3gcx - Revision history

OCA at 07:03, 6 September 2023

OCA — Wed, 06 Sep 2023 07:03:34 GMT

←Older revision		Revision as of 07:03, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='3gcx' size='340' side='right'caption='[[3gcx]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='3gcx' size='340' side='right'caption='[[3gcx]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3gcx]] is a 3 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=3GCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GCX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3gcx]] is a 3 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=3GCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GCX FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 2.7Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style~~=~~'overflow: auto; max-height: 3em;'~~>~~[[3gcw\|3gcw]]~~<~~/div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b~~></td><td class="sblockDat">PCSK9, NARC1, PSEC0052 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), LDLR ([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=3gcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gcx OCA], [https://pdbe.org/3gcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gcx RCSB], [https://www.ebi.ac.uk/pdbsum/3gcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gcx ProSAT]</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=3gcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gcx OCA], [https://pdbe.org/3gcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gcx RCSB], [https://www.ebi.ac.uk/pdbsum/3gcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gcx ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[https://omim.org/entry/603776 603776]]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref> [[https://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Defects in LDLR are the cause of familial hypercholesterolemia (FH) [MIM:[https://omim.org/entry/143890 143890]]; a common autosomal semi-dominant disease that affects about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis).<ref>PMID:3263645</ref> <ref>PMID:2569482</ref> <ref>PMID:3955657</ref> <ref>PMID:8347689</ref> <ref>PMID:2318961</ref> <ref>PMID:1446662</ref> <ref>PMID:1867200</ref> <ref>PMID:8462973</ref> <ref>PMID:8168830</ref> <ref>PMID:2726768</ref> <ref>PMID:1464748</ref> <ref>PMID:7573037</ref> <ref>PMID:7583548</ref> <ref>PMID:7550239</ref> <ref>PMID:7635461</ref> <ref>PMID:7635482</ref> <ref>PMID:7649546</ref> <ref>PMID:7649549</ref> <ref>PMID:8740918</ref> <ref>PMID:8664907</ref> <ref>PMID:9026534</ref> <ref>PMID:9254862</ref> <ref>PMID:9143924</ref> <ref>PMID:9259195</ref> <ref>PMID:9104431</ref> <ref>PMID:9654205</ref> <ref>PMID:9452094</ref> <ref>PMID:9452095</ref> <ref>PMID:9452118</ref> <ref>PMID:10206683</ref> <ref>PMID:10660340</ref> [:]<ref>PMID:9852677</ref> <ref>PMID:9678702</ref> <ref>PMID:10422803</ref> <ref>PMID:10090484</ref> <ref>PMID:10447263</ref> <ref>PMID:10978268</ref> <ref>PMID:10980548</ref> <ref>PMID:10882754</ref> <ref>PMID:11298688</ref> <ref>PMID:17142622</ref> <ref>PMID:19319977</ref> <ref>PMID:22160468</ref>	+	[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[https://omim.org/entry/603776 603776]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref> <ref>PMID:18197702</ref> <ref>PMID:18660751</ref> <ref>PMID:18039658</ref> <ref>PMID:22074827</ref> <ref>PMID:22580899</ref> <ref>PMID:22493497</ref> [[https://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.	+	[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref> <ref>PMID:18197702</ref> <ref>PMID:18660751</ref> <ref>PMID:18039658</ref> <ref>PMID:22074827</ref> <ref>PMID:22580899</ref> <ref>PMID:22493497</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 40:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chen, C]]	+	[[Category: Chen C]]
-	[[Category: Chen~~, J R~~]]	+	[[Category: Chen JR]]
-	[[Category: Horton~~, J D~~]]	+	[[Category: Horton JD]]
-	[[Category: Kwon~~, H J~~]]	+	[[Category: Kwon HJ]]
-	[[Category: Lagace~~, T A~~]]	+	[[Category: Lagace TA]]
-	[[Category: McNutt~~, M C]]~~	+	[[Category: McNutt MC]]
-	~~[[Category: Autocatalytic cleavage]]~~	+
-	~~[[Category: Cholesterol metabolism]]~~	+
-	~~[[Category: Coated pit]]~~	+
-	~~[[Category: Disease mutation]]~~	+
-	~~[[Category: Egf-like domain]]~~	+
-	~~[[Category: Endocytosis]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Host-virus interaction]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Ldl]]~~	+
-	~~[[Category: Ldl receptor]]~~	+
-	~~[[Category: Lipid metabolism]]~~	+
-	~~[[Category: Lipid transport]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Pcsk9]]~~	+
-	~~[[Category: Phosphoprotein]]~~	+
-	~~[[Category: Protease]]~~	+
-	~~[[Category: Protein binding]]~~	+
-	~~[[Category: Receptor]]~~	+
-	~~[[Category: Secreted]]~~	+
-	~~[[Category: Serine protease]]~~	+
-	~~[[Category: Steroid metabolism]]~~	+
-	~~[[Category: Transmembrane]]~~	+
-	~~[[Category: Transport]]~~	+
-	~~[[Category: Zymogen~~]]	+

OCA at 08:01, 9 March 2022

OCA — Wed, 09 Mar 2022 08:01:43 GMT

←Older revision		Revision as of 08:01, 9 March 2022
Line 1:		Line 1:

	==PCSK9:EGFA (pH 7.4)==		==PCSK9:EGFA (pH 7.4)==
-	<StructureSection load='3gcx' size='340' side='right' caption='[[3gcx]], [[Resolution\|resolution]] 2.70Å' scene=''>	+	<StructureSection load='3gcx' size='340' side='right'caption='[[3gcx]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3gcx]] is a 3 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=3GCX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3GCX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3gcx]] is a 3 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=3GCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GCX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3gcw\|3gcw]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3gcw\|3gcw]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PCSK9, NARC1, PSEC0052 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), LDLR ([~~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">PCSK9, NARC1, PSEC0052 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), LDLR ([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=3gcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gcx OCA], [~~http~~://pdbe.org/3gcx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3gcx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3gcx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3gcx ProSAT]</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=3gcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gcx OCA], [https://pdbe.org/3gcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gcx RCSB], [https://www.ebi.ac.uk/pdbsum/3gcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gcx ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[~~http~~://omim.org/entry/603776 603776]]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref> [[~~http~~://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Defects in LDLR are the cause of familial hypercholesterolemia (FH) [MIM:[~~http~~://omim.org/entry/143890 143890]]; a common autosomal semi-dominant disease that affects about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis).<ref>PMID:3263645</ref> <ref>PMID:2569482</ref> <ref>PMID:3955657</ref> <ref>PMID:8347689</ref> <ref>PMID:2318961</ref> <ref>PMID:1446662</ref> <ref>PMID:1867200</ref> <ref>PMID:8462973</ref> <ref>PMID:8168830</ref> <ref>PMID:2726768</ref> <ref>PMID:1464748</ref> <ref>PMID:7573037</ref> <ref>PMID:7583548</ref> <ref>PMID:7550239</ref> <ref>PMID:7635461</ref> <ref>PMID:7635482</ref> <ref>PMID:7649546</ref> <ref>PMID:7649549</ref> <ref>PMID:8740918</ref> <ref>PMID:8664907</ref> <ref>PMID:9026534</ref> <ref>PMID:9254862</ref> <ref>PMID:9143924</ref> <ref>PMID:9259195</ref> <ref>PMID:9104431</ref> <ref>PMID:9654205</ref> <ref>PMID:9452094</ref> <ref>PMID:9452095</ref> <ref>PMID:9452118</ref> <ref>PMID:10206683</ref> <ref>PMID:10660340</ref> [:]<ref>PMID:9852677</ref> <ref>PMID:9678702</ref> <ref>PMID:10422803</ref> <ref>PMID:10090484</ref> <ref>PMID:10447263</ref> <ref>PMID:10978268</ref> <ref>PMID:10980548</ref> <ref>PMID:10882754</ref> <ref>PMID:11298688</ref> <ref>PMID:17142622</ref> <ref>PMID:19319977</ref> <ref>PMID:22160468</ref>	+	[[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[https://omim.org/entry/603776 603776]]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref> [[https://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Defects in LDLR are the cause of familial hypercholesterolemia (FH) [MIM:[https://omim.org/entry/143890 143890]]; a common autosomal semi-dominant disease that affects about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis).<ref>PMID:3263645</ref> <ref>PMID:2569482</ref> <ref>PMID:3955657</ref> <ref>PMID:8347689</ref> <ref>PMID:2318961</ref> <ref>PMID:1446662</ref> <ref>PMID:1867200</ref> <ref>PMID:8462973</ref> <ref>PMID:8168830</ref> <ref>PMID:2726768</ref> <ref>PMID:1464748</ref> <ref>PMID:7573037</ref> <ref>PMID:7583548</ref> <ref>PMID:7550239</ref> <ref>PMID:7635461</ref> <ref>PMID:7635482</ref> <ref>PMID:7649546</ref> <ref>PMID:7649549</ref> <ref>PMID:8740918</ref> <ref>PMID:8664907</ref> <ref>PMID:9026534</ref> <ref>PMID:9254862</ref> <ref>PMID:9143924</ref> <ref>PMID:9259195</ref> <ref>PMID:9104431</ref> <ref>PMID:9654205</ref> <ref>PMID:9452094</ref> <ref>PMID:9452095</ref> <ref>PMID:9452118</ref> <ref>PMID:10206683</ref> <ref>PMID:10660340</ref> [:]<ref>PMID:9852677</ref> <ref>PMID:9678702</ref> <ref>PMID:10422803</ref> <ref>PMID:10090484</ref> <ref>PMID:10447263</ref> <ref>PMID:10978268</ref> <ref>PMID:10980548</ref> <ref>PMID:10882754</ref> <ref>PMID:11298688</ref> <ref>PMID:17142622</ref> <ref>PMID:19319977</ref> <ref>PMID:22160468</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref> <ref>PMID:18197702</ref> <ref>PMID:18660751</ref> <ref>PMID:18039658</ref> <ref>PMID:22074827</ref> <ref>PMID:22580899</ref> <ref>PMID:22493497</ref> [[~~http~~://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.	+	[[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref> <ref>PMID:18197702</ref> <ref>PMID:18660751</ref> <ref>PMID:18039658</ref> <ref>PMID:22074827</ref> <ref>PMID:22580899</ref> <ref>PMID:22493497</ref> [[https://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 41:		Line 41:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Chen, C]]		[[Category: Chen, C]]
	[[Category: Chen, J R]]		[[Category: Chen, J R]]

OCA at 05:19, 7 December 2018

OCA — Fri, 07 Dec 2018 05:19:41 GMT

←Older revision		Revision as of 05:19, 7 December 2018
Line 17:		Line 17:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gc/3gcx_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gc/3gcx_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>

OCA at 05:29, 5 August 2016

OCA — Fri, 05 Aug 2016 05:29:29 GMT

←Older revision		Revision as of 05:29, 5 August 2016
Line 1:		Line 1:
		+
	==PCSK9:EGFA (pH 7.4)==		==PCSK9:EGFA (pH 7.4)==
	<StructureSection load='3gcx' size='340' side='right' caption='[[3gcx]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='3gcx' size='340' side='right' caption='[[3gcx]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3gcx]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GCX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3gcx]] is a 3 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=3GCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GCX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3gcw\|3gcw]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3gcw\|3gcw]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PCSK9, NARC1, PSEC0052 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), LDLR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PCSK9, NARC1, PSEC0052 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), LDLR ([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=3gcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gcx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gcx RCSB], [http://www.ebi.ac.uk/pdbsum/3gcx PDBsum]</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=3gcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gcx OCA], [http://pdbe.org/3gcx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gcx RCSB], [http://www.ebi.ac.uk/pdbsum/3gcx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gcx ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	<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=3gcx ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 30:		Line 31:
	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 3gcx" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 40:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Chen, C]]		[[Category: Chen, C]]
	[[Category: Chen, J R]]		[[Category: Chen, J R]]

OCA at 13:26, 18 December 2014

OCA — Thu, 18 Dec 2014 13:26:03 GMT

←Older revision		Revision as of 13:26, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3gcx~~\| ~~PDB~~=3gcx \| ~~SCENE~~= }}	+	==PCSK9:EGFA (pH 7.4)==
-	===PCSK9:~~EGFA~~ (~~pH 7~~.4)===	+	<StructureSection load='3gcx' size='340' side='right' caption='[[3gcx]], [[Resolution\|resolution]] 2.70Å' scene=''>
-	~~{{ABSTRACT_PUBMED_19224862}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3gcx]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GCX FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3gcw\|3gcw]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PCSK9, NARC1, PSEC0052 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), LDLR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3gcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gcx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gcx RCSB], [http://www.ebi.ac.uk/pdbsum/3gcx PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[http://omim.org/entry/603776 603776]]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref> [[http://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Defects in LDLR are the cause of familial hypercholesterolemia (FH) [MIM:[http://omim.org/entry/143890 143890]]; a common autosomal semi-dominant disease that affects about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis).<ref>PMID:3263645</ref> <ref>PMID:2569482</ref> <ref>PMID:3955657</ref> <ref>PMID:8347689</ref> <ref>PMID:2318961</ref> <ref>PMID:1446662</ref> <ref>PMID:1867200</ref> <ref>PMID:8462973</ref> <ref>PMID:8168830</ref> <ref>PMID:2726768</ref> <ref>PMID:1464748</ref> <ref>PMID:7573037</ref> <ref>PMID:7583548</ref> <ref>PMID:7550239</ref> <ref>PMID:7635461</ref> <ref>PMID:7635482</ref> <ref>PMID:7649546</ref> <ref>PMID:7649549</ref> <ref>PMID:8740918</ref> <ref>PMID:8664907</ref> <ref>PMID:9026534</ref> <ref>PMID:9254862</ref> <ref>PMID:9143924</ref> <ref>PMID:9259195</ref> <ref>PMID:9104431</ref> <ref>PMID:9654205</ref> <ref>PMID:9452094</ref> <ref>PMID:9452095</ref> <ref>PMID:9452118</ref> <ref>PMID:10206683</ref> <ref>PMID:10660340</ref> [:]<ref>PMID:9852677</ref> <ref>PMID:9678702</ref> <ref>PMID:10422803</ref> <ref>PMID:10090484</ref> <ref>PMID:10447263</ref> <ref>PMID:10978268</ref> <ref>PMID:10980548</ref> <ref>PMID:10882754</ref> <ref>PMID:11298688</ref> <ref>PMID:17142622</ref> <ref>PMID:19319977</ref> <ref>PMID:22160468</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref> <ref>PMID:18197702</ref> <ref>PMID:18660751</ref> <ref>PMID:18039658</ref> <ref>PMID:22074827</ref> <ref>PMID:22580899</ref> <ref>PMID:22493497</ref> [[http://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gc/3gcx_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</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].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	PCSK9 is a secreted protein that degrades low density lipoprotein receptors (LDLRs) in liver by binding to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR. It is not known whether PCSK9 causes degradation of LDLRs within the secretory pathway or following secretion and reuptake via endocytosis. Here we show that a mutation in the LDLR EGF-A domain associated with familial hypercholesterolemia, H306Y, results in increased sensitivity to exogenous PCSK9-mediated cellular degradation because of enhanced PCSK9 binding affinity. The crystal structure of the PCSK9-EGF-A(H306Y) complex shows that Tyr-306 forms a hydrogen bond with Asp-374 in PCSK9 at neutral pH, which strengthens the interaction with PCSK9. To block secreted PCSK9 activity, LDLR (H306Y) subfragments were added to the medium of HepG2 cells stably overexpressing wild-type PCSK9 or gain-of-function PCSK9 mutants associated with hypercholesterolemia (D374Y or S127R). These subfragments blocked secreted PCSK9 binding to cell surface LDLRs and resulted in the recovery of LDLR levels to those of control cells. We conclude that PCSK9 acts primarily as a secreted factor to cause LDLR degradation. These studies support the concept that pharmacological inhibition of the PCSK9-LDLR interaction extracellularly will increase hepatic LDLR expression and lower plasma low density lipoprotein levels.

-	~~==Disease==~~	+	Antagonism of secreted PCSK9 increases low density lipoprotein receptor expression in HepG2 cells.,McNutt MC, Kwon HJ, Chen C, Chen JR, Horton JD, Lagace TA J Biol Chem. 2009 Apr 17;284(16):10561-70. Epub 2009 Feb 17. PMID:19224862<ref>PMID:19224862</ref>
-	~~[[http://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Defects in~~ PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[http://omim.org/entry/603776 603776]]. A familial condition characterized by elevated circulating cholesterol contained in either low-density ~~lipoproteins alone or also~~ in ~~very-low-density lipoproteins~~.~~<ref>PMID:12730697</ref> [[http://www~~.~~uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Defects in LDLR are the cause of familial hypercholesterolemia~~ (FH) ~~[MIM~~:~~[http://omim.org/entry/143890 143890]]; a common autosomal semi~~-~~dominant disease that affects about 1 in 500 individuals~~. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis).~~<ref>~~PMID:3263645</ref><ref>PMID:2569482</ref><ref>PMID:3955657</ref><ref>PMID:8347689</ref><ref>PMID:2318961</ref><ref>PMID:1446662</ref><ref>PMID:1867200</ref><ref>PMID:8462973</ref><ref>PMID:8168830</ref><ref>PMID:2726768</ref><ref>PMID:1464748</ref><ref>PMID:7573037</ref><ref>PMID:7583548</ref><ref>PMID:7550239</ref><ref>PMID:7635461</ref><ref>PMID:7635482</ref><ref>PMID:7649546</ref><ref>PMID:7649549</ref><ref>PMID:8740918</ref><ref>PMID:8664907</ref><ref>PMID:9026534</ref><ref>PMID:9254862</ref><ref>PMID:9143924</ref><ref>PMID:9259195</ref><ref>PMID:9104431</ref><ref>PMID:9654205</ref><ref>PMID:9452094</ref><ref>PMID:9452095</ref><ref>PMID:9452118</ref><ref>PMID:10206683</ref><ref>PMID:10660340</ref>[:]<ref>PMID:9852677</ref><ref>PMID:9678702</ref><ref>PMID:10422803</ref><ref>PMID:10090484</ref><ref>PMID:10447263</ref><ref>PMID:10978268</ref><ref>PMID:10980548</ref><ref>PMID:10882754</ref><ref>PMID:11298688</ref><ref>PMID:17142622</ref><ref>PMID:19319977</ref><ref>PMID:~~22160468~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~//www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a ~~non-proteolytic mechanism to enhance the degradation~~ of the ~~hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway~~. ~~May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation~~. ~~Can induce ubiquitination~~ of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<~~ref~~>~~PMID:17461796~~</~~ref~~><ref>PMID:18197702</ref><ref>PMID:18660751</ref><ref>PMID:18039658</ref><ref>PMID:22074827</ref><ref>PMID:22580899</ref><ref>PMID:22493497</ref> [[http://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.	+	</div>

-	==~~About this Structure~~==	+	==See Also==
-	[[~~3gcx~~]] ~~is a 3 chain structure with sequence from~~ [~~http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from~~ [~~http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GCX OCA~~].	+	*[[LDL receptor\|LDL receptor]]
-		+	*[[PCSK9\|PCSK9]]
-	==~~Reference~~==	+	== References ==
-	~~<ref group="xtra">PMID:019224862</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Chen, C.]]	+	[[Category: Chen, C]]
-	[[Category: Chen, J R.]]	+	[[Category: Chen, J R]]
-	[[Category: Horton, J D.]]	+	[[Category: Horton, J D]]
-	[[Category: Kwon, H J.]]	+	[[Category: Kwon, H J]]
-	[[Category: Lagace, T A.]]	+	[[Category: Lagace, T A]]
-	[[Category: McNutt, M C.]]	+	[[Category: McNutt, M C]]
	[[Category: Autocatalytic cleavage]]		[[Category: Autocatalytic cleavage]]
	[[Category: Cholesterol metabolism]]		[[Category: Cholesterol metabolism]]

OCA at 12:13, 24 March 2013

OCA — Sun, 24 Mar 2013 12:13:08 GMT

←Older revision		Revision as of 12:13, 24 March 2013
Line 1:		Line 1:
-	[[Image:3gcx.png\|left\|200px]]
-
	{{STRUCTURE_3gcx\| PDB=3gcx \| SCENE= }}		{{STRUCTURE_3gcx\| PDB=3gcx \| SCENE= }}
-
	===PCSK9:EGFA (pH 7.4)===		===PCSK9:EGFA (pH 7.4)===
		+	{{ABSTRACT_PUBMED_19224862}}

-	~~{{ABSTRACT_PUBMED_19224862}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[http://omim.org/entry/603776 603776]]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref> [[http://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Defects in LDLR are the cause of familial hypercholesterolemia (FH) [MIM:[http://omim.org/entry/143890 143890]]; a common autosomal semi-dominant disease that affects about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis).<ref>PMID:3263645</ref><ref>PMID:2569482</ref><ref>PMID:3955657</ref><ref>PMID:8347689</ref><ref>PMID:2318961</ref><ref>PMID:1446662</ref><ref>PMID:1867200</ref><ref>PMID:8462973</ref><ref>PMID:8168830</ref><ref>PMID:2726768</ref><ref>PMID:1464748</ref><ref>PMID:7573037</ref><ref>PMID:7583548</ref><ref>PMID:7550239</ref><ref>PMID:7635461</ref><ref>PMID:7635482</ref><ref>PMID:7649546</ref><ref>PMID:7649549</ref><ref>PMID:8740918</ref><ref>PMID:8664907</ref><ref>PMID:9026534</ref><ref>PMID:9254862</ref><ref>PMID:9143924</ref><ref>PMID:9259195</ref><ref>PMID:9104431</ref><ref>PMID:9654205</ref><ref>PMID:9452094</ref><ref>PMID:9452095</ref><ref>PMID:9452118</ref><ref>PMID:10206683</ref><ref>PMID:10660340</ref>[:]<ref>PMID:9852677</ref><ref>PMID:9678702</ref><ref>PMID:10422803</ref><ref>PMID:10090484</ref><ref>PMID:10447263</ref><ref>PMID:10978268</ref><ref>PMID:10980548</ref><ref>PMID:10882754</ref><ref>PMID:11298688</ref><ref>PMID:17142622</ref><ref>PMID:19319977</ref><ref>PMID:22160468</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref><ref>PMID:18197702</ref><ref>PMID:18660751</ref><ref>PMID:18039658</ref><ref>PMID:22074827</ref><ref>PMID:22580899</ref><ref>PMID:22493497</ref> [[http://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:019224862</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019224862</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Chen, C.]]		[[Category: Chen, C.]]

OCA: Protected "3gcx" [edit=sysop:move=sysop]

OCA — Wed, 20 Feb 2013 14:29:40 GMT

Protected "3gcx" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:29, 20 February 2013

OCA at 14:29, 20 February 2013

OCA — Wed, 20 Feb 2013 14:29:37 GMT

←Older revision		Revision as of 14:29, 20 February 2013
Line 1:		Line 1:
-	{{Seed}}
	[[Image:3gcx.png\|left\|200px]]		[[Image:3gcx.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3gcx", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3gcx\| PDB=3gcx \| SCENE= }}		{{STRUCTURE_3gcx\| PDB=3gcx \| SCENE= }}

	===PCSK9:EGFA (pH 7.4)===		===PCSK9:EGFA (pH 7.4)===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19224862}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19224862 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_19224862}}		{{ABSTRACT_PUBMED_19224862}}
-
-	==Disease==
-	Known disease associated with this structure: Hypercholesterolemia, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606945 606945]]

	==About this Structure==		==About this Structure==
-	~~3GCX~~ is a 3 ~~chains~~ structure ~~of sequences~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GCX OCA].	+	[[3gcx]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GCX OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19224862~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019224862</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Chen, C.]]		[[Category: Chen, C.]]
Line 34:		Line 19:
	[[Category: Lagace, T A.]]		[[Category: Lagace, T A.]]
	[[Category: McNutt, M C.]]		[[Category: McNutt, M C.]]
-	[[Category: Alternative splicing]]
	[[Category: Autocatalytic cleavage]]		[[Category: Autocatalytic cleavage]]
-	[[Category: Calcium]]
	[[Category: Cholesterol metabolism]]		[[Category: Cholesterol metabolism]]
	[[Category: Coated pit]]		[[Category: Coated pit]]
Line 52:		Line 35:
	[[Category: Pcsk9]]		[[Category: Pcsk9]]
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
-	[[Category: Polymorphism]]
	[[Category: Protease]]		[[Category: Protease]]
	[[Category: Protein binding]]		[[Category: Protein binding]]
Line 62:		Line 44:
	[[Category: Transport]]		[[Category: Transport]]
	[[Category: Zymogen]]		[[Category: Zymogen]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 29 20:55:57 2009''

OCA at 17:55, 29 April 2009

OCA — Wed, 29 Apr 2009 17:55:58 GMT

←Older revision		Revision as of 17:55, 29 April 2009
Line 1:		Line 1:
	{{Seed}}		{{Seed}}
-	[[Image:3gcx.~~jpg~~\|left\|200px]]	+	[[Image:3gcx.png\|left\|200px]]

	<!--		<!--
Line 63:		Line 63:
	[[Category: Zymogen]]		[[Category: Zymogen]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Mar 4 15~~:03:58 2009''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 29 20:55:57 2009''

OCA: New page: {{Seed}} 200px