3bps - Revision history

OCA at 08:49, 30 October 2024

2024-10-30T08:49:57Z

← Older revision		Revision as of 08:49, 30 October 2024
Line 17:		Line 17:
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bp/3bps_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bp/3bps_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 12:12, 30 August 2023

2023-08-30T12:12:00Z

← Older revision		Revision as of 12:12, 30 August 2023
Line 3:		Line 3:
	<StructureSection load='3bps' size='340' side='right'caption='[[3bps]], [[Resolution\|resolution]] 2.41Å' scene=''>		<StructureSection load='3bps' size='340' side='right'caption='[[3bps]], [[Resolution\|resolution]] 2.41Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3bps]] 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=3BPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BPS FirstGlance]. <br>		<table><tr><td colspan='2'>[[3bps]] 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=3BPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BPS 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]] 2.41Å</td></tr>
	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~PCSK9, NARC1 ([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='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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bps OCA], [https://pdbe.org/3bps PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bps RCSB], [https://www.ebi.ac.uk/pdbsum/3bps PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bps 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=3bps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bps OCA], [https://pdbe.org/3bps PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bps RCSB], [https://www.ebi.ac.uk/pdbsum/3bps PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bps 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 39:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Kwon~~, H J]]~~		[[Category: Kwon HJ]]
	~~[[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: Hydrolase-lipid transport complex]]~~
	~~[[Category: Ldl receptor]]~~
	~~[[Category: Lipid metabolism]]~~
	~~[[Category: Lipid transport]]~~
	~~[[Category: Membrane]]~~
	~~[[Category: Pcsk9]]~~
	~~[[Category: Phosphoprotein]]~~
	~~[[Category: Protease]]~~
	~~[[Category: Secreted]]~~
	~~[[Category: Serine protease]]~~
	~~[[Category: Steroid metabolism]]~~
	~~[[Category: Transmembrane]]~~
	~~[[Category: Transport]]~~
	~~[[Category: Zymogen~~]]

OCA at 08:21, 19 January 2022

2022-01-19T08:21:30Z

← Older revision		Revision as of 08:21, 19 January 2022
Line 1:		Line 1:

	==PCSK9:EGF-A complex==		==PCSK9:EGF-A complex==
	<StructureSection load='3bps' size='340' side='right' caption='[[3bps]], [[Resolution\|resolution]] 2.41Å' scene=''>		<StructureSection load='3bps' size='340' side='right'caption='[[3bps]], [[Resolution\|resolution]] 2.41Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3bps]] 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=3BPS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3BPS FirstGlance]. <br>		<table><tr><td colspan='2'>[[3bps]] 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=3BPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BPS 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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PCSK9, NARC1 ([~~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 ([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=3bps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bps OCA], [~~http~~://pdbe.org/3bps PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3bps RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3bps PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3bps 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=3bps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bps OCA], [https://pdbe.org/3bps PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bps RCSB], [https://www.ebi.ac.uk/pdbsum/3bps PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bps 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 40:		Line 40:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Kwon, H J]]		[[Category: Kwon, H J]]
	[[Category: Autocatalytic cleavage]]		[[Category: Autocatalytic cleavage]]

OCA at 07:56, 31 October 2018

2018-10-31T07:56:47Z

← Older revision		Revision as of 07:56, 31 October 2018
Line 1:		Line 1:

	==PCSK9:EGF-A complex==		==PCSK9:EGF-A complex==
	<StructureSection load='3bps' size='340' side='right' caption='[[3bps]], [[Resolution\|resolution]] 2.41Å' scene=''>		<StructureSection load='3bps' size='340' side='right' caption='[[3bps]], [[Resolution\|resolution]] 2.41Å' scene=''>
Line 5:		Line 6:
	</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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PCSK9, NARC1 ([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 ([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=3bps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bps OCA], [http://pdbe.org/3bps PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bps RCSB], [http://www.ebi.ac.uk/pdbsum/3bps 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=3bps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bps OCA], [http://pdbe.org/3bps PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bps RCSB], [http://www.ebi.ac.uk/pdbsum/3bps PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3bps ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bp/3bps_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bp/3bps_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 16:47, 8 February 2016

2016-02-08T16:47:48Z

← Older revision		Revision as of 16:47, 8 February 2016
Line 2:		Line 2:
	<StructureSection load='3bps' size='340' side='right' caption='[[3bps]], [[Resolution\|resolution]] 2.41Å' scene=''>		<StructureSection load='3bps' size='340' side='right' caption='[[3bps]], [[Resolution\|resolution]] 2.41Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3bps]] 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=3BPS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BPS FirstGlance]. <br>		<table><tr><td colspan='2'>[[3bps]] 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=3BPS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BPS 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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PCSK9, NARC1 ([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 ([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=3bps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bps OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bps RCSB], [http://www.ebi.ac.uk/pdbsum/3bps 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=3bps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bps OCA], [http://pdbe.org/3bps PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bps RCSB], [http://www.ebi.ac.uk/pdbsum/3bps PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 19:
	<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=3bps ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 29:
	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 3bps" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 37:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Kwon, H J]]		[[Category: Kwon, H J]]
	[[Category: Autocatalytic cleavage]]		[[Category: Autocatalytic cleavage]]

OCA at 08:10, 20 January 2015

2015-01-20T08:10:02Z

← Older revision		Revision as of 08:10, 20 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3bps]] 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=3BPS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BPS FirstGlance]. <br>		<table><tr><td colspan='2'>[[3bps]] 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=3BPS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BPS FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene><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><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PCSK9, NARC1 ([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 ([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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bps OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bps RCSB], [http://www.ebi.ac.uk/pdbsum/3bps 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=3bps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bps OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bps RCSB], [http://www.ebi.ac.uk/pdbsum/3bps PDBsum]</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>		[[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>
Line 38:		Line 38:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Kwon, H J.]]		[[Category: Kwon, H J]]
	[[Category: Autocatalytic cleavage]]		[[Category: Autocatalytic cleavage]]
	[[Category: Cholesterol metabolism]]		[[Category: Cholesterol metabolism]]

OCA at 21:11, 2 October 2014

2014-10-02T21:11:26Z

← Older revision		Revision as of 21:11, 2 October 2014
Line 1:		Line 1:
	~~{{STRUCTURE_3bps~~\| ~~PDB~~=3bps \| ~~SCENE~~= }}		==PCSK9:EGF-A complex==
	===~~PCSK9~~:~~EGF~~-~~A complex~~===		<StructureSection load='3bps' size='340' side='right' caption='[[3bps]], [[Resolution\|resolution]] 2.41Å' scene=''>
	~~{{ABSTRACT_PUBMED_18250299}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[3bps]] 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=3BPS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BPS FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene><br>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PCSK9, NARC1 ([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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bps OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bps RCSB], [http://www.ebi.ac.uk/pdbsum/3bps 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/bp/3bps_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 ==
			Proprotein convertase subtilisin/kexin type 9 (PCSK9) posttranslationally regulates hepatic low-density lipoprotein receptors (LDLRs) by binding to LDLRs on the cell surface, leading to their degradation. The binding site of PCSK9 has been localized to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR. Here, we describe the crystal structure of a complex between PCSK9 and the EGF-A domain of the LDLR. The binding site for the LDLR EGF-A domain resides on the surface of PCSK9's subtilisin-like catalytic domain containing Asp-374, a residue for which a gain-of-function mutation (Asp-374-Tyr) increases the affinity of PCSK9 toward LDLR and increases plasma LDL-cholesterol (LDL-C) levels in humans. The binding surface on PCSK9 is distant from its catalytic site, and the EGF-A domain makes no contact with either the C-terminal domain or the prodomain. Point mutations in PCSK9 that altered key residues contributing to EGF-A binding (Arg-194 and Phe-379) greatly diminished binding to the LDLR's extracellular domain. The structure of PCSK9 in complex with the LDLR EGF-A domain defines potential therapeutic target sites for blocking agents that could interfere with this interaction in vivo, thereby increasing LDLR function and reducing plasma LDL-C levels.

	~~==Disease==~~		Molecular basis for LDL receptor recognition by PCSK9.,Kwon HJ, Lagace TA, McNutt MC, Horton JD, Deisenhofer J Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):1820-5. Epub 2008 Feb 4. PMID:18250299<ref>PMID:18250299</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==
	[[~~3bps~~]] ~~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=3BPS OCA~~].		*[[LDL receptor\|LDL receptor]]
			*[[PCSK9\|PCSK9]]
	==~~Reference~~==		== References ==
	~~<ref group="xtra">PMID:018250299</ref>~~<references ~~group="xtra"~~/><~~references~~/>		<references/>
			__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Kwon, H J.]]		[[Category: Kwon, H J.]]

OCA at 18:38, 24 March 2013

2013-03-24T18:38:16Z

← Older revision		Revision as of 18:38, 24 March 2013
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	~~[[Image:3bps.png\|left\|200px]]~~

	{{STRUCTURE_3bps\| PDB=3bps \| SCENE= }}		{{STRUCTURE_3bps\| PDB=3bps \| SCENE= }}
			===PCSK9:EGF-A complex===
			{{ABSTRACT_PUBMED_18250299}}

	===PCSK9:~~EGF~~-~~A complex===~~		==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>

	~~{{ABSTRACT_PUBMED_18250299}}~~		==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==
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	==Reference==		==Reference==
	<ref group="xtra">PMID:018250299</ref><references group="xtra"/>		<ref group="xtra">PMID:018250299</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Kwon, H J.]]		[[Category: Kwon, H J.]]

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

2013-01-07T20:52:38Z

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

← Older revision	Revision as of 20:52, 7 January 2013
(No difference)

OCA at 20:52, 7 January 2013

2013-01-07T20:52:36Z

← Older revision		Revision as of 20:52, 7 January 2013
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	~~{{Seed}}~~
	[[Image:3bps.png\|left\|200px]]		[[Image:3bps.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_3bps", 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_3bps\| PDB=3bps \| SCENE= }}		{{STRUCTURE_3bps\| PDB=3bps \| SCENE= }}

	===PCSK9:EGF-A complex===		===PCSK9:EGF-A complex===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_18250299}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 18250299 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_18250299}}		{{ABSTRACT_PUBMED_18250299}}

	~~==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==
	~~3BPS~~ 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=3BPS OCA].		[[3bps]] 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=3BPS OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~18250299~~</ref><references group="xtra"/>		<ref group="xtra">PMID:018250299</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Kwon, H J.]]		[[Category: Kwon, H J.]]
	~~[[Category: Alternative splicing]]~~
	[[Category: Autocatalytic cleavage]]		[[Category: Autocatalytic cleavage]]
	~~[[Category: Calcium]]~~
	[[Category: Cholesterol metabolism]]		[[Category: Cholesterol metabolism]]
	[[Category: Coated pit]]		[[Category: Coated pit]]
Line 40:		Line 23:
	[[Category: Host-virus interaction]]		[[Category: Host-virus interaction]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Hydrolase/lipid transport complex]]		[[Category: Hydrolase-lipid transport complex]]
	[[Category: Ldl receptor]]		[[Category: Ldl receptor]]
	[[Category: Lipid metabolism]]		[[Category: Lipid metabolism]]
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	[[Category: Pcsk9]]		[[Category: Pcsk9]]
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
	~~[[Category: Polymorphism]]~~
	[[Category: Protease]]		[[Category: Protease]]
	[[Category: Secreted]]		[[Category: Secreted]]
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	[[Category: Transport]]		[[Category: Transport]]
	[[Category: Zymogen]]		[[Category: Zymogen]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 00:33:47 2009''~~