to variant rs1064651 [ dbSNP | Ensembl ].
    VAR_003313
    Natural varianti448 – 4481D → V in GD; severe; very low activity; alters protein stability.
    VAR_003314
    Natural varianti450 – 4501F → I in GD.
    VAR_010073
    Natural varianti451 – 4511Y → H in GD. 1 Publication
    VAR_003315
    Natural varianti452 – 4521K → Q in GD. 1 Publication
    VAR_010074
    Natural varianti454 – 4541P → R in GD; type 2.
    VAR_003316
    Natural varianti455 – 4551M → V in GD; loss of activity; increases susceptibility to proteolytic degradation.
    VAR_032215
    Natural varianti456 – 4561F → V in GD.
    VAR_003317
    Natural varianti457 – 4571Y → C in GD. 2 Publications
    VAR_003318
    Natural varianti460 – 4601G → D in GD1; associated with R-490; loss of activity. 1 Publication
    VAR_032415
    Natural varianti464 – 4641K → E in GD; severe.
    VAR_003319
    Natural varianti483 – 4831L → P in GD1 and GD2; common mutation; associated with susceptibility to Parkinson disease; gene conversion; very low activity; alters protein stability. 10 Publications
    VAR_003321
    Natural varianti483 – 4831L → R in GD; severe.
    VAR_003320
    Natural varianti485 – 4851A → P in GD.
    VAR_003322
    Natural varianti490 – 4901H → R in GD; type 1; associated with D-460. 2 Publications
    VAR_032416
    Natural varianti495 – 4951A → P in GD; gene conversion. 1 Publication
    Corresponds to variant rs368060 [ dbSNP | Ensembl ].
    VAR_003323
    Natural varianti500 – 5001L → P in GD; 10% of normal activity; increases susceptibility to proteolytic degradation.
    VAR_032216
    Natural varianti501 – 5011N → K in GD; type 2. 1 Publication
    VAR_009049
    Natural varianti502 – 5021R → C in GD; 37% of normal activity; also found in patients with Parkinson disease. 3 Publications
    VAR_003324
    Natural varianti502 – 5021R → P in GD; loss of activity; increases susceptibility to proteolytic degradation.
    VAR_032217
    Natural varianti513 – 5131D → Y in GD2. 1 Publication
    VAR_009050
    Natural varianti517 – 5171G → S in GD.
    VAR_003326
    Natural varianti530 – 5301T → I in GD3. 1 Publication
    VAR_010075
    Natural varianti535 – 5351R → C in GD; mild. 1 Publication
    VAR_003327
    Natural varianti535 – 5351R → H in GD; mild. 1 Publication
    VAR_003328
    Gaucher disease 1 (GD1) [MIM:230800]: A form of Gaucher disease characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved.5 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti63 – 631D → N in GD1; very low activity. 1 Publication
    VAR_032395
    Natural varianti158 – 1581I → S in GD1; very low activity. 1 Publication
    VAR_032399
    Natural varianti170 – 1701R → C in GD1 and GD2; also found in a patient with Parkinson disease. 3 Publications
    VAR_009035
    Natural varianti221 – 2211P → L in GD1; very low activity. 1 Publication
    VAR_032405
    Natural varianti230 – 2301V → E in GD1; very low activity. 1 Publication
    VAR_032407
    Natural varianti230 – 2301V → G in GD1; gene conversion. 2 Publications
    Corresponds to variant rs381427 [ dbSNP | Ensembl ].
    VAR_003276
    Natural varianti294 – 2941H → Q in GD1; also found in Gaucher disease type 2. 1 Publication
    VAR_009040
    Natural varianti409 – 4091N → S in GD1; common mutation; associated with susceptibility to Parkinson disease; alters interaction with saposin-C; mild. 11 Publications
    Corresponds to variant rs76763715 [ dbSNP | Ensembl ].
    VAR_003302
    Natural varianti435 – 4351N → T in GD1; mild. 1 Publication
    VAR_003311
    Natural varianti440 – 4401P → L in GD1. 2 Publications
    VAR_010071
    Natural varianti460 – 4601G → D in GD1; associated with R-490; loss of activity. 1 Publication
    VAR_032415
    Natural varianti483 – 4831L → P in GD1 and GD2; common mutation; associated with susceptibility to Parkinson disease; gene conversion; very low activity; alters protein stability. 10 Publications
    VAR_003321
    Gaucher disease 2 (GD2) [MIM:230900]: The most severe form of Gaucher disease. It manifests soon after birth, with death generally occurring before patients reach two years of age.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti80 – 801E → K in GD2. 1 Publication
    Corresponds to variant rs1141808 [ dbSNP | Ensembl ].
    VAR_009033
    Natural varianti170 – 1701R → C in GD1 and GD2; also found in a patient with Parkinson disease. 3 Publications
    VAR_009035
    Natural varianti483 – 4831L → P in GD1 and GD2; common mutation; associated with susceptibility to Parkinson disease; gene conversion; very low activity; alters protein stability. 10 Publications
    VAR_003321
    Natural varianti513 – 5131D → Y in GD2. 1 Publication
    VAR_009050
    Gaucher disease 3 (GD3) [MIM:231000]: A subacute form of neuronopathic Gaucher disease. It has later onset and slower progression compared to the acute form of neuronopathic Gaucher disease 2.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti437 – 4371V → L in GD3. 1 Publication
    VAR_010070
    Natural varianti448 – 4481D → H in GD; type 1 and type neuronopathic; at homozygosity it causes GD3C; also found in a patient with Parkinson disease; gene conversion; very low activity; alters protein stability. 9 Publications
    Corresponds to variant rs1064651 [ dbSNP | Ensembl ].
    VAR_003313
    Natural varianti530 – 5301T → I in GD3. 1 Publication
    VAR_010075
    Gaucher disease 3C (GD3C) [MIM:231005]: A variant of subacute neuronopathic Gaucher disease 3 associated with cardiovascular calcifications.
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti448 – 4481D → H in GD; type 1 and type neuronopathic; at homozygosity it causes GD3C; also found in a patient with Parkinson disease; gene conversion; very low activity; alters protein stability. 9 Publications
    Corresponds to variant rs1064651 [ dbSNP | Ensembl ].
    VAR_003313
    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.
    Note: The disease is caused by mutations 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.
    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.3 Publications
    Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry.

    Pharmaceutical usei

    Available under the names Ceredase and Cerezyme (Genzyme). Used to treat Gaucher's disease.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi43 – 431C → S: Loss of activity. 1 Publication
    Mutagenesisi57 – 571C → S: Loss of activity. 1 Publication
    Mutagenesisi62 – 621C → S: Loss of activity. 1 Publication
    Mutagenesisi379 – 3791E → G: Decreases activity 1000-fold. 1 Publication

    Keywords - Diseasei

    Disease mutation, Gaucher disease, Ichthyosis, Neurodegeneration, Parkinson disease, Parkinsonism

    Organism-specific databases

    MIMi168600. phenotype.
    230800. phenotype.
    230900. phenotype.
    231000. phenotype.
    231005. phenotype.
    608013. phenotype.
    Orphaneti1648. Dementia with Lewy body.
    85212. Fetal Gaucher disease.
    2072. Gaucher disease - ophthalmoplegia - cardiovascular calcification.
    77259. Gaucher disease type 1.
    77260. Gaucher disease type 2.
    77261. Gaucher disease type 3.
    319705. Parkinson disease.
    2828. Young adult-onset Parkinsonism.
    PharmGKBiPA28591.

    Protein family/group databases

    Allergomei8244. Hom s Glucocerebrosidase.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3939In isoform Long1 PublicationAdd
    BLAST
    Signal peptidei21 – 3919In isoform Short1 PublicationAdd
    BLAST
    Chaini40 – 536497GlucosylceramidasePRO_0000012177Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi43 ↔ 551 Publication
    Disulfide bondi57 ↔ 621 Publication
    Glycosylationi58 – 581N-linked (GlcNAc...)2 Publications
    Glycosylationi98 – 981N-linked (GlcNAc...)3 Publications
    Glycosylationi185 – 1851N-linked (GlcNAc...)2 Publications
    Glycosylationi309 – 3091N-linked (GlcNAc...)2 Publications
    Glycosylationi501 – 5011N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiP04062.
    PaxDbiP04062.
    PRIDEiP04062.

    PTM databases

    PhosphoSiteiP04062.

    Expressioni

    Gene expression databases

    ArrayExpressiP04062.
    BgeeiP04062.
    CleanExiHS_GBA.
    HS_GC.
    GenevestigatoriP04062.

    Organism-specific databases

    HPAiHPA006667.

    Interactioni

    Subunit structurei

    Interacts with saposin-C. Interacts with SCARB2.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Scarb2O351141EBI-1564609,EBI-1564519From a different organism.

    Protein-protein interaction databases

    BioGridi108899. 11 interactions.
    DIPiDIP-38645N.
    IntActiP04062. 5 interactions.
    MINTiMINT-3004354.
    STRINGi9606.ENSP00000314508.

    Structurei

    Secondary structure

    1
    536
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi49 – 524
    Beta strandi54 – 574
    Beta strandi75 – 828
    Beta strandi88 – 947
    Beta strandi96 – 983
    Beta strandi103 – 11614
    Beta strandi119 – 1235
    Helixi126 – 1338
    Helixi137 – 14812
    Turni150 – 1534
    Beta strandi157 – 1637
    Beta strandi166 – 1705
    Beta strandi177 – 1793
    Helixi190 – 1934
    Helixi196 – 20611
    Beta strandi212 – 2187
    Helixi222 – 2243
    Beta strandi225 – 2273
    Beta strandi229 – 2335
    Beta strandi235 – 2384
    Helixi243 – 26119
    Beta strandi267 – 2715
    Helixi275 – 2795
    Beta strandi284 – 2863
    Helixi292 – 30110
    Helixi303 – 3086
    Turni311 – 3144
    Beta strandi315 – 3239
    Helixi324 – 3263
    Helixi329 – 3357
    Helixi338 – 3414
    Beta strandi346 – 3527
    Helixi354 – 3563
    Helixi359 – 36911
    Beta strandi373 – 3819
    Beta strandi386 – 3883
    Helixi396 – 41116
    Beta strandi414 – 42411
    Beta strandi426 – 4283
    Beta strandi440 – 4445
    Helixi445 – 4473
    Beta strandi449 – 4524
    Helixi454 – 46310
    Beta strandi471 – 4799
    Beta strandi482 – 4898
    Beta strandi495 – 5017
    Beta strandi503 – 5053
    Beta strandi507 – 5137
    Turni514 – 5163
    Beta strandi517 – 5237
    Beta strandi527 – 5337

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1OGSX-ray2.00A/B40-536[»]
    1Y7VX-ray2.40A/B40-536[»]
    2F61X-ray2.50A/B40-536[»]
    2J25X-ray2.90A/B40-536[»]
    2NSXX-ray2.11A/B/C/D40-536[»]
    2NT0X-ray1.79A/B/C/D40-536[»]
    2NT1X-ray2.30A/B/C/D40-536[»]
    2V3DX-ray1.96A/B40-536[»]
    2V3EX-ray2.00A/B40-536[»]
    2V3FX-ray1.95A/B40-536[»]
    2VT0X-ray2.15A/B40-536[»]
    2WCGX-ray2.30A/B40-536[»]
    2WKLX-ray2.70A/B40-536[»]
    2XWDX-ray2.66A/B40-536[»]
    2XWEX-ray2.31A/B40-536[»]
    3GXDX-ray2.50A/B/C/D40-536[»]
    3GXFX-ray2.40A/B/C/D40-536[»]
    3GXIX-ray1.84A/B/C/D40-536[»]
    3GXMX-ray2.20A/B/C/D40-536[»]
    3KE0X-ray2.70A/B40-536[»]
    3KEHX-ray2.80A/B40-536[»]
    3RIKX-ray2.48A/B/C/D40-536[»]
    3RILX-ray2.40A/B/C/D40-536[»]
    ProteinModelPortaliP04062.
    SMRiP04062. Positions 40-536.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP04062.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the glycosyl hydrolase 30 family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiCOG5520.
    HOVERGENiHBG002285.
    InParanoidiP04062.
    KOiK01201.
    OMAiRWAQVVL.
    OrthoDBiEOG76DTRZ.
    PhylomeDBiP04062.
    TreeFamiTF314254.

    Family and domain databases

    Gene3Di2.60.40.1180. 1 hit.
    3.20.20.80. 1 hit.
    InterProiIPR013780. Glyco_hydro_13_b.
    IPR001139. Glyco_hydro_30.
    IPR013781. Glyco_hydro_catalytic_dom.
    IPR017853. Glycoside_hydrolase_SF.
    [Graphical view]
    PANTHERiPTHR11069. PTHR11069. 1 hit.
    PfamiPF02055. Glyco_hydro_30. 1 hit.
    [Graphical view]
    PRINTSiPR00843. GLHYDRLASE30.
    SUPFAMiSSF51445. SSF51445. 1 hit.

    Sequences (5)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 5 isoformsi produced by alternative splicing and alternative initiation. Align

    Isoform Long (identifier: P04062-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MEFSSPSREE CPKPLSRVSI MAGSLTGLLL LQAVSWASGA RPCIPKSFGY    50
    SSVVCVCNAT YCDSFDPPTF PALGTFSRYE STRSGRRMEL SMGPIQANHT 100
    GTGLLLTLQP EQKFQKVKGF GGAMTDAAAL NILALSPPAQ NLLLKSYFSE 150
    EGIGYNIIRV PMASCDFSIR TYTYADTPDD FQLHNFSLPE EDTKLKIPLI 200
    HRALQLAQRP VSLLASPWTS PTWLKTNGAV NGKGSLKGQP GDIYHQTWAR 250
    YFVKFLDAYA EHKLQFWAVT AENEPSAGLL SGYPFQCLGF TPEHQRDFIA 300
    RDLGPTLANS THHNVRLLML DDQRLLLPHW AKVVLTDPEA AKYVHGIAVH 350
    WYLDFLAPAK ATLGETHRLF PNTMLFASEA CVGSKFWEQS VRLGSWDRGM 400
    QYSHSIITNL LYHVVGWTDW NLALNPEGGP NWVRNFVDSP IIVDITKDTF 450
    YKQPMFYHLG HFSKFIPEGS QRVGLVASQK NDLDAVALMH PDGSAVVVVL 500
    NRSSKDVPLT IKDPAVGFLE TISPGYSIHT YLWRRQ 536

    Note: Has a 39 residue signal sequence. The upstream initiation site produces two to three times as much protein as does the downstream initiation codon.

    Length:536
    Mass (Da):59,716
    Last modified:November 9, 2004 - v3
    Checksum:iFA1E15684344A0E6
    GO
    Isoform Short (identifier: P04062-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-20: Missing.

    Note: Has a 19 residue signal sequence.

    Show »
    Length:516
    Mass (Da):57,455
    Checksum:i3905C3D0AA3B1C2B
    GO
    Isoform 3 (identifier: P04062-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-161: Missing.
         422-423: LA → PS
         425-536: Missing.

    Note: Produced by alternative splicing.

    Show »
    Length:263
    Mass (Da):29,897
    Checksum:iBF20F409A5BB4AD0
    GO
    Isoform 4 (identifier: P04062-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-87: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:449
    Mass (Da):50,317
    Checksum:iB9C592918C4B8B78
    GO
    Isoform 5 (identifier: P04062-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         103-151: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:487
    Mass (Da):54,471
    Checksum:iE4D1343DF86B943A
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti176 – 1761D → G in BAH13357. (PubMed:14702039)Curated
    Sequence conflicti227 – 2271N → R in BAA02546. (PubMed:8294033)Curated
    Sequence conflicti470 – 4701S → I AA sequence (PubMed:3456607)Curated
    Sequence conflicti534 – 5341R → H in AAA35873. (PubMed:3864160)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti46 – 461K → E in a patient with Parkinson disease. 1 Publication
    VAR_063066
    Natural varianti54 – 541V → L in GD. 1 Publication
    VAR_003255
    Natural varianti55 – 551C → S in GD; neuronopathic and perinatal lethal forms; loss of activity. 2 Publications
    VAR_032394
    Natural varianti63 – 631D → N in GD1; very low activity. 1 Publication
    VAR_032395
    Natural varianti76 – 761F → V in GD. 1 Publication
    VAR_003256
    Natural varianti80 – 801E → K in GD2. 1 Publication
    Corresponds to variant rs1141808 [ dbSNP | Ensembl ].
    VAR_009033
    Natural varianti82 – 821T → I in GD.
    VAR_003257
    Natural varianti85 – 851G → E in GD. 2 Publications
    VAR_003258
    Natural varianti87 – 871R → Q in GD; 20% of normal activity.
    VAR_032197
    Natural varianti87 – 871R → W in GD; mild. 3 Publications
    Corresponds to variant rs1141814 [ dbSNP | Ensembl ].
    VAR_003259
    Natural varianti92 – 921M → T.
    Corresponds to variant rs3205619 [ dbSNP | Ensembl ].
    VAR_032396
    Natural varianti118 – 1181K → N in GD; mild; 8% of normal activity; increases susceptibility to proteolytic degradation. 1 Publication
    VAR_003260
    Natural varianti129 – 1291A → T in GD. 1 Publication
    VAR_032397
    Natural varianti146 – 1461S → L in GD; type 2. 1 Publication
    VAR_009034
    Natural varianti152 – 1521G → E in GD. 1 Publication
    VAR_003261
    Natural varianti156 – 1561N → D in GD. 1 Publication
    VAR_032398
    Natural varianti158 – 1581I → S in GD1; very low activity. 1 Publication
    VAR_032399
    Natural varianti158 – 1581I → T in GD.
    VAR_003262
    Natural varianti159 – 1591R → Q in GD; type 2; 13% of normal activity. 1 Publication
    VAR_003263
    Natural varianti159 – 1591R → W in GD; severe. 3 Publications
    VAR_003264
    Natural varianti161 – 1611P → L in GD; 16% of normal activity.
    VAR_032198
    Natural varianti161 – 1611P → S in GD; mild.
    VAR_003265
    Natural varianti162 – 1621M → V in GD; loss of activity; increases susceptibility to proteolytic degradation.
    VAR_032199
    Natural varianti166 – 1661D → V in GD; 9% of normal activity; increases susceptibility to proteolytic degradation.
    VAR_032200
    Natural varianti170 – 1701R → C in GD1 and GD2; also found in a patient with Parkinson disease. 3 Publications
    VAR_009035
    Natural varianti170 – 1701R → L in GD. 1 Publication
    VAR_009036
    Natural varianti173 – 1731T → I in GD. 1 Publication
    VAR_032400
    Natural varianti173 – 1731T → P in GD. 2 Publications
    VAR_003266
    Natural varianti175 – 1751A → E in GD. 1 Publication
    VAR_032401
    Natural varianti179 – 1791