1ogs - Revision history

OCA at 00:20, 21 November 2024

2024-11-21T00:20:25Z

← Older revision		Revision as of 00:20, 21 November 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ogs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OGS FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ogs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OGS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [https://pdbe.org/1ogs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [https://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ogs ProSAT], [https://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [https://pdbe.org/1ogs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [https://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ogs ProSAT], [https://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[https://www.uniprot.org/uniprot/~~GLCM_HUMAN GLCM_HUMAN~~] ~~Defects in GBA are the cause of~~ Gaucher disease ~~(GD) [MIM:[https://omim.org/entry/230800 230800]~~; ~~also known as glucocerebrosidase deficiency. GD is the most prevalent lysosomal storage~~ disease~~, 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.<ref>PMID:8294033</ref> [:]<ref>PMID:19286695</ref> <ref>PMID:16293621</ref> <ref>PMID:1974409</ref> <ref>PMID:1972019</ref> <ref>PMID:8432537</ref> <ref>PMID:7916532</ref> <ref>PMID:8112750</ref> <ref>PMID:8076951</ref> <ref>PMID:8790604</ref> <ref>PMID:7627184</ref> <ref>PMID:7627192</ref> <ref>PMID:8937765</ref> <ref>PMID:8829654</ref> <ref>PMID:8829663</ref> <ref>PMID:8889591</ref> <ref>PMID:8780099</ref> <ref>PMID:9182788</ref> <ref>PMID:9217217</ref> <ref>PMID:9279145</ref> <ref>PMID:9153297</ref> <ref>PMID:9061570</ref> <ref>PMID:9554454</ref> <ref>PMID:9683600</ref> <ref>PMID:9637431</ref> <ref>PMID:9516376</ref> <ref>PMID:9851895</ref> <ref>PMID:9650766</ref> <ref>PMID:9554746</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:10360404</ref> <ref>PMID:10744424</ref> <ref>PMID:10352942</ref> <ref>PMID:10447266</ref> <ref>PMID:10796875</ref> <ref>PMID:11992489</ref> <ref>PMID:11933202</ref> <ref>PMID:12204005</ref> <ref>PMID:12847165</ref> <ref>PMID:15292921</ref> <ref>PMID:15826241</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 1 ~~(GD1) [MIM:[https://omim.org/entry/230800 230800]~~; ~~also known as adult non~~-~~neuronopathic Gaucher~~ disease. GD1 is characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved.[:]<ref>PMID:19286695</ref> <ref>PMID:8889591</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:12847165</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 2 ~~(GD2) [MIM~~:~~[https~~:~~//omim~~.~~org/entry/230900 230900]; also known as acute neuronopathic Gaucher~~ disease~~. GD2~~ is the most severe form and is universally progressive and fatal. It manifests soon after birth, with death generally occurring before patients reach two years of age.<ref>PMID:19286695</ref> <ref>PMID:9637431</ref> <ref>PMID:9851895</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in ~~GBA are the cause of Gaucher disease type 3 (GD3) [MIM:[https://omim~~.~~org/entry/231000 231000]; also known as subacute neuronopathic Gaucher~~ disease. GD3 has central nervous manifestations.<ref>PMID:19286695</ref> <ref>PMID:8780099</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in ~~GBA are the cause of Gaucher disease type 3C (GD3C) [MIM:[https://omim~~.~~org/entry/231005 231005]; also known as pseudo-Gaucher~~ disease ~~or Gaucher-like disease.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects~~ in ~~GBA are the cause of Gaucher disease perinatal lethal (GDPL) [MIM:[https://omim.org/~~entry~~/608013 608013]~~. It is ~~a 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~~.~~<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Note=~~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.<ref>PMID:~~19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850~~</ref> ~~Defects in GBA contribute to~~ susceptibility to Parkinson disease (PARK) [MIM:[https://omim.org/entry/168600 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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref>		[https://www.uniprot.org/uniprot/GBA1_HUMAN GBA1_HUMAN] Gaucher disease type 3;Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome;Gaucher disease type 1;Hereditary late-onset Parkinson disease;Gaucher disease type 2;Fetal Gaucher disease;NON RARE IN EUROPE: Dementia with Lewy body;NON RARE IN EUROPE: Parkinson disease. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. 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.<ref>PMID:10352942</ref> Disease susceptibility may be associated with variants affecting the gene represented in this entry.
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/~~GLCM_HUMAN GLCM_HUMAN~~]		[https://www.uniprot.org/uniprot/GBA1_HUMAN GBA1_HUMAN] 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: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). 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).<ref>PMID:15916907</ref> <ref>PMID:19279011</ref> <ref>PMID:24211208</ref> <ref>PMID:26724485</ref> <ref>PMID:27378698</ref> <ref>PMID:32144204</ref> <ref>PMID:33361282</ref> <ref>PMID:9201993</ref> <ref>PMID:32144204</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 16:		Line 17:
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/og/1ogs_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/og/1ogs_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/~~initialview01~~.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>

OCA at 03:35, 2 October 2022

2022-10-02T03:35:14Z

← Older revision		Revision as of 03:35, 2 October 2022
Line 3:		Line 3:
	<StructureSection load='1ogs' size='340' side='right'caption='[[1ogs]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1ogs' size='340' side='right'caption='[[1ogs]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ogs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OGS FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ogs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OGS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GBA, GC, GLUC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [https://pdbe.org/1ogs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [https://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ogs ProSAT], [https://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [https://pdbe.org/1ogs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [https://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ogs ProSAT], [https://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/GLCM_HUMAN GLCM_HUMAN]] Defects in GBA are the cause of Gaucher disease (GD) [MIM:[https://omim.org/entry/230800 230800]]; also known as glucocerebrosidase deficiency. GD is the most prevalent lysosomal storage disease, 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.<ref>PMID:8294033</ref> [:]<ref>PMID:19286695</ref> <ref>PMID:16293621</ref> <ref>PMID:1974409</ref> <ref>PMID:1972019</ref> <ref>PMID:8432537</ref> <ref>PMID:7916532</ref> <ref>PMID:8112750</ref> <ref>PMID:8076951</ref> <ref>PMID:8790604</ref> <ref>PMID:7627184</ref> <ref>PMID:7627192</ref> <ref>PMID:8937765</ref> <ref>PMID:8829654</ref> <ref>PMID:8829663</ref> <ref>PMID:8889591</ref> <ref>PMID:8780099</ref> <ref>PMID:9182788</ref> <ref>PMID:9217217</ref> <ref>PMID:9279145</ref> <ref>PMID:9153297</ref> <ref>PMID:9061570</ref> <ref>PMID:9554454</ref> <ref>PMID:9683600</ref> <ref>PMID:9637431</ref> <ref>PMID:9516376</ref> <ref>PMID:9851895</ref> <ref>PMID:9650766</ref> <ref>PMID:9554746</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:10360404</ref> <ref>PMID:10744424</ref> <ref>PMID:10352942</ref> <ref>PMID:10447266</ref> <ref>PMID:10796875</ref> <ref>PMID:11992489</ref> <ref>PMID:11933202</ref> <ref>PMID:12204005</ref> <ref>PMID:12847165</ref> <ref>PMID:15292921</ref> <ref>PMID:15826241</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 1 (GD1) [MIM:[https://omim.org/entry/230800 230800]]; also known as adult non-neuronopathic Gaucher disease. GD1 is characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved.[:]<ref>PMID:19286695</ref> <ref>PMID:8889591</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:12847165</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 2 (GD2) [MIM:[https://omim.org/entry/230900 230900]]; also known as acute neuronopathic Gaucher disease. GD2 is the most severe form and is universally progressive and fatal. It manifests soon after birth, with death generally occurring before patients reach two years of age.<ref>PMID:19286695</ref> <ref>PMID:9637431</ref> <ref>PMID:9851895</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3 (GD3) [MIM:[https://omim.org/entry/231000 231000]]; also known as subacute neuronopathic Gaucher disease. GD3 has central nervous manifestations.<ref>PMID:19286695</ref> <ref>PMID:8780099</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3C (GD3C) [MIM:[https://omim.org/entry/231005 231005]]; also known as pseudo-Gaucher disease or Gaucher-like disease.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease perinatal lethal (GDPL) [MIM:[https://omim.org/entry/608013 608013]]. It is a 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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Note=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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA contribute to susceptibility to Parkinson disease (PARK) [MIM:[https://omim.org/entry/168600 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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref>		[https://www.uniprot.org/uniprot/GLCM_HUMAN GLCM_HUMAN] Defects in GBA are the cause of Gaucher disease (GD) [MIM:[https://omim.org/entry/230800 230800]; also known as glucocerebrosidase deficiency. GD is the most prevalent lysosomal storage disease, 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.<ref>PMID:8294033</ref> [:]<ref>PMID:19286695</ref> <ref>PMID:16293621</ref> <ref>PMID:1974409</ref> <ref>PMID:1972019</ref> <ref>PMID:8432537</ref> <ref>PMID:7916532</ref> <ref>PMID:8112750</ref> <ref>PMID:8076951</ref> <ref>PMID:8790604</ref> <ref>PMID:7627184</ref> <ref>PMID:7627192</ref> <ref>PMID:8937765</ref> <ref>PMID:8829654</ref> <ref>PMID:8829663</ref> <ref>PMID:8889591</ref> <ref>PMID:8780099</ref> <ref>PMID:9182788</ref> <ref>PMID:9217217</ref> <ref>PMID:9279145</ref> <ref>PMID:9153297</ref> <ref>PMID:9061570</ref> <ref>PMID:9554454</ref> <ref>PMID:9683600</ref> <ref>PMID:9637431</ref> <ref>PMID:9516376</ref> <ref>PMID:9851895</ref> <ref>PMID:9650766</ref> <ref>PMID:9554746</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:10360404</ref> <ref>PMID:10744424</ref> <ref>PMID:10352942</ref> <ref>PMID:10447266</ref> <ref>PMID:10796875</ref> <ref>PMID:11992489</ref> <ref>PMID:11933202</ref> <ref>PMID:12204005</ref> <ref>PMID:12847165</ref> <ref>PMID:15292921</ref> <ref>PMID:15826241</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 1 (GD1) [MIM:[https://omim.org/entry/230800 230800]; also known as adult non-neuronopathic Gaucher disease. GD1 is characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved.[:]<ref>PMID:19286695</ref> <ref>PMID:8889591</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:12847165</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 2 (GD2) [MIM:[https://omim.org/entry/230900 230900]; also known as acute neuronopathic Gaucher disease. GD2 is the most severe form and is universally progressive and fatal. It manifests soon after birth, with death generally occurring before patients reach two years of age.<ref>PMID:19286695</ref> <ref>PMID:9637431</ref> <ref>PMID:9851895</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3 (GD3) [MIM:[https://omim.org/entry/231000 231000]; also known as subacute neuronopathic Gaucher disease. GD3 has central nervous manifestations.<ref>PMID:19286695</ref> <ref>PMID:8780099</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3C (GD3C) [MIM:[https://omim.org/entry/231005 231005]; also known as pseudo-Gaucher disease or Gaucher-like disease.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease perinatal lethal (GDPL) [MIM:[https://omim.org/entry/608013 608013]. It is a 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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Note=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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA contribute to susceptibility to Parkinson disease (PARK) [MIM:[https://omim.org/entry/168600 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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref>
			== Function ==
			[https://www.uniprot.org/uniprot/GLCM_HUMAN GLCM_HUMAN]
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 32:		Line 33:
	==See Also==		==See Also==
	*[[Acid-beta-glucosidase\|Acid-beta-glucosidase]]		*[[Acid-beta-glucosidase\|Acid-beta-glucosidase]]
	*[[Acid-~~ÃÂ²~~-glucosidase 3D structures\|Acid-~~ÃÂ²~~-glucosidase 3D structures]]		*[[Acid-beta-glucosidase 3D structures\|Acid-beta-glucosidase 3D structures]]
	*[[Beta-glucosidase\|Beta-glucosidase]]		*[[Beta-glucosidase\|Beta-glucosidase]]
	*[[Cystine\|Cystine]]		*[[Cystine\|Cystine]]
Line 39:		Line 40:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Dvir, H]]		[[Category: Dvir H]]
	[[Category: Futerman~~, A H~~]]		[[Category: Futerman AH]]
	[[Category: Harel, M]]		[[Category: Harel M]]
	[[Category: McCarthy~~, A A~~]]		[[Category: McCarthy AA]]
	[[Category: Silman, I]]		[[Category: Silman I]]
	[[Category: Sussman~~, J L~~]]		[[Category: Sussman JL]]
	[[Category: Toker, L]]		[[Category: Toker L]]
	~~[[Category: Alternative initiation]]~~
	~~[[Category: Cerezyme hydrolase]]~~
	~~[[Category: Disease mutati polymorphism]]~~
	~~[[Category: Gaucher disease]]~~
	~~[[Category: Glucocerebrosidase]]~~
	~~[[Category: Glucosidase]]~~
	~~[[Category: Glycoprote lysosome]]~~
	~~[[Category: Glycosidase]]~~
	~~[[Category: Hydrolase]]~~
	~~[[Category: ISPC, Israel Structural Proteomics Center]]~~
	~~[[Category: Membrane]]~~
	~~[[Category: Pharmaceutical]]~~
	~~[[Category: Sphingolipid metabolism]]~~
	~~[[Category: Structural genomic~~]]

OCA at 09:51, 21 July 2021

2021-07-21T09:51:43Z

← Older revision		Revision as of 09:51, 21 July 2021
Line 3:		Line 3:
	<StructureSection load='1ogs' size='340' side='right'caption='[[1ogs]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1ogs' size='340' side='right'caption='[[1ogs]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ogs]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OGS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1OGS FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ogs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OGS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GBA, GC, GLUC ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GBA, GC, GLUC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [~~http~~://pdbe.org/1ogs PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1ogs ProSAT], [~~http~~://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [https://pdbe.org/1ogs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [https://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ogs ProSAT], [https://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/GLCM_HUMAN GLCM_HUMAN]] Defects in GBA are the cause of Gaucher disease (GD) [MIM:[~~http~~://omim.org/entry/230800 230800]]; also known as glucocerebrosidase deficiency. GD is the most prevalent lysosomal storage disease, 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.<ref>PMID:8294033</ref> [:]<ref>PMID:19286695</ref> <ref>PMID:16293621</ref> <ref>PMID:1974409</ref> <ref>PMID:1972019</ref> <ref>PMID:8432537</ref> <ref>PMID:7916532</ref> <ref>PMID:8112750</ref> <ref>PMID:8076951</ref> <ref>PMID:8790604</ref> <ref>PMID:7627184</ref> <ref>PMID:7627192</ref> <ref>PMID:8937765</ref> <ref>PMID:8829654</ref> <ref>PMID:8829663</ref> <ref>PMID:8889591</ref> <ref>PMID:8780099</ref> <ref>PMID:9182788</ref> <ref>PMID:9217217</ref> <ref>PMID:9279145</ref> <ref>PMID:9153297</ref> <ref>PMID:9061570</ref> <ref>PMID:9554454</ref> <ref>PMID:9683600</ref> <ref>PMID:9637431</ref> <ref>PMID:9516376</ref> <ref>PMID:9851895</ref> <ref>PMID:9650766</ref> <ref>PMID:9554746</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:10360404</ref> <ref>PMID:10744424</ref> <ref>PMID:10352942</ref> <ref>PMID:10447266</ref> <ref>PMID:10796875</ref> <ref>PMID:11992489</ref> <ref>PMID:11933202</ref> <ref>PMID:12204005</ref> <ref>PMID:12847165</ref> <ref>PMID:15292921</ref> <ref>PMID:15826241</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 1 (GD1) [MIM:[~~http~~://omim.org/entry/230800 230800]]; also known as adult non-neuronopathic Gaucher disease. GD1 is characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved.[:]<ref>PMID:19286695</ref> <ref>PMID:8889591</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:12847165</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 2 (GD2) [MIM:[~~http~~://omim.org/entry/230900 230900]]; also known as acute neuronopathic Gaucher disease. GD2 is the most severe form and is universally progressive and fatal. It manifests soon after birth, with death generally occurring before patients reach two years of age.<ref>PMID:19286695</ref> <ref>PMID:9637431</ref> <ref>PMID:9851895</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3 (GD3) [MIM:[~~http~~://omim.org/entry/231000 231000]]; also known as subacute neuronopathic Gaucher disease. GD3 has central nervous manifestations.<ref>PMID:19286695</ref> <ref>PMID:8780099</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3C (GD3C) [MIM:[~~http~~://omim.org/entry/231005 231005]]; also known as pseudo-Gaucher disease or Gaucher-like disease.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease perinatal lethal (GDPL) [MIM:[~~http~~://omim.org/entry/608013 608013]]. It is a 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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Note=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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA contribute to susceptibility to Parkinson disease (PARK) [MIM:[~~http~~://omim.org/entry/168600 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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref>		[[https://www.uniprot.org/uniprot/GLCM_HUMAN GLCM_HUMAN]] Defects in GBA are the cause of Gaucher disease (GD) [MIM:[https://omim.org/entry/230800 230800]]; also known as glucocerebrosidase deficiency. GD is the most prevalent lysosomal storage disease, 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.<ref>PMID:8294033</ref> [:]<ref>PMID:19286695</ref> <ref>PMID:16293621</ref> <ref>PMID:1974409</ref> <ref>PMID:1972019</ref> <ref>PMID:8432537</ref> <ref>PMID:7916532</ref> <ref>PMID:8112750</ref> <ref>PMID:8076951</ref> <ref>PMID:8790604</ref> <ref>PMID:7627184</ref> <ref>PMID:7627192</ref> <ref>PMID:8937765</ref> <ref>PMID:8829654</ref> <ref>PMID:8829663</ref> <ref>PMID:8889591</ref> <ref>PMID:8780099</ref> <ref>PMID:9182788</ref> <ref>PMID:9217217</ref> <ref>PMID:9279145</ref> <ref>PMID:9153297</ref> <ref>PMID:9061570</ref> <ref>PMID:9554454</ref> <ref>PMID:9683600</ref> <ref>PMID:9637431</ref> <ref>PMID:9516376</ref> <ref>PMID:9851895</ref> <ref>PMID:9650766</ref> <ref>PMID:9554746</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:10360404</ref> <ref>PMID:10744424</ref> <ref>PMID:10352942</ref> <ref>PMID:10447266</ref> <ref>PMID:10796875</ref> <ref>PMID:11992489</ref> <ref>PMID:11933202</ref> <ref>PMID:12204005</ref> <ref>PMID:12847165</ref> <ref>PMID:15292921</ref> <ref>PMID:15826241</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 1 (GD1) [MIM:[https://omim.org/entry/230800 230800]]; also known as adult non-neuronopathic Gaucher disease. GD1 is characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved.[:]<ref>PMID:19286695</ref> <ref>PMID:8889591</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:12847165</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 2 (GD2) [MIM:[https://omim.org/entry/230900 230900]]; also known as acute neuronopathic Gaucher disease. GD2 is the most severe form and is universally progressive and fatal. It manifests soon after birth, with death generally occurring before patients reach two years of age.<ref>PMID:19286695</ref> <ref>PMID:9637431</ref> <ref>PMID:9851895</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3 (GD3) [MIM:[https://omim.org/entry/231000 231000]]; also known as subacute neuronopathic Gaucher disease. GD3 has central nervous manifestations.<ref>PMID:19286695</ref> <ref>PMID:8780099</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3C (GD3C) [MIM:[https://omim.org/entry/231005 231005]]; also known as pseudo-Gaucher disease or Gaucher-like disease.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease perinatal lethal (GDPL) [MIM:[https://omim.org/entry/608013 608013]]. It is a 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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Note=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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA contribute to susceptibility to Parkinson disease (PARK) [MIM:[https://omim.org/entry/168600 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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 35:		Line 35:
	*[[Beta-glucosidase\|Beta-glucosidase]]		*[[Beta-glucosidase\|Beta-glucosidase]]
	*[[Cystine\|Cystine]]		*[[Cystine\|Cystine]]
	*[[Disulfide Connectivity of Velaglucerase\|Disulfide Connectivity of Velaglucerase]]
	*[[Human acid-beta-glucosidase covalently bound to conduritol B epoxide\|Human acid-beta-glucosidase covalently bound to conduritol B epoxide]]
	*[[Molecular Playground/Velaglucerase\|Molecular Playground/Velaglucerase]]
	*[[Plant-derived glucocerebrosidase\|Plant-derived glucocerebrosidase]]
	*[[Treatment of Gaucher disease\|Treatment of Gaucher disease]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:08, 16 October 2019

2019-10-16T06:08:18Z

← Older revision		Revision as of 06:08, 16 October 2019
Line 1:		Line 1:

	==human acid-beta-glucosidase==		==human acid-beta-glucosidase==
	<StructureSection load='1ogs' size='340' side='right' caption='[[1ogs]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1ogs' size='340' side='right'caption='[[1ogs]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ogs]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OGS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OGS FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ogs]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OGS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OGS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat">~~<span class='plainlinks'>~~[http://en.~~wikipedia~~.~~org/wiki/Glucosylceramidase Glucosylceramidase], with EC number [http://www~~.~~brenda-enzymes~~.~~info~~/~~php~~/~~result_flat~~.~~php4~~?~~ecno~~=~~3.2.1.45 3.2.1.45~~] ~~</span>~~</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GBA, GC, GLUC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [http://pdbe.org/1ogs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [http://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ogs ProSAT], [http://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [http://pdbe.org/1ogs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [http://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ogs ProSAT], [http://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>
	</table>		</table>
Line 31:		Line 31:

	==See Also==		==See Also==
			*[[Acid-beta-glucosidase\|Acid-beta-glucosidase]]
			*[[Acid-ÃÂ²-glucosidase 3D structures\|Acid-ÃÂ²-glucosidase 3D structures]]
			*[[Beta-glucosidase\|Beta-glucosidase]]
			*[[Cystine\|Cystine]]
	*[[Disulfide Connectivity of Velaglucerase\|Disulfide Connectivity of Velaglucerase]]		*[[Disulfide Connectivity of Velaglucerase\|Disulfide Connectivity of Velaglucerase]]
	*[[Human acid-beta-glucosidase covalently bound to conduritol B epoxide\|Human acid-beta-glucosidase covalently bound to conduritol B epoxide]]		*[[Human acid-beta-glucosidase covalently bound to conduritol B epoxide\|Human acid-beta-glucosidase covalently bound to conduritol B epoxide]]
Line 40:		Line 44:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Glucosylceramidase~~]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Dvir, H]]		[[Category: Dvir, H]]
	[[Category: Futerman, A H]]		[[Category: Futerman, A H]]

OCA at 07:34, 7 February 2018

2018-02-07T07:34:14Z

← Older revision		Revision as of 07:34, 7 February 2018
Line 1:		Line 1:

	==human acid-beta-glucosidase==		==human acid-beta-glucosidase==
	<StructureSection load='1ogs' size='340' side='right' caption='[[1ogs]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1ogs' size='340' side='right' caption='[[1ogs]], [[Resolution\|resolution]] 2.00Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucosylceramidase Glucosylceramidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.45 3.2.1.45] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucosylceramidase Glucosylceramidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.45 3.2.1.45] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [http://pdbe.org/1ogs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [http://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [http://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [http://pdbe.org/1ogs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [http://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ogs ProSAT], [http://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 13:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/og/1ogs_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/og/1ogs_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 30:		Line 31:

	==See Also==		==See Also==
	*[[Acid-beta-glucosidase\|Acid-beta-glucosidase]]
	*[[Cystine\|Cystine]]
	*[[Disulfide Connectivity of Velaglucerase\|Disulfide Connectivity of Velaglucerase]]		*[[Disulfide Connectivity of Velaglucerase\|Disulfide Connectivity of Velaglucerase]]
	*[[Human acid-beta-glucosidase covalently bound to conduritol B epoxide\|Human acid-beta-glucosidase covalently bound to conduritol B epoxide]]		*[[Human acid-beta-glucosidase covalently bound to conduritol B epoxide\|Human acid-beta-glucosidase covalently bound to conduritol B epoxide]]
Line 45:		Line 44:
	[[Category: Futerman, A H]]		[[Category: Futerman, A H]]
	[[Category: Harel, M]]		[[Category: Harel, M]]
	[[Category: ~~Mccarthy~~, A A]]		[[Category: McCarthy, A A]]
	[[Category: Silman, I]]		[[Category: Silman, I]]
	[[Category: Sussman, J L]]		[[Category: Sussman, J L]]
Line 60:		Line 59:
	[[Category: ISPC, Israel Structural Proteomics Center]]		[[Category: ISPC, Israel Structural Proteomics Center]]
	[[Category: Membrane]]		[[Category: Membrane]]
			[[Category: Pharmaceutical]]
	[[Category: Sphingolipid metabolism]]		[[Category: Sphingolipid metabolism]]
	[[Category: Structural genomic]]		[[Category: Structural genomic]]

OCA at 20:52, 8 February 2016

2016-02-08T20:52:54Z

← Older revision		Revision as of 20:52, 8 February 2016
Line 17:		Line 17:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ogs ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 15:17, 10 September 2015

2015-09-10T15:17:26Z

← Older revision		Revision as of 15:17, 10 September 2015
Line 5:		Line 5:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucosylceramidase Glucosylceramidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.45 3.2.1.45] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucosylceramidase Glucosylceramidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.45 3.2.1.45] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [http://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [http://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [http://pdbe.org/1ogs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [http://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [http://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 27:		Line 27:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 1ogs" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 02:04, 25 December 2014

2014-12-25T02:04:39Z

← Older revision		Revision as of 02:04, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ogs]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OGS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OGS FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ogs]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OGS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OGS FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucosylceramidase Glucosylceramidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.45 3.2.1.45] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucosylceramidase Glucosylceramidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.45 3.2.1.45] </span></td></tr>
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [http://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [http://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ogs RCSB], [http://www.ebi.ac.uk/pdbsum/1ogs PDBsum], [http://www.topsan.org/Proteins/ISPC/1ogs TOPSAN]</span></td></tr>
	<table>		</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/GLCM_HUMAN GLCM_HUMAN]] Defects in GBA are the cause of Gaucher disease (GD) [MIM:[http://omim.org/entry/230800 230800]]; also known as glucocerebrosidase deficiency. GD is the most prevalent lysosomal storage disease, 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.<ref>PMID:8294033</ref> [:]<ref>PMID:19286695</ref> <ref>PMID:16293621</ref> <ref>PMID:1974409</ref> <ref>PMID:1972019</ref> <ref>PMID:8432537</ref> <ref>PMID:7916532</ref> <ref>PMID:8112750</ref> <ref>PMID:8076951</ref> <ref>PMID:8790604</ref> <ref>PMID:7627184</ref> <ref>PMID:7627192</ref> <ref>PMID:8937765</ref> <ref>PMID:8829654</ref> <ref>PMID:8829663</ref> <ref>PMID:8889591</ref> <ref>PMID:8780099</ref> <ref>PMID:9182788</ref> <ref>PMID:9217217</ref> <ref>PMID:9279145</ref> <ref>PMID:9153297</ref> <ref>PMID:9061570</ref> <ref>PMID:9554454</ref> <ref>PMID:9683600</ref> <ref>PMID:9637431</ref> <ref>PMID:9516376</ref> <ref>PMID:9851895</ref> <ref>PMID:9650766</ref> <ref>PMID:9554746</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:10360404</ref> <ref>PMID:10744424</ref> <ref>PMID:10352942</ref> <ref>PMID:10447266</ref> <ref>PMID:10796875</ref> <ref>PMID:11992489</ref> <ref>PMID:11933202</ref> <ref>PMID:12204005</ref> <ref>PMID:12847165</ref> <ref>PMID:15292921</ref> <ref>PMID:15826241</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 1 (GD1) [MIM:[http://omim.org/entry/230800 230800]]; also known as adult non-neuronopathic Gaucher disease. GD1 is characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved.[:]<ref>PMID:19286695</ref> <ref>PMID:8889591</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:12847165</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 2 (GD2) [MIM:[http://omim.org/entry/230900 230900]]; also known as acute neuronopathic Gaucher disease. GD2 is the most severe form and is universally progressive and fatal. It manifests soon after birth, with death generally occurring before patients reach two years of age.<ref>PMID:19286695</ref> <ref>PMID:9637431</ref> <ref>PMID:9851895</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3 (GD3) [MIM:[http://omim.org/entry/231000 231000]]; also known as subacute neuronopathic Gaucher disease. GD3 has central nervous manifestations.<ref>PMID:19286695</ref> <ref>PMID:8780099</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3C (GD3C) [MIM:[http://omim.org/entry/231005 231005]]; also known as pseudo-Gaucher disease or Gaucher-like disease.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease perinatal lethal (GDPL) [MIM:[http://omim.org/entry/608013 608013]]. It is a 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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Note=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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA contribute to susceptibility to Parkinson disease (PARK) [MIM:[http://omim.org/entry/168600 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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref>		[[http://www.uniprot.org/uniprot/GLCM_HUMAN GLCM_HUMAN]] Defects in GBA are the cause of Gaucher disease (GD) [MIM:[http://omim.org/entry/230800 230800]]; also known as glucocerebrosidase deficiency. GD is the most prevalent lysosomal storage disease, 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.<ref>PMID:8294033</ref> [:]<ref>PMID:19286695</ref> <ref>PMID:16293621</ref> <ref>PMID:1974409</ref> <ref>PMID:1972019</ref> <ref>PMID:8432537</ref> <ref>PMID:7916532</ref> <ref>PMID:8112750</ref> <ref>PMID:8076951</ref> <ref>PMID:8790604</ref> <ref>PMID:7627184</ref> <ref>PMID:7627192</ref> <ref>PMID:8937765</ref> <ref>PMID:8829654</ref> <ref>PMID:8829663</ref> <ref>PMID:8889591</ref> <ref>PMID:8780099</ref> <ref>PMID:9182788</ref> <ref>PMID:9217217</ref> <ref>PMID:9279145</ref> <ref>PMID:9153297</ref> <ref>PMID:9061570</ref> <ref>PMID:9554454</ref> <ref>PMID:9683600</ref> <ref>PMID:9637431</ref> <ref>PMID:9516376</ref> <ref>PMID:9851895</ref> <ref>PMID:9650766</ref> <ref>PMID:9554746</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:10360404</ref> <ref>PMID:10744424</ref> <ref>PMID:10352942</ref> <ref>PMID:10447266</ref> <ref>PMID:10796875</ref> <ref>PMID:11992489</ref> <ref>PMID:11933202</ref> <ref>PMID:12204005</ref> <ref>PMID:12847165</ref> <ref>PMID:15292921</ref> <ref>PMID:15826241</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 1 (GD1) [MIM:[http://omim.org/entry/230800 230800]]; also known as adult non-neuronopathic Gaucher disease. GD1 is characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved.[:]<ref>PMID:19286695</ref> <ref>PMID:8889591</ref> <ref>PMID:10206680</ref> <ref>PMID:10340647</ref> <ref>PMID:12847165</ref> <ref>PMID:15605411</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 2 (GD2) [MIM:[http://omim.org/entry/230900 230900]]; also known as acute neuronopathic Gaucher disease. GD2 is the most severe form and is universally progressive and fatal. It manifests soon after birth, with death generally occurring before patients reach two years of age.<ref>PMID:19286695</ref> <ref>PMID:9637431</ref> <ref>PMID:9851895</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3 (GD3) [MIM:[http://omim.org/entry/231000 231000]]; also known as subacute neuronopathic Gaucher disease. GD3 has central nervous manifestations.<ref>PMID:19286695</ref> <ref>PMID:8780099</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3C (GD3C) [MIM:[http://omim.org/entry/231005 231005]]; also known as pseudo-Gaucher disease or Gaucher-like disease.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease perinatal lethal (GDPL) [MIM:[http://omim.org/entry/608013 608013]]. It is a 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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Note=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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref> Defects in GBA contribute to susceptibility to Parkinson disease (PARK) [MIM:[http://omim.org/entry/168600 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.<ref>PMID:19286695</ref> <ref>PMID:12847165</ref> <ref>PMID:16148263</ref> <ref>PMID:17620502</ref> <ref>PMID:18332251</ref> <ref>PMID:19846850</ref>
	~~== Function ==~~

	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 43:		Line 41:
	</StructureSection>		</StructureSection>
	[[Category: Glucosylceramidase]]		[[Category: Glucosylceramidase]]
	[[Category: Dvir, H.]]		[[Category: Dvir, H]]
	[[Category: Futerman, A H.]]		[[Category: Futerman, A H]]
	[[Category: Harel, M.]]		[[Category: Harel, M]]
	[[Category: Mccarthy, A A.]]		[[Category: Mccarthy, A A]]
	[[Category: Silman, I.]]		[[Category: Silman, I]]
	[[Category: Sussman, J L.]]		[[Category: Sussman, J L]]
	[[Category: Toker, L.]]		[[Category: Toker, L]]
	[[Category: Alternative initiation]]		[[Category: Alternative initiation]]
	[[Category: Cerezyme hydrolase]]		[[Category: Cerezyme hydrolase]]
Line 59:		Line 57:
	[[Category: Glycosidase]]		[[Category: Glycosidase]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: ISPC]]		[[Category: ISPC, Israel Structural Proteomics Center]]
	~~[[Category:~~ Israel Structural Proteomics Center]]
	[[Category: Membrane]]		[[Category: Membrane]]
	[[Category: Sphingolipid metabolism]]		[[Category: Sphingolipid metabolism]]
	[[Category: Structural genomic]]		[[Category: Structural genomic]]

OCA at 17:10, 29 September 2014

2014-09-29T17:10:01Z

Show changes

OCA at 21:26, 24 March 2013

2013-03-24T21:26:41Z

← Older revision		Revision as of 21:26, 24 March 2013
Line 2:		Line 2:
	===human acid-beta-glucosidase===		===human acid-beta-glucosidase===
	{{ABSTRACT_PUBMED_12792654}}		{{ABSTRACT_PUBMED_12792654}}

			==Disease==
			[[http://www.uniprot.org/uniprot/GLCM_HUMAN GLCM_HUMAN]] Defects in GBA are the cause of Gaucher disease (GD) [MIM:[http://omim.org/entry/230800 230800]]; also known as glucocerebrosidase deficiency. GD is the most prevalent lysosomal storage disease, 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.<ref>PMID:8294033</ref>[:]<ref>PMID:19286695</ref><ref>PMID:16293621</ref><ref>PMID:1974409</ref><ref>PMID:1972019</ref><ref>PMID:8432537</ref><ref>PMID:7916532</ref><ref>PMID:8112750</ref><ref>PMID:8076951</ref><ref>PMID:8790604</ref><ref>PMID:7627184</ref><ref>PMID:7627192</ref><ref>PMID:8937765</ref><ref>PMID:8829654</ref><ref>PMID:8829663</ref><ref>PMID:8889591</ref><ref>PMID:8780099</ref><ref>PMID:9182788</ref><ref>PMID:9217217</ref><ref>PMID:9279145</ref><ref>PMID:9153297</ref><ref>PMID:9061570</ref><ref>PMID:9554454</ref><ref>PMID:9683600</ref><ref>PMID:9637431</ref><ref>PMID:9516376</ref><ref>PMID:9851895</ref><ref>PMID:9650766</ref><ref>PMID:9554746</ref><ref>PMID:10206680</ref><ref>PMID:10340647</ref><ref>PMID:10360404</ref><ref>PMID:10744424</ref><ref>PMID:10352942</ref><ref>PMID:10447266</ref><ref>PMID:10796875</ref><ref>PMID:11992489</ref><ref>PMID:11933202</ref><ref>PMID:12204005</ref><ref>PMID:12847165</ref><ref>PMID:15292921</ref><ref>PMID:15826241</ref><ref>PMID:15605411</ref><ref>PMID:16148263</ref><ref>PMID:17620502</ref><ref>PMID:18332251</ref><ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 1 (GD1) [MIM:[http://omim.org/entry/230800 230800]]; also known as adult non-neuronopathic Gaucher disease. GD1 is characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved.[:]<ref>PMID:19286695</ref><ref>PMID:8889591</ref><ref>PMID:10206680</ref><ref>PMID:10340647</ref><ref>PMID:12847165</ref><ref>PMID:15605411</ref><ref>PMID:16148263</ref><ref>PMID:17620502</ref><ref>PMID:18332251</ref><ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 2 (GD2) [MIM:[http://omim.org/entry/230900 230900]]; also known as acute neuronopathic Gaucher disease. GD2 is the most severe form and is universally progressive and fatal. It manifests soon after birth, with death generally occurring before patients reach two years of age.<ref>PMID:19286695</ref><ref>PMID:9637431</ref><ref>PMID:9851895</ref><ref>PMID:12847165</ref><ref>PMID:16148263</ref><ref>PMID:17620502</ref><ref>PMID:18332251</ref><ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3 (GD3) [MIM:[http://omim.org/entry/231000 231000]]; also known as subacute neuronopathic Gaucher disease. GD3 has central nervous manifestations.<ref>PMID:19286695</ref><ref>PMID:8780099</ref><ref>PMID:12847165</ref><ref>PMID:16148263</ref><ref>PMID:17620502</ref><ref>PMID:18332251</ref><ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease type 3C (GD3C) [MIM:[http://omim.org/entry/231005 231005]]; also known as pseudo-Gaucher disease or Gaucher-like disease.<ref>PMID:19286695</ref><ref>PMID:12847165</ref><ref>PMID:16148263</ref><ref>PMID:17620502</ref><ref>PMID:18332251</ref><ref>PMID:19846850</ref> Defects in GBA are the cause of Gaucher disease perinatal lethal (GDPL) [MIM:[http://omim.org/entry/608013 608013]]. It is a 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.<ref>PMID:19286695</ref><ref>PMID:12847165</ref><ref>PMID:16148263</ref><ref>PMID:17620502</ref><ref>PMID:18332251</ref><ref>PMID:19846850</ref> Note=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.<ref>PMID:19286695</ref><ref>PMID:12847165</ref><ref>PMID:16148263</ref><ref>PMID:17620502</ref><ref>PMID:18332251</ref><ref>PMID:19846850</ref> Defects in GBA contribute to susceptibility to Parkinson disease (PARK) [MIM:[http://omim.org/entry/168600 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.<ref>PMID:19286695</ref><ref>PMID:12847165</ref><ref>PMID:16148263</ref><ref>PMID:17620502</ref><ref>PMID:18332251</ref><ref>PMID:19846850</ref>

	==About this Structure==		==About this Structure==
Line 16:		Line 19:

	==Reference==		==Reference==
	<ref group="xtra">PMID:012792654</ref><references group="xtra"/>		<ref group="xtra">PMID:012792654</ref><references group="xtra"/><references/>
	[[Category: Glucosylceramidase]]		[[Category: Glucosylceramidase]]
	[[Category: Dvir, H.]]		[[Category: Dvir, H.]]